Clinical outcome of HIV/AIDS patients with Mycobacterium spp. disease associated with Cytomegalovirus viremia: a retrospective study.

Clinical outcome of HIV/AIDS patients with Mycobacterium spp. disease associated with Cytomegalovirus viremia: a retrospective study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical outcome of HIV/AIDS patients with Mycobacterium spp. disease associated with Cytomegalovirus viremia: a retrospective study. Xavier A. Flores-Andrade, Amy B. Peralta-Prado, Eduardo Porras-Rosales, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6405843/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The mycobacterial and cytomegalovirus co-infection represents a critical intersection of infectious challenges, especially in the context of people living with human immunodeficiency virus infection. This relation raises questions on whether this co-infection represents increased mortality risk. Elucidating the critical interplay between these two microorganisms is imperative to promptly assess and intervene in the patient’s clinical evolution. The primary endpoint of the present study was to compare the 90-day mortality of immunocompromised people living with HIV/AIDS co-infected with tuberculous and non-tuberculous mycobacteria with and without cytomegalovirus infection. Methods: We conducted a comparative, observational, retrospective study in a tertiary care setting in Mexico City that provides clinical care for people living with HIV. Sociodemographic, clinical, and biochemical data was collected to assess disease evolution, as well as a 90-day retrospective follow-up to evaluate mortality. Statistical analysis was performed to evaluate sample heterogeneity. A survival analysis and Cox proportional hazards analysis were performed to specifically elucidate the effect on mortality of people who presented co-infection of active mycobacterial disease with or without Cytomegalovirus. Results: Mortality between groups failed to demonstrate statistical significance (HR: 1.773, 95%CI: 0.8163, 3.852; p = 0.1479). Aside from the survival analysis, overall mortality at 90-day follow-up was 13%, which is similar to worldwide mortality reported by the World Health Organization (12%). Severe sepsis ( p = 0.032) and multiple organ failure ( p = 0.016) predicted mortality, while immune failure ( p = 0.001) and a positive cytomegalovirus viremia ( p = 0.023) increased risk for disease relapse. Higher body mass index was protective against mortality ( p = 0.042). Conclusions: This study of cytomegalovirus and mycobacterial co-infections in Mexican people living with HIV found no significant mortality or outcome differences by cytomegalovirus viremic status, potentially reflecting effective standard of care. While limited by sample size, the robust model discrimination suggests Cytomegalovirus co-infection may not independently worsen outcomes in well-managed populations. These findings highlight the importance of maintaining optimal antiretroviral therapy and mycobacterial treatment coverage in resource-appropriate settings. Cytomegalovirus Mycobacterium HIV AIDS Figures Figure 1 Figure 2 Figure 9 Background Mycobacteria are one of the oldest pathogens in history that can cause infection in humans, presenting typically with lung disease characterized by the appearance of granulomas and inflammation. In 2023, approximately 10.8 million people fell ill with tuberculous mycobacterial (TM) disease, from which 1.25 million died ( 1 ). An estimated 1.7 billion people live with latent TM infection, usually presenting symptoms in the first 12 to 18 months. However, reactivation can occur years after ( 2 ). In 2023 the World Health Organization (WHO) estimated that 84% of notified people with TM disease were known to be positive to human immunodeficiency virus (HIV) ( 3 ). Regarding non-tuberculous mycobacteria (NTM), reports exhibit considerable variability. A study in the United States showed a prevalence of 1.4 to 6.6 cases per 100,000 individuals, while another study in England presented 4 to 6.1 cases per 100,000 individuals. However, since then, incidence has been increasing ( 4 , 5 ). Tuberculous mycobacteria accounts for one of the most frequent opportunistic infections in people living with HIV (PLWH), with 26-times greater risk compared with HIV-negative people ( 6 ). This risk is associated with the continuous depletion of CD4 + T lymphocytes (CD4), particularly the Th1, Th17, and Th22 subsets. This depletion leads to reduced production of cytokines required for the activation of macrophages into their M1 state, consequently diminishing their ability to phagocytize mycobacteria. Notably, low concentrations of interferon-γ, decreases the capacity of macrophages to eliminate mycobacteria through autophagy and the synthesis of nitric oxide and other antimicrobial peptides. Additionally, the HIV-1 accessory protein Nef reduces macrophage's phagocytic capability by inhibiting AP1-mediated endosomal recycling necessary for the formation of nascent phagosomes. Although autophagosome assembly increases in HIV-1-infected macrophages, and their maturation and clearance function by fusion with lysosomes is attenuated due to the interaction of HIV-1 Nef with the autophagy-related protein beclin 1 ( 6 , 7 ). HIV co-infection is the largest single risk factor for developing active disease caused by TM, and at the same time, TM disease leads to increased viral replication, contributing to HIV disease progression. Moreover, Mycobacterial disease has recently acquired greater importance due to the emergence of drug-resistant mycobacteria, approximately accounting for 400 thousand people who developed multi-drug resistance ( 1 ). HIV coinfection alters TM disease phenotype, as it is influenced by the CD4 count. This generates a wide range of clinical manifestations, presenting as classic TM disease or with atypical manifestations dependent on the immunocompromised state, making diagnosis challenging ( 8 – 10 ). In the last decade, the use of new techniques for the diagnosis of TM and NTM has increased significantly, especially in the field of molecular biology. However, the timely diagnosis of diseases caused by mycobacteria continues to be a challenge, since negative microscopies and a high incidence of extrapulmonary disease have been observed with increasing frequency. This is important as clinicians frequently require the use of invasive procedures to obtain lung biopsies or bronchoalveolar lavage samples to establish the correct diagnosis ( 11 ). One of the most used diagnostic tests for TM, is the GeneXpert technology as it counts with a similar specificity as the mycobacterial culture, but higher sensitivity. However, the ability of GeneXpert to detect resistance to certain drugs, gave superiority to the GeneXpert technology ( 12 ). Similar to TM disease, prior to the introduction of antiretroviral therapy (ART), up to 43% of people with acquired immunodeficiency syndrome (AIDS) were reported to be co-infected with disseminated NTM, especially those with severe immunodeficiency. In the ART era, the most common NTM is Mycobacterium avium-intracellulare complex (MAC), which accounts for 71% of pulmonary NTM infections in Australia, followed by 54% in Asia, 52% in North America, 51% in South Africa, 37% in Europe and 31% in South America ( 13 ). In contrast, disseminated NTM incidence has been decreasing since ART introduction, to 2.5 cases per 1,000 person-years ( 14 ). On the other hand, prior to the introduction of ART, Cytomegalovirus (CMV) seropositivity was higher than 90% in the general adult population, according to studies conducted in South America, Asia, and Africa ( 15 – 17 ). Reactivation has been related to worse clinical outcomes, associated with cardiovascular diseases, greater immunosenescence and altered mental status of co-infected individuals ( 15 ). CMV disease occurs in more than 30% of PLWH in high-income countries ( 16 ). However, despite multiple interventions, a threat persists for people with advanced immunosuppression even in the ART era. Few studies have examined TM and NTM with CMV disease. A study by Ward et al. found that CMV viremia presented a trend towards increased mortality in PLWH co-infected with TM, particularly in people older than 36 years ( 18 ). Since there is limited information on whether CMV viremia contributes to worse clinical outcomes, the primary endpoint of the present study was to compare the 90-day mortality of immunocompromised PLWH co-infected with TM or NTM with and without CMV infection. The secondary objectives were to describe and compare the sociodemographic, clinical characteristics, biochemical and microbiological parameters, and immunovirological dynamics of PLWH co-infected with TM or NTM with and without CMV infection. Methods We conducted a comparative, observational, retrospective study in a tertiary care setting in Mexico City that provides clinical multidisciplinary care to PLWH. Records of people diagnosed with HIV confirmed by enzyme-linked immunosorbent assay (ELISA) and presenting with an active infection with TM or NTM confirmed by culture, smear or GeneXpert, or suspected by clinical and/or radiological manifestations, and who had been hospitalized between 2016 and 2022 at the Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), in México City, Mexico, were reviewed. Only adults diagnosed with HIV and active mycobacterial infection were included and divided into two groups. The first group included people with detectable CMV viral load (VL) in peripheral blood, and the second group included people with undetectable CMV VL in peripheral blood. CMV VL was measured using the ELITe InGenius Waste Box (Ref. F2102-000, ELITechGroup S. p. A., Turin, Italy) with the CMV ELITe MGB Kit (Ref. RTK015PLD, ELITechGroup S. p. A., Turin, Italy). Incomplete records and records of people who were transferred to other institutions were excluded. Sociodemographic data including gender, age, weight, and height, tobacco, alcohol, and drug consumption were documented, as well as chronic degenerative diseases and sexual preferences. Biochemical tests performed at admission included: leukocytes, hemoglobin, platelets, glucose, creatinine, sodium, albumin, total bilirubin, transaminases, lactate dehydrogenase, and alkaline phosphatase. CD4 count, VL for HIV and CMV were also collected at time of admission and 90 days after. Active mycobacterial infection was confirmed microbiologically by a positive culture, smear or GeneXpert in the biopsy from the affected site. Suspected TM or NTM disease was defined as the presence of clinical (dyspnea, cough, weight loss, diaphoresis, fever, and/or difficulty breathing) and radiological (lung consolidations, cavities, and/or nodules) manifestations plus having clinical improvement after starting therapy. Mycobacterial species identification was performed after culture isolation of the mycobacteria with the GenoType MTBDRplus VER.2.0. (Hain Lifescience GmbH, Neheren, Germany). Furthermore, resistance profile was performed with the BD Kit, BD BACTEC MGIT 960 SIRE (Ref. 245123, Becton, Dickinson and Company, Baltimore, USA), to evaluate TM resistance prevalence and differences between groups. Mycobacterial disease confirmation site was also documented. All participants received proper mycobacterial therapy according to the clinical and microbiological evaluation, as well as CMV therapy with ganciclovir or valganciclovir if end-organ damage was documented or if the attending physician considered it necessary at the time. Clinical data was collected from clinical records, especially clinical manifestations associated with mycobacterial disease such as fever, dyspnea, cough, headache, diarrhea, and weight loss. Furthermore, other physical findings (hepatomegaly, splenomegaly, etc.) and syndromes during hospitalization (sepsis, septic shock, severe acute respiratory failure, etc.) were documented for analysis. Discharge diagnoses paying special attention to the presence of other opportunistic infections such as Candida spp., Kaposi Sarcoma, Pneumocystis jirovecii pneumonia (PCP), and Hepatitis B and C viruses, etc., were obtained, as well as the duration in hospital stay, development of immune reconstitution inflammatory syndrome (IRIS), the type of IRIS, treatment failure, relapse, and death up to 90 days after admission. The planned statistical analysis for this study was to compare both groups to evaluate the impact in mortality caused by CMV co-infection with TM or NTM disease in PLWH. Baseline sociodemographic characteristics, biochemical parameters, immunovirological dynamics, and microbiological characteristics were described as a total and by group and compared through statistical tests such as chi square test of independence or Fisher’s exact test for qualitative variables (as appropriate), or Student’s T with or without Welch correction (according to Levene test for variance equality) or Mann-Whitney U tests (as appropriate) for quantitative variables. A survival analysis and Cox proportional hazards analysis were performed to specifically elucidate the effect on mortality of people who presented co-infection of active mycobacterial disease with or without CMV. Kaplan-Meier curves were used to graphically demonstrate the evolution of participants through a 90-day follow-up using mortality as the outcome of interest. The Cox proportional hazard models were constructed using a stepwise selection process to properly identify the optimal model based on Akaike’s Information Criterion (AIC). All relevant covariates were retained in the final multivariable models regardless of statistical significance. Model assumptions were thoroughly validated through examination of Martingale residuals to assess the functional form of continuous variables and detect potential outliers, along with Schoenfeld global and covariate-specific tests to verify proportional hazards assumptions. REDCap program version 12.4.6–2022 from Vanderbilt University was used for data collection and storage. Result tables were built using Microsoft Excel version 2311. Data analysis was performed using SPSS program version 20; however, the survival analysis was performed using RStudio 2024.12.0 + 467 "Kousa Dogwood" and the set of packages “tidyverse”, “survival”, “survminer”, and “MASS”. Data visualization was carried out using GraphPad Prism 8.0.2.263. The STROBE guidelines were used to assess manuscript completion and quality of the presented work ( 19 ). STROBE checklist can be found in Supplementary appendix S1. The study was approved by the INER research and ethics in research committee with approval number C34-22 according to national regulations (“Ley General de Salud en Materia de Investigación” and the NOM-012-SSA3-2012, which establishes the criteria for the execution of research projects for health in human beings) and international regulations (Declaration of Helsinki, according to its last assembly in Fortaleza, Brazil 2013). Results From the total cohort of people presenting with mycobacterial disease, 215 individuals with HIV infection and mycobacterial infection were found to be hospitalized during the study period, of which 18 records were incomplete and two were not found, leaving a total of 195 participants with complete records. Of the total participants included, 86 (44%) presented a positive CMV viremia and 109 (56%) presented with a negative CMV viremia (Figure 1). A total of 195 individuals were included, of which 163 (84%) were cisgender men, 28 (14%) were cisgender women, and 4 (2%) were transgender women. The mean age of the complete sample was 35.7 (±9.5). The body mass index (BMI) was calculated with a mean of 19.26 (±3.54). In the total sample, 97 (50%) participants had regular tobacco consumption, 90 (46%) consumed alcohol regularly, and 44 (23%) consumed drugs. Only 2 (1%) of the participants had type 2 diabetes and 6 (3%) presented with non-viral hepatopathy. Of the total sample, 76 (39%) were homosexual, 55 (28%) were bisexual and 64 (33%) were heterosexual. Of all participants, 74 (38%) had already received ART in the past from which 54 (28%) were hospitalized due to IRIS, and 20 (16%) abandoned ART. The most common clinical manifestations were fever and dyspnea in both groups. However, the prevalence was higher in the CMV-negative group ( p = 0.027 and p = 0.005 respectively). Regarding concomitant opportunistic infections, the most prevalent was mucocutaneous Candida spp. infection, presented by 65 (33%) participants, followed by PCP (25%), Kaposi sarcoma (11%), and histoplasmosis (7%). The baseline and clinical characteristics of the participants are shown in Table 1. Table 1. Sociodemographic and clinical characteristics at baseline Characteristic Total CMV viremia No CMV viremia p n = 195 n = 86 n = 109 Gender – no. (%)* Men 163 (84) 72 (84) 91 (83) 0.721 Woman 28 (14) 13 (15) 15 (14) Trans Woman 4 (2) 1 (1) 3 (3) Mean age (SD) – yr** 35.75 (9.51) 37.06 (9.03) 34.72 (9.79) 0.089 Mean BMI (SD) – kg/m 2 ** 19.26 (3.54) 19.27 (3.67) 19.26 (3.44) 0.986 Habits and comorbidities Tabaquism – no. (%)* 97 (50) 44 (51) 53 (49) 0.725 Etilism – no. (%)* 90 (46) 40 (47) 50 (46) 0.929 Drug use – no. (%)* 44 (23) 20 (23) 24 (22) 0.837 Diabetes Mellitus – no. (%)* 2 (1) 0 (0) 2 (2) 0.207 Non-viral hepatopathy – no. (%)* 6 (3) 3 (3) 3 (3) 0.768 Sexual preferences – no. (%)* Bisexual 55 (28) 25 (29) 30 (28) 0.552 Heterosexual 64 (33) 31 (36) 33 (30) Homosexual 76 (39) 30 (35) 30 (28) Previous ART use – no. (%)* 74 (38) 39 (45) 35 (32) 0.059 Hospitalization and clinical manifestations SOFA** 2 (1-3) 2 (1-3) 2 (2-3) 0.333 APACHE-II** 10 (8-12) 9 (8-12) 10 (8-12) 0.488 Fever – no. (%)* 189 (97) 81 (94) 108 (99) 0.027 Dyspnea – no. (%)* 136 (70) 51 (59) 85 (78) 0.005 Cough – no. (%)* 155 (80) 63 (73) 92 (84) 0.056 Headache – no. (%)* 63 (32) 23 (27) 40 (37) 0.14 Diarrhea – no. (%)* 85 (44) 37 (43) 48 (44) 0.887 Weight loss – no. (%)* 166 (85) 71 (83) 95 (87) 0.37 Glasgow coma scale – no. (%)* 15 (15-15) 15 (15-15) 15 (15-15) 0.615 Lymphadenopathies – no. (%)* 67 (34) 29 (34) 38 (35) 0.965 Hepatomegaly – no. (%)* 77 (40) 32 (37) 45 (41) 0.827 Esplenomegaly – no. (%)* 44 (23) 24 (28) 20 (18) 0.257 Sepsis – no. (%)* 56 (29) 29 (34) 27 (25) 0.376 Septic shock – no. (%)* 27 (14) 17 (20) 10 (9) 0.1 ARDS – no. (%)* 29 (15) 15 (17) 14 (13) 0.633 Multiple organic failure – no. (%)* 27 (14) 16 (19) 11 (10) 0.184 Simultaneous opportunistic and other infections Mucocutaneous candidiasis – no. (%)* 65 (33) 32 (37) 33 (30) 0.308 Coccidioidomycosis – no. (%)* 5 (3) 3 (3) 2 (2) 0.389 Cryptococcosis – no. (%)* 4 (2) 2 (2) 2 (2) 0.596 Cryptosporidium disease – no. (%)* 4 (2) 2 (2) 2 (2) 0.596 HIV encephalopathy – no. (%)* 5 (3) 1 (1) 4 (4) 0.267 Histoplasmosis – no. (%)* 13 (7) 3 (3) 10 (9) 0.114 Kaposi sarcoma – no. (%)* 21 (11) 11 (13) 10 (9) 0.419 Pneumocystis jirovecii pneumonia – no. (%)* 49 (25) 23 (27) 26 (24) 0.644 Salmonella disease – no. (%)* 3 (2) 2 (2) 1 (1) 0.411 Hepatitis B virus – no. (%)* 7 (4) 5 (6) 2 (2) 0.137 Hepatitis C virus – no. (%)* 5 (3) 2 (2) 3 (3) 0.611 Table 1. Sociodemographic and clinical characteristics. *Chi square test of independence or Fisher’s exact test was performed accordingly. **Student’s T (with Welch correction according to Levene test for variance equality) or Mann-Whitney U test was performed accordingly. Abbreviations: CMV: cytomegalovirus, SD: standard deviation, BMI: body mass index, ART: antiretroviral therapy, ARDS: acute respiratory distress syndrome. Biochemical parameters upon admission did not demonstrate significant differences between both groups, except for the total leukocyte count, which was higher in the CMV-negative viremia group ( p = 0.045). The biochemical parameters at admission can be found in Supplementary appendix S2. At baseline, HIV VL was similar between both groups ( p = 0.982), presenting a median of 70,616 copies/mL (IQR = 262-620,661). Baseline CD4 counts were very similar between groups ( p = 0.895) with a median of 42 cells/μL (IQR = 18-106). At 90-day after admission, HIV viral suppression (<50 copies/mL) was achieved by 72 (37%) of the total sample, 33 (38%) in the CMV positive group vs 39 (36%) in the CMV negative group ( p = 0.709). A total of 108 (55%) presented with a HIV VL lower than 200 copies/ML, 46 (53%) in the CMV group vs 62 (57%) in the CMV negative group ( p = 0.636). CD4 T cell reconstitution was achieved by both groups similarly with 31 (16%) with a CD4 count higher than 200 cells/mL, 15 (17%) in the CMV positive group vs 16 (15%) in the CMV negative group ( p = 0.600). Both groups recovered CD4 similarly at day 90 after admission ( p = 0.821). Immunovirological dynamics at baseline and at 90-day follow-up are shown in Table 2. Table 2. Immunovirological dynamics Characteristic Total CMV viremia No CMV viremia p n = 195 n = 86 n = 109 Admission HIV VL – (copies/mL)* 70,616 (262-620661) 123,914 (148-622,889) 51,619 (353-642,412) 0.982 HIV VL log – (copies/mL) * 4.23 (2.4-5.7) 5.09 (2.1-5.7) 4.71 (2.5-5.8) 0.919 CD4 – (cells/mL) * 42 (18-106) 43 (14-118) 42 (19-91) 0.895 CD4 – (%)* 8 (4-15) 8 (4-15) 8 (4-15) 0.935 Day 90 HIV VL – (copies/mL) * 65 (40 - 635) 56 (40 -565) 75 (40-715) 0.137 < 200 – no. (%)* 108 (55) 46 (53) 62 (57) 0.636 200 – no. (%)* 31 (16) 15 (17) 16 (15) 0.600 CD4 – (%)* 11 (6-17) 10 (5-16) 13 (6-17) 0.210 Table 2. Immunovirological dynamics. *Student’s T (with Welch correction according to Levene test for variance equality) or Mann-Whitney U test was performed accordingly. Abbreviations: CMV: cytomegalovirus, VL: viral load, CD4: CD4 T lymphocytes, Log: logarithmic. Regarding microbiological isolation, 139 (71%) participants presented disease caused by TM, of which 139 (71%) were identified as M. tuberculosis. NTM were isolated in 34 (17%) participants, of which 2 (1%) were M. simiae and 32 (16%) were identified as MAC , the rest were not identified or were not isolated microbiologically and therefore were considered as suspected TM or NTM disease. Mycobacterium tuberculosis (MTB) resistance phenotype in this cohort was mostly represented by pan-susceptible MTB in 115 (59%), followed by 10 (5%) extensively resistant MTB, 7 (4%) multidrug resistant MTB, monoresistant MTB (mainly to isoniazid) in 4 (2%) participants, and the remaining study participants did not undergo MTB drug susceptibility testing. Furthermore, diagnosis by GeneXpert was performed and resulted positive in 121 (62%) participants, of which 15 (8%) had rifampicin resistance. GeneXpert confirmation was higher in the no CMV viremia group (56% vs 67%, p = 0.041). Regarding disease presentation, disseminated disease was the most common, presenting in 108 (55%), followed by extrapulmonary disease presented by 51 (26%) participants and lastly pulmonary disease in 36 (18%) participants. Extrapulmonary affected sites were mainly lymph nodes (18%), followed by central nervous system (11%). Microbiologic characteristics are shown in Table 3. Table 3. Microbiological characteristics Characteristic Total CMV viremia No CMV viremia p n = 195 n = 86 n = 109 Mycobacterial disease confirmation Microbiological confirmation – no. (%)* 176 (90) 77 (90) 99 (91) 0.763 Smear – no. (%)* 67 (34) 25 (29) 42(39) 0.167 MTB Culture – no. (%)* Pan-susceptible MTB 115 (59) 53 (62) 62 (57) 0.503 Monoresistant MTB 4 (2) 1 (1) 3 (3) 0.436 MDR MTB 7 (4) 1 (1) 6 (6) 0.105 XDR MTB 10 (5) 3 (3) 7 (6) 0.356 Mycobacteria species Mycobacterium tuberculosis – no. (%)* 139 (71) 58 (67) 81 (74) 0.364 Mycobacterium avium complex – no. (%)* 32 (16) 17 (20) 15 (14) Mycobacterium. simiae – no. (%)* 2 (1) 0 (0) 2 (2) Not identified – no. (%)* 1 (1) 0 (0) 1 (1) Not isolated – no. (%)* 21 (11) 11 (13) 10 (9) GeneXpert confirmation Positive GeneXpert – no. (%)* 121 (62) 48 (56) 73 (67) 0.041 Rifampicin resistance – no. (%)* 15 (8) 3 (3) 12 (11) 0.073 Mycobacterial disease confirmation site Pulmonary – no. (%)* 36 (18) 9 (10) 27 (25) 0.008 Disseminated – no. (%)* 108 (55) 54 (63) 54 (50) 0.044 Extrapulmonary – no. (%)* 51 (26) 23 (27) 28 (26) 0.498 Central Nervous System 21 (11) 10 (12) 11 (10) 0.819 Lymphatic ganglia 35 (18) 14 (16) 21 (19) Gastrointestinal 8 (4) 4 (5) 4 (4) Renal 1 (1) 1 (1) 0 (0) Pleural 11 (6) 6 (7) 5 (5) Pericardic 1 (1) 0 (0) 1 (1) Bone 2 (1) 1 (1) 1 (1) Articular 1 (1) 1 (1) 0 (0) Table 3. Microbiological characteristics. *Chi square test of independence or Fisher’s exact test was performed accordingly. Abbreviations: CMV: cytomegalovirus, MTB: Mycobacterium tuberculosis , MDR: multi-drug resistant, XDR: extensively resistant. Study outcomes are delineated in Table 4. Hospital stay duration was similar in both groups (18 vs 17 days, p = 0.326). Moreover, IRIS presentation and type of IRIS were not different ( p = 0.558) between the study groups. Similarly, no significant differences were observed in culture negativity at 90 days (55% vs 59%, p = 0.747), mycobacterial treatment failure (24% for both groups, p = 0.738), or disease relapse (13% vs 4%, p = 0.060). The overall mortality of the study was 13%, showing no differences between both groups (17% vs 10%, p = 0.134). Table 4. Outcomes Characteristic Total CMV viremia No CMV viremia p n = 195 n = 86 n = 109 Hospital stay – days (IQR)** 17 (11-28) 18 (11-28) 17 (13-28) 0.326 IRIS – no. (%)* 54 (28) 22 (26) 32 (29) 0.558 IRIS type – no. (%)* Unmasked 33 (17) 13 (15) 20 (18) 0.817 Paradoxical 21 (11) 9 (10) 12 (11) Culture negativization at 90 days – no. (%)* 111 (57) 47 (55) 64 (59) 0.747 Mycobacterial treatment failure – no. (%)* 47 (24) 21 (24) 26 (24) 0.738 Relapse – no. (%)* 15 (8) 11 (13) 4 (4) 0.060 Deaths – no. (%)* 26 (13) 15 (17) 11 (10) 0.134 Table 4. Outcomes. *Chi square test of independence or Fisher’s exact test was performed accordingly. **Student’s T (with Levene test for variance equality) or Mann-Whitney U test was performed accordingly. Abbreviations: CMV: cytomegalovirus, IQR: interquartile range, IRIS: immune reconstitution inflammatory syndrome. In the survival analysis at 90-day follow-up, a total of 195 participants were included, of which 26 died. Divided by groups, we observed that 11 participants without CMV viremia died compared to 15 participants with CMV viremia. The Kaplan-Meier curves and survival tables are presented in Figure 2 and Table 5. In addition, the comparison between groups was carried out with the Log Rank test (Mantel-Cox) without showing significant differences (Chi square = 2.161, p = 0.142). Furthermore, the hazard ratio of mortality in individuals presenting with active mycobacterial disease co-infected with CMV in relation with the individuals with only mycobacterial disease did not present statistical significance (HR = 1.773, 95% CI: 0.8163-3.852). Table 5. Number of patients at risk by day Group Number of patients No CMV viremia 109 105 95 94 89 89 82 20 0 CMV viremia 86 82 77 71 70 67 67 9 0 Days 0 10 20 30 40 50 60 70 80 Table 5. Outcomes. Abbreviations: CMV: cytomegalovirus. Finally, the Cox proportional hazard analysis (Table 6) revealed several significant predictors of survival outcomes. Participants with severe sepsis had 3.35 times higher mortality risk (95% CI:1.11-10.11; p = 0.032), while those with multiple organ failure showed 3.18-fold increased risk (95% CI: 1.24-8.19; p = 0.016). Higher BMI was observed as a protective factor (HR = 0.84 per unit; 95% CI: 0.72-0.99; p = 0.042). CD4 count showed borderline significance as a protective factor (HR = 0.99 per cell; 95% CI 0.97-1.00; p = 0.058). Age, alcohol consumption, multiple opportunistic infections, HIV VL and CMV group status did not show statistically significant associations. The model demonstrated excellent discriminative ability (concordance = 0.869) and overall significance (likelihood ratio test = p <0.0001). Similarly, we conducted a Cox regression analysis of mycobacterial disease relapse risk (Table 6) in which we identified several significant predictors. Immune failure (HR = 6.70; 95% CI: 2.09-21.52; p = 0.001) was strongly associated with increased relapse risk. Current smokers presented 3.45-fold increased risk (95% CI: 1.02-11.68; p = 0.046), as did participants in the CMV group (HR = 4.14; 95% CI: 1.22-14.09; p = 0.023). Hospitalization length showed no significance (HR = 0.97 per day; p = 0.154), similar to IRIS presentation that showed a non-significant reduction in relapse risk (HR = 0.21; p = 0.138). Similar to the survival model, this model had excellent discrimination (concordance = 0.863) and overall significance (likelihood ratio test <0.0001). Table 6. Comparative Multivariable Cox Regression Analyses for Mortality and Relapse Outcomes Predictor Level Mortality Analysis (N = 195, Events = 26) Relapse Analysis (N = 183, Events = 15) aHR (95% CI) p aHR (95% CI) p Demographic Factors Age per year 1.02 (0.99-1.06) 0.199 - - BMI per unit 0.84 (0.72-0.99) 0.042 - - Clinical Factors Smoking status Yes - - 3.45 (1.02-11.68) 0.046 Hospital days per day - - 0.97 (0.93-1.01) 0.154 Severe sepsis Yes 3.35 (1.11-10.11) 0.032 - - Multiple organ failure Yes 3.18 (1.24-8.19) 0.016 - - IRIS Yes - - 0.21 (0.03-1.65) 0.138 Immune failure Yes - - 6.70 (2.09-21.52) 0.001 Multiple OI Yes 1.70 (0.62-4.61) 0.301 - - HIV-Related Factors HIV viral load (log) per log 1.02 (0.80-1.30) 0.9 - - CD4 count per cell 0.99 (0.97-1.00) 0.058* - - CMV group CMV 1.29 (0.56-2.95) 0.554 4.14 (1.22-14.09) 0.023 Table 6. Comparative Multivariable Cox Regression Analyses for Mortality and Relapse Outcomes. Model Fit Statistics: Mortality: Concordance = 0.869, LR test p <0.0001, Relapse: Concordance = 0.863, LR test p <0.0001. Abbreviations: aHR: adjusted Hazard Ratio; CI: Confidence Interval, OI: Opportunistic infections; IRIS: Immune Reconstitution Inflammatory Syndrome, CMV: Cytomegalovirus. *Borderline significance (p<0.1). Discussion In this study, the baseline characteristics of both groups demonstrated significant similarities, ensuring a homogeneous and comparable sample. Immunovirological dynamics were comparable between the groups, with no statistically significant differences observed in HIV viral suppression at the 90-day follow-up, as assessed using thresholds of <200 and <50 copies/mL. These results are a reflection of the profound baseline immunosuppression and high HIV VL at admission. Most individuals presented with advanced HIV, which is an imperative factor known to delay virological response. Similarly, CD4 cell counts did not differ significantly between the groups by day 90 post-admission. These findings suggest that CMV viremia occurring alongside active mycobacterial infection is not associated with delayed HIV viral suppression or impaired immune recovery. This aligns with existing evidence indicating that individuals with opportunistic infections and advanced immunosuppression often exhibit prolonged delays in achieving viral suppression and immune reconstitution (20). Overall mortality in this study (13%) was consistent with the one reported by the WHO in the Global Tuberculosis Report 2024 (12%) (1). While this cohort did not demonstrate CMV co-infection as an independent prognostic marker for mortality in PLWH and active mycobacterial disease, our analysis revealed CMV viremia as a significant predictor of mycobacterial disease relapse. This may reflect our center’s standardized protocol of rapid CMV PCR testing and end-organ disease identification, and preemptive antiviral initiation, which likely mitigated systemic CMV effects while insufficiently preventing its localized immunomodulatory impact on mycobacterial control. This observation aligns with the known immunomodulatory effects of CMV in advanced immunosuppression. Mycobacterial control fundamentally requires a robust Th1 response (mediated by IFN-γ, TNF-α, and IL-12) (21). However, during CMV coinfection, persistent interferon-alpha (IFN-α) production by plasmacytoid dendritic cells disrupts Th1 polarization through IL-12 signaling suppression (22). Concurrently, CMV drives clonal expansion of terminally differentiated CD8 T cells, depleting resources for mycobacteria-specific Th1 responses (23). All together, these mechanisms impair macrophage activation and granuloma integrity, creating a permissive environment for mycobacterial dissemination and worse clinical outcomes, even in the absence of overt CMV end-organ disease, which can be seen in the differences in the presentation of the mycobacterial disease between groups (24). Furthermore, CMV reactivation is associated with an increased mortality among PLWH with severe immunodeficiency. This has been demonstrated throughout several clinical settings which found that CMV viremia predicts higher mortality risk even with prompt ART initiation (25). Notably, in our cohort (where ART initiation occurred without delays) this association persisted, suggesting CMV’s pathogenic role is an important factor beyond delays in ART. Regarding clinical manifestations, interestingly, the CMV-positive group exhibited significantly lower rates of fever compared to the CMV-negative group. While this can be counterintuitive, this finding is supported by the emerging evidence on how inflammatory responses are blunted in people with advanced immunosuppression driven by CD4 depletion which can impair pyrogenic cytokine production, CMV-encoded immunomodulators like UL83 which can directly suppress IL-1β and IL-6, and CMV-driven IL-10 overexpression which systemically attenuate febrile responses (26). This paradoxical absence of fever underscores the importance of considering CMV coinfection even in afebrile people with advanced HIV. Moreover, the low frequency of dyspnea among the CMV-infected group prompted further investigation to evaluate if this represented a true biological effect or confounding by mycobacterial disease localization. We conducted a focused subanalysis of participants with pulmonary mycobacterial disease, in which dyspnea prevalence was no longer significant ( p = 0.557, Supplementary Appendix S3) suggesting that the initial observation may have reflected differential distribution of extrapulmonary involvement rather than a direct CMV-mediated effect on respiratory symptoms. This highlights the importance of accounting for disease localization when evaluating clinical manifestations in immunocompromised hosts with multiple concurrent infections. GeneXpert diagnostic performance for mycobacterial disease varies depending on the level of immunosuppression, clinical presentation, and bacillary load (27). In our cohort, the CMV-negative group showed a higher incidence of pulmonary mycobacterial disease, which may explain their increased GeneXpert positivity rates, as pulmonary forms typically have higher bacillary loads. Conversely, the CMV-positive group demonstrated greater prevalence of disseminated disease and potentially more paucibacillary presentation, which are features associated with reduced GeneXpert sensitivity and specificity that may reflect their advanced immunosuppression. This pattern suggests profound T-cell dysfunction facilitating mycobacterial dissemination, and CMV-mediated endothelial damage potentially enhancing systemic spread (28). Together, these factors may create a diagnostic paradox where people with greatest mycobacterial disease burden have lower GeneXpert positivity due to bacillary dissemination and pauci-bacillary presentations. Our findings reveal different risk profiles for mortality and relapse that highlight the critical role of organ dysfunction in mortality (sepsis and multiple organ dysfunction) and immune dysregulation in disease relapse (immune failure). The protective effect of higher BMI against mortality aligns with the obesity paradox observed in some other chronic diseases (29). Clinically, these results advocate for 1) aggressive sepsis management in high-risk people, particularly those with low BMI, 2) enhanced monitoring for CMV-positive individuals or those with immune failure, and 3) careful documentation to distinguish relapse events to prevent complications. Strengths and limitations This study is limited by its own design as it is retrospective in nature which introduces potential unmeasured confounders. Some of the key data limitations include the lack of CMV seroprevalence data (which prevents assessment of CMV reactivation or new infection), absence of detailed documentation regarding sample types used for GeneXpert testing, and missing longitudinal measurements such as serial CMV serology, VL monitoring, and mycobacterial therapy adherence, which are critical variables for assessing viremia persistence, end-organ disease progression, and treatment efficacy over time. Additionally, the small event numbers may limit statistical power. However, the study demonstrates robust model discrimination supporting its clinical utility. Importantly, it provides the first investigation into the relationship between active mycobacterial co-infection and CMV in PLWH within the Mexican population, which is important as it addresses a key knowledge gap. Future research should prioritize prospective designs to properly control for confounding variables and incorporate CMV-specific immune pathway analysis. The development of dual-outcome prediction models could further refine personalized monitoring strategies. These results highlight the need for distinct clinical approaches to mortality prevention versus relapse mitigation in this high-risk group. Conclusions This study, as far as we know, represents the first investigation of CMV and mycobacterial co-infection dynamics in PLWH from the Mexican population. While our analysis did not demonstrate statistically significant differences in mortality or secondary outcomes (including IRIS presentation, treatment failure or disease relapse, between individuals with and without CMV co-infection, several important considerations emerge from our findings. The lack of observed association may reflect the effectiveness of current standard-of-care practices in our clinical setting, particularly regarding immune reconstitution and opportunistic infection management. However, important study limitations must be acknowledged as discussed earlier. Notwithstanding these limitations, our results demonstrate robust model discrimination that supports the clinical relevance of our analytical approach. The findings suggest that in resource-appropriate settings with adequate ART and mycobacterial therapy coverage, CMV co-infection may not independently worsen outcomes in this population. Abbreviations TM: Tuberculous mycobacterial. WHO: World Health Organization. HIV: Human Immunodeficiency Virus. NTM: Non-tuberculous mycobacteria. PLWH: People living with human immunodeficiency virus. CD4: CD4+ T lymphocytes. ART: Antiretroviral therapy. AIDS: Acquired immunodeficiency syndrome. MAC: Mycobacterium avium-intracellulare complex. CMV: Cytomegalovirus. ELISA: Enzyme-linked immunosorbent assay. INER: Instituto Nacional de Enfermedades Respiratorias. VL: Viral load. PCP: Pneumocystis jirovecii pneumonia. IRIS: Immune reconstitution inflammatory syndrome. AIC: Akaike’s Information Criterion. BMI: Body mass index. ARDS: Acute respiratory distress syndrome. MTB: Mycobacterium tuberculosis. MDR: Multi-drug resistant. XDR: Extensively resistant. HR: Hazard ratio. CI: Confidence interval. OI: opportunistic infection. Declarations Ethics approval and consent to participate: The research and ethics committee of the Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" reviewed and approved the preparation and development of this retrospective study with acceptance number C34-22, as it adhered to the national regulations (“Ley General de Salud en Materia de Investigación” and the NOM-012-SSA3-2012, which establishes the criteria for the execution of research projects for health in human beings) and the international regulations (Declaration of Helsinki, according to its last assembly in Fortaleza, Brazil 2013). Likewise, a waiver of informed consent was approved by both research and ethics committee. Clinical Trial: Not applicable. Consent for publication: The study did not present any individual-level identifiable data (including medical images, personal details, or multimedia records) requiring specific consent for publication. Availability of data and materials: All data generated and analyzed during the present study were included in the file titled “Supplementary_Raw Data”. Competing of interests: All authors declare that there is no conflict of interest. Xavier A. Flores-Andrade None Amy B. Peralta-Prado None Eduardo Porras-Rosales None Andrea Cárdenas-Ortega None Víctor H. Ahumada-Topete None Santiago Ávila-Ríos None Funding: This work was supported by funds from the Mexican Government (Programa Presupuestal P016; Anexo 13 del Decreto del Presupuesto de Egresos de la Federación). The funders had no role in the study design, data collection and analysis, publication decisions, or manuscript preparation. Author contributions and information: 1. Corresponding author: XAFA, MD: Author and responsible for: Conceptualization, data curation, formal analysis, investigation, methodology, visualization, writing, review, and editing of the original manuscript. Mail: [email protected] ORCID: 0000-0003-1529-7276. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, Mexico. 2. ABPP, MD, MSc: Author and responsible for: Data curation, formal analysis, methodology, project administration, supervision, review and editing of the original draft. Mail: [email protected] , ORCID: 0000-0002-6379-9134. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, Mexico. 3. EPR, MD: Author and responsible for: Conceptualization, data curation, investigation, methodology. Mail: [email protected] , OCRID: 0000-0003-2589-8497. Hospital “Manolo Morales”, Managua, Nicaragua. 4. ACO, MD: Author and responsible for: Conceptualization, data curation, investigation, methodology. Mail: [email protected] , ORCID: 0009-0000-1827-3283. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, Mexico. 5. VHAT, MD: Responsible for: Project administration, supervision, review and editing of the original manuscript. Mail: [email protected] , ORCID: 0000-0001-9822-3496. Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, Mexico. 6. Santiago Ávila-Rios, PhD: Responsible for: Funding acquisition, project administration, resources, supervision, review and editing of the original draft. Mail: [email protected] , ORCID: 0000-0003-3371-4248. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” (INER), Mexico City, Mexico. Acknowledgements: None. 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Swiss Med Wkly [Internet]. 2015 Dec 13 [cited 2025 Mar 26];145(5152):w14265–w14265. Available from: https://smw.ch/index.php/smw/article/view/2123/3125 Additional Declarations No competing interests reported. Supplementary Files 6.SupplementaryAppendix.docx 7.SupplementaryRawData.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6405843","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":448481195,"identity":"59a5adae-fbf0-4c4d-bec2-06704a17be45","order_by":0,"name":"Xavier A. 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Peralta-Prado","email":"","orcid":"","institution":"Center for Research in Infectious Diseases (CIENI), National Institute of Respiratory Diseases “Ismael Cosío Villegas” (INER)","correspondingAuthor":false,"prefix":"","firstName":"Amy","middleName":"B.","lastName":"Peralta-Prado","suffix":""},{"id":448481197,"identity":"88c63796-699c-47d2-975a-a54122880d78","order_by":2,"name":"Eduardo Porras-Rosales","email":"","orcid":"","institution":"“Manolo Morales” Hospital","correspondingAuthor":false,"prefix":"","firstName":"Eduardo","middleName":"","lastName":"Porras-Rosales","suffix":""},{"id":448481198,"identity":"06c3e1b9-390e-4e86-8ed4-3b56143b24c1","order_by":3,"name":"Andrea Cardenas-Ortega","email":"","orcid":"","institution":"Center for Research in Infectious Diseases (CIENI), National Institute of Respiratory Diseases “Ismael Cosío Villegas” (INER)","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Cardenas-Ortega","suffix":""},{"id":448481199,"identity":"22a1d082-7fbf-4937-8c5f-9693fe78f104","order_by":4,"name":"Víctor H. Ahumada-Topete","email":"","orcid":"","institution":"Instituto Nacional de Enfermedades Respiratorias","correspondingAuthor":false,"prefix":"","firstName":"Víctor","middleName":"H.","lastName":"Ahumada-Topete","suffix":""},{"id":448481200,"identity":"8ff0903f-cd3f-4777-9622-ed5bb7f5c25d","order_by":5,"name":"Santiago Ávila-Ríos","email":"","orcid":"","institution":"Center for Research in Infectious Diseases (CIENI), National Institute of Respiratory Diseases “Ismael Cosío Villegas” (INER)","correspondingAuthor":false,"prefix":"","firstName":"Santiago","middleName":"","lastName":"Ávila-Ríos","suffix":""}],"badges":[],"createdAt":"2025-04-08 18:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6405843/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6405843/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82123941,"identity":"eb320847-16f8-4f4d-9d69-18a1c414def3","added_by":"auto","created_at":"2025-05-07 03:37:07","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":298168,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSTROBE flow diagram.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6405843/v1/c978559e6a280252a5b51f3a.jpeg"},{"id":82120050,"identity":"24df6872-9098-4a72-a255-6e9fbf7a9533","added_by":"auto","created_at":"2025-05-07 03:13:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":15704,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival curves.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLog-rank (Mantel-Cox) test was performed without showing statistical significance.\u003c/p\u003e\n\u003cp\u003eHazard ratio (Mantel-Haenszel) for mortality was greater in the CMV positive group (HR = 1.773, 95% CI: 0.8163, 3.852). Abbreviations: CMV: cytomegalovirus.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6405843/v1/ee3fdff134bc4199446a712b.png"},{"id":82120062,"identity":"8009763c-2538-447c-ab69-89e00dabd303","added_by":"auto","created_at":"2025-05-07 03:13:07","extension":"jpeg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":298168,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSTROBE flow diagram.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6405843/v1/d44aae1ead28cb45e45877a5.jpeg"},{"id":95221355,"identity":"fe67b31b-b4d5-402c-b8d8-fffb5bae8b45","added_by":"auto","created_at":"2025-11-05 16:18:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1871295,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6405843/v1/e4bd3b36-b14c-4829-963c-a9d72e743cc4.pdf"},{"id":82120869,"identity":"efab7f5f-0807-4234-97c1-16899fb72118","added_by":"auto","created_at":"2025-05-07 03:21:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24150,"visible":true,"origin":"","legend":"","description":"","filename":"6.SupplementaryAppendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-6405843/v1/9170498b28ea59d3742d4d2e.docx"},{"id":82120061,"identity":"0f5b4033-6f1c-4ff7-8a5f-1da70276fb35","added_by":"auto","created_at":"2025-05-07 03:13:07","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":100699,"visible":true,"origin":"","legend":"","description":"","filename":"7.SupplementaryRawData.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6405843/v1/d7ffd4117a29fa0a5cf790fe.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical outcome of HIV/AIDS patients with Mycobacterium spp. disease associated with Cytomegalovirus viremia: a retrospective study.","fulltext":[{"header":"Background","content":"\u003cp\u003eMycobacteria are one of the oldest pathogens in history that can cause infection in humans, presenting typically with lung disease characterized by the appearance of granulomas and inflammation. In 2023, approximately 10.8\u0026nbsp;million people fell ill with tuberculous mycobacterial (TM) disease, from which 1.25\u0026nbsp;million died (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). An estimated 1.7\u0026nbsp;billion people live with latent TM infection, usually presenting symptoms in the first 12 to 18 months. However, reactivation can occur years after (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In 2023 the World Health Organization (WHO) estimated that 84% of notified people with TM disease were known to be positive to human immunodeficiency virus (HIV) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Regarding non-tuberculous mycobacteria (NTM), reports exhibit considerable variability. A study in the United States showed a prevalence of 1.4 to 6.6 cases per 100,000 individuals, while another study in England presented 4 to 6.1 cases per 100,000 individuals. However, since then, incidence has been increasing (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTuberculous mycobacteria accounts for one of the most frequent opportunistic infections in people living with HIV (PLWH), with 26-times greater risk compared with HIV-negative people (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This risk is associated with the continuous depletion of CD4\u0026thinsp;+\u0026thinsp;T lymphocytes (CD4), particularly the Th1, Th17, and Th22 subsets. This depletion leads to reduced production of cytokines required for the activation of macrophages into their M1 state, consequently diminishing their ability to phagocytize mycobacteria. Notably, low concentrations of interferon-γ, decreases the capacity of macrophages to eliminate mycobacteria through autophagy and the synthesis of nitric oxide and other antimicrobial peptides. Additionally, the HIV-1 accessory protein Nef reduces macrophage's phagocytic capability by inhibiting AP1-mediated endosomal recycling necessary for the formation of nascent phagosomes. Although autophagosome assembly increases in HIV-1-infected macrophages, and their maturation and clearance function by fusion with lysosomes is attenuated due to the interaction of HIV-1 Nef with the autophagy-related protein beclin 1 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHIV co-infection is the largest single risk factor for developing active disease caused by TM, and at the same time, TM disease leads to increased viral replication, contributing to HIV disease progression. Moreover, Mycobacterial disease has recently acquired greater importance due to the emergence of drug-resistant mycobacteria, approximately accounting for 400 thousand people who developed multi-drug resistance (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHIV coinfection alters TM disease phenotype, as it is influenced by the CD4 count. This generates a wide range of clinical manifestations, presenting as classic TM disease or with atypical manifestations dependent on the immunocompromised state, making diagnosis challenging (\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In the last decade, the use of new techniques for the diagnosis of TM and NTM has increased significantly, especially in the field of molecular biology. However, the timely diagnosis of diseases caused by mycobacteria continues to be a challenge, since negative microscopies and a high incidence of extrapulmonary disease have been observed with increasing frequency. This is important as clinicians frequently require the use of invasive procedures to obtain lung biopsies or bronchoalveolar lavage samples to establish the correct diagnosis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). One of the most used diagnostic tests for TM, is the GeneXpert technology as it counts with a similar specificity as the mycobacterial culture, but higher sensitivity. However, the ability of GeneXpert to detect resistance to certain drugs, gave superiority to the GeneXpert technology (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSimilar to TM disease, prior to the introduction of antiretroviral therapy (ART), up to 43% of people with acquired immunodeficiency syndrome (AIDS) were reported to be co-infected with disseminated NTM, especially those with severe immunodeficiency. In the ART era, the most common NTM is \u003cem\u003eMycobacterium avium-intracellulare complex\u003c/em\u003e (MAC), which accounts for 71% of pulmonary NTM infections in Australia, followed by 54% in Asia, 52% in North America, 51% in South Africa, 37% in Europe and 31% in South America (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In contrast, disseminated NTM incidence has been decreasing since ART introduction, to 2.5 cases per 1,000 person-years (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOn the other hand, prior to the introduction of ART, Cytomegalovirus (CMV) seropositivity was higher than 90% in the general adult population, according to studies conducted in South America, Asia, and Africa (\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Reactivation has been related to worse clinical outcomes, associated with cardiovascular diseases, greater immunosenescence and altered mental status of co-infected individuals (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). CMV disease occurs in more than 30% of PLWH in high-income countries (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, despite multiple interventions, a threat persists for people with advanced immunosuppression even in the ART era. Few studies have examined TM and NTM with CMV disease. A study by Ward et al. found that CMV viremia presented a trend towards increased mortality in PLWH co-infected with TM, particularly in people older than 36 years (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSince there is limited information on whether CMV viremia contributes to worse clinical outcomes, the primary endpoint of the present study was to compare the 90-day mortality of immunocompromised PLWH co-infected with TM or NTM with and without CMV infection. The secondary objectives were to describe and compare the sociodemographic, clinical characteristics, biochemical and microbiological parameters, and immunovirological dynamics of PLWH co-infected with TM or NTM with and without CMV infection.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe conducted a comparative, observational, retrospective study in a tertiary care setting in Mexico City that provides clinical multidisciplinary care to PLWH. Records of people diagnosed with HIV confirmed by enzyme-linked immunosorbent assay (ELISA) and presenting with an active infection with TM or NTM confirmed by culture, smear or GeneXpert, or suspected by clinical and/or radiological manifestations, and who had been hospitalized between 2016 and 2022 at the Instituto Nacional de Enfermedades Respiratorias \u0026ldquo;Ismael Cos\u0026iacute;o Villegas\u0026rdquo; (INER), in M\u0026eacute;xico City, Mexico, were reviewed. Only adults diagnosed with HIV and active mycobacterial infection were included and divided into two groups. The first group included people with detectable CMV viral load (VL) in peripheral blood, and the second group included people with undetectable CMV VL in peripheral blood. CMV VL was measured using the ELITe InGenius Waste Box (Ref. F2102-000, ELITechGroup S. p. A., Turin, Italy) with the CMV ELITe MGB Kit (Ref. RTK015PLD, ELITechGroup S. p. A., Turin, Italy). Incomplete records and records of people who were transferred to other institutions were excluded.\u003c/p\u003e \u003cp\u003eSociodemographic data including gender, age, weight, and height, tobacco, alcohol, and drug consumption were documented, as well as chronic degenerative diseases and sexual preferences. Biochemical tests performed at admission included: leukocytes, hemoglobin, platelets, glucose, creatinine, sodium, albumin, total bilirubin, transaminases, lactate dehydrogenase, and alkaline phosphatase. CD4 count, VL for HIV and CMV were also collected at time of admission and 90 days after.\u003c/p\u003e \u003cp\u003eActive mycobacterial infection was confirmed microbiologically by a positive culture, smear or GeneXpert in the biopsy from the affected site. Suspected TM or NTM disease was defined as the presence of clinical (dyspnea, cough, weight loss, diaphoresis, fever, and/or difficulty breathing) and radiological (lung consolidations, cavities, and/or nodules) manifestations plus having clinical improvement after starting therapy. Mycobacterial species identification was performed after culture isolation of the mycobacteria with the GenoType MTBDRplus VER.2.0. (Hain Lifescience GmbH, Neheren, Germany). Furthermore, resistance profile was performed with the BD Kit, BD BACTEC MGIT 960 SIRE (Ref. 245123, Becton, Dickinson and Company, Baltimore, USA), to evaluate TM resistance prevalence and differences between groups. Mycobacterial disease confirmation site was also documented. All participants received proper mycobacterial therapy according to the clinical and microbiological evaluation, as well as CMV therapy with ganciclovir or valganciclovir if end-organ damage was documented or if the attending physician considered it necessary at the time.\u003c/p\u003e \u003cp\u003eClinical data was collected from clinical records, especially clinical manifestations associated with mycobacterial disease such as fever, dyspnea, cough, headache, diarrhea, and weight loss. Furthermore, other physical findings (hepatomegaly, splenomegaly, etc.) and syndromes during hospitalization (sepsis, septic shock, severe acute respiratory failure, etc.) were documented for analysis.\u003c/p\u003e \u003cp\u003eDischarge diagnoses paying special attention to the presence of other opportunistic infections such as \u003cem\u003eCandida spp., Kaposi\u003c/em\u003e Sarcoma, \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia (PCP), and Hepatitis B and C viruses, etc., were obtained, as well as the duration in hospital stay, development of immune reconstitution inflammatory syndrome (IRIS), the type of IRIS, treatment failure, relapse, and death up to 90 days after admission.\u003c/p\u003e \u003cp\u003eThe planned statistical analysis for this study was to compare both groups to evaluate the impact in mortality caused by CMV co-infection with TM or NTM disease in PLWH. Baseline sociodemographic characteristics, biochemical parameters, immunovirological dynamics, and microbiological characteristics were described as a total and by group and compared through statistical tests such as chi square test of independence or Fisher\u0026rsquo;s exact test for qualitative variables (as appropriate), or Student\u0026rsquo;s T with or without Welch correction (according to Levene test for variance equality) or Mann-Whitney U tests (as appropriate) for quantitative variables. A survival analysis and Cox proportional hazards analysis were performed to specifically elucidate the effect on mortality of people who presented co-infection of active mycobacterial disease with or without CMV. Kaplan-Meier curves were used to graphically demonstrate the evolution of participants through a 90-day follow-up using mortality as the outcome of interest. The Cox proportional hazard models were constructed using a stepwise selection process to properly identify the optimal model based on Akaike\u0026rsquo;s Information Criterion (AIC). All relevant covariates were retained in the final multivariable models regardless of statistical significance. Model assumptions were thoroughly validated through examination of Martingale residuals to assess the functional form of continuous variables and detect potential outliers, along with Schoenfeld global and covariate-specific tests to verify proportional hazards assumptions.\u003c/p\u003e \u003cp\u003eREDCap program version 12.4.6\u0026ndash;2022 from Vanderbilt University was used for data collection and storage. Result tables were built using Microsoft Excel version 2311. Data analysis was performed using SPSS program version 20; however, the survival analysis was performed using RStudio 2024.12.0\u0026thinsp;+\u0026thinsp;467 \"Kousa Dogwood\" and the set of packages \u0026ldquo;tidyverse\u0026rdquo;, \u0026ldquo;survival\u0026rdquo;, \u0026ldquo;survminer\u0026rdquo;, and \u0026ldquo;MASS\u0026rdquo;. Data visualization was carried out using GraphPad Prism 8.0.2.263. The STROBE guidelines were used to assess manuscript completion and quality of the presented work (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). STROBE checklist can be found in Supplementary appendix S1.\u003c/p\u003e \u003cp\u003e The study was approved by the INER research and ethics in research committee with approval number C34-22 according to national regulations (\u0026ldquo;Ley General de Salud en Materia de Investigaci\u0026oacute;n\u0026rdquo; and the NOM-012-SSA3-2012, which establishes the criteria for the execution of research projects for health in human beings) and international regulations (Declaration of Helsinki, according to its last assembly in Fortaleza, Brazil 2013).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFrom the total cohort of people presenting with mycobacterial disease, 215 individuals with HIV infection and mycobacterial infection were found to be hospitalized during the study period, of which 18 records were incomplete and two were not found, leaving a total of 195 participants with complete records. Of the total participants included, 86 (44%) presented a positive CMV viremia and 109 (56%) presented with a negative CMV viremia (Figure 1).\u003c/p\u003e\n\u003cp\u003eA total of 195 individuals were included, of which 163 (84%) were cisgender men, 28 (14%) were cisgender women, and 4 (2%) were transgender women. The mean age of the complete sample was 35.7 (\u0026plusmn;9.5). The body mass index (BMI) was calculated with a mean of 19.26 (\u0026plusmn;3.54). In the total sample, 97 (50%) participants had regular tobacco consumption, 90 (46%) consumed alcohol regularly, and 44 (23%) consumed drugs. Only 2 (1%) of the participants had type 2 diabetes and 6 (3%) presented with non-viral hepatopathy. Of the total sample, 76 (39%) were homosexual, 55 (28%) were bisexual and 64 (33%) were heterosexual. Of all participants, 74 (38%) had already received ART in the past from which 54 (28%) were hospitalized due to IRIS, and 20 (16%) abandoned ART. The most common clinical manifestations were fever and dyspnea in both groups. However, the prevalence was higher in the CMV-negative group (\u003cem\u003ep\u003c/em\u003e = 0.027 and \u003cem\u003ep\u003c/em\u003e = 0.005 respectively).\u003c/p\u003e\n\u003cp\u003eRegarding concomitant opportunistic infections, the most prevalent was mucocutaneous \u003cem\u003eCandida spp.\u003c/em\u003e infection, presented by 65 (33%) participants, followed by PCP (25%), Kaposi sarcoma (11%), and histoplasmosis (7%). The baseline and clinical characteristics of the participants are shown in Table 1.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Sociodemographic and clinical characteristics at baseline\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"599\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003eCMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003eNo CMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003en = 195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003en = 86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003en = 109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eGender \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Men\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e163 (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e72 (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e91 (83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Woman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e28 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e13 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e15 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Trans Woman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eMean age (SD) \u0026ndash; yr**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e35.75 (9.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e37.06 (9.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e34.72 (9.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eMean BMI (SD) \u0026ndash; kg/m\u003csup\u003e2\u003c/sup\u003e**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e19.26 (3.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e19.27 (3.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e19.26 (3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 599px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHabits and comorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eTabaquism \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e97 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e44 (51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e53 (49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eEtilism \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e90 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e40 (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e50 (46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eDrug use \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e44 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e20 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e24 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eDiabetes Mellitus \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eNon-viral hepatopathy \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e6 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eSexual preferences \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bisexual\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e55 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e25 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e30 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.552\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Heterosexual\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e64 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e31 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e33 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Homosexual\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e76 (39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e30 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e30 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003ePrevious ART use \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e74 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e39 (45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e35 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 599px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHospitalization and clinical manifestations\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eSOFA**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e2 (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e2 (1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2 (2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.333\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eAPACHE-II**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e10 (8-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e9 (8-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e10 (8-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.488\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eFever \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e189 (97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e81 (94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e108 (99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eDyspnea \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e136 (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e51 (59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e85 (78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eCough \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e155 (80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e63 (73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e92 (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eHeadache \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e63 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e23 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e40 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eDiarrhea \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e85 (44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e37 (43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e48 (44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.887\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eWeight loss \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e166 (85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e71 (83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e95 (87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eGlasgow coma scale \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e15 (15-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e15 (15-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e15 (15-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.615\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eLymphadenopathies \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e67 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e29 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e38 (35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.965\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eHepatomegaly \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e77 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e32 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e45 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.827\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eEsplenomegaly \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e44 (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e24 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e20 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.257\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eSepsis \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e56 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e29 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e27 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eSeptic shock \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e27 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e17 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e10 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eARDS \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e29 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e15 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e14 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eMultiple organic failure \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e27 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e16 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e11 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 599px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSimultaneous opportunistic and other infections\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eMucocutaneous candidiasis \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e65 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e32 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e33 (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eCoccidioidomycosis \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.389\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eCryptococcosis \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eCryptosporidium disease \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.596\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eHIV encephalopathy \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e4 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.267\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eHistoplasmosis \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e13 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e10 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eKaposi sarcoma \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e21 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e11 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e10 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.419\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003e\u003cem\u003ePneumocystis jirovecii\u0026nbsp;\u003c/em\u003epneumonia \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e49 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e23 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e26 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.644\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eSalmonella disease \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.411\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eHepatitis B virus \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e5 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 262px;\"\u003e\n \u003cp\u003eHepatitis C virus \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e5 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Sociodemographic and clinical characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Chi square test of independence or Fisher\u0026rsquo;s exact test was performed accordingly.\u003c/p\u003e\n\u003cp\u003e**Student\u0026rsquo;s T (with Welch correction according to Levene test for variance equality) or Mann-Whitney U test was performed accordingly.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus, SD: standard deviation, BMI: body mass index, ART: antiretroviral therapy, ARDS: acute respiratory distress syndrome.\u003c/p\u003e\n\u003cp\u003eBiochemical parameters upon admission did not demonstrate significant differences between both groups, except for the total leukocyte count, which was higher in the CMV-negative viremia group (\u003cem\u003ep\u003c/em\u003e = 0.045). The biochemical parameters at admission can be found in Supplementary appendix S2.\u003c/p\u003e\n\u003cp\u003eAt baseline, HIV VL was similar between both groups (\u003cem\u003ep\u003c/em\u003e = 0.982), presenting a median of 70,616 copies/mL (IQR = 262-620,661). Baseline CD4 counts were very similar between groups (\u003cem\u003ep\u003c/em\u003e = 0.895) with a median of 42 cells/\u0026mu;L (IQR = 18-106). At 90-day after admission, HIV viral suppression (\u0026lt;50 copies/mL) was achieved by 72 (37%) of the total sample, 33 (38%) in the CMV positive group vs 39 (36%) in the CMV negative group (\u003cem\u003ep\u003c/em\u003e = 0.709). A total of 108 (55%) presented with a HIV VL lower than 200 copies/ML, 46 (53%) in the CMV group vs 62 (57%) in the CMV negative group (\u003cem\u003ep\u003c/em\u003e = 0.636). CD4 T cell reconstitution was achieved by both groups similarly with 31 (16%) with a CD4 count higher than 200 cells/mL, 15 (17%) in the CMV positive group vs 16 (15%) in the CMV negative group (\u003cem\u003ep\u003c/em\u003e = 0.600). Both groups recovered CD4 similarly at day 90 after admission (\u003cem\u003ep\u003c/em\u003e = 0.821). Immunovirological dynamics at baseline and at 90-day follow-up are shown in Table 2.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Immunovirological dynamics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003eCMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eNo CMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003en = 195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003en = 86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003en = 109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHIV VL \u0026ndash; (copies/mL)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e70,616 (262-620661)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e123,914 (148-622,889)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e51,619 (353-642,412)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.982\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHIV VL log \u0026ndash; (copies/mL) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e4.23 (2.4-5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e5.09 (2.1-5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.71 (2.5-5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eCD4 \u0026ndash; (cells/mL) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e42 (18-106)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e43 (14-118)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e42 (19-91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.895\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eCD4 \u0026ndash; (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e8 (4-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e8 (4-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e8 (4-15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.935\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDay 90\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHIV VL \u0026ndash; (copies/mL) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e65 (40 - 635)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e56 (40 -565)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e75 (40-715)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 200 \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e108 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e46 (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e62 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.636\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt; 50 \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e72 (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e33 (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e39 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.709\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eHIV VL log \u0026ndash; (copies/mL) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e1.96 (1.6-3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e1.89 (1.6-3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e1.96 (1.6-3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.737\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eCD4 \u0026ndash; (cells/mL) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e113 (61-172)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e120 (49-178)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e103 (69-164)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.821\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt; 200 \u0026nbsp;\u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e31 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e15 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e16 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 174px;\"\u003e\n \u003cp\u003eCD4 \u0026ndash; (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e11 (6-17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e10 (5-16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e13 (6-17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Immunovirological dynamics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Student\u0026rsquo;s T (with Welch correction according to Levene test for variance equality) or Mann-Whitney U test was performed accordingly.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus, VL: viral load, CD4: CD4 T lymphocytes, Log: logarithmic.\u003c/p\u003e\n\u003cp\u003eRegarding microbiological isolation, 139 (71%) participants presented disease caused by TM, of which 139 (71%) were identified as \u003cem\u003eM. tuberculosis.\u003c/em\u003e NTM were isolated in 34 (17%) participants, of which 2 (1%) were \u003cem\u003eM. simiae\u003c/em\u003e and 32 (16%) were identified as MAC\u003cem\u003e,\u0026nbsp;\u003c/em\u003ethe rest were not identified or were not isolated microbiologically and therefore were considered as suspected TM or NTM disease. Mycobacterium tuberculosis (MTB) resistance phenotype in this cohort was mostly represented by pan-susceptible MTB in 115 (59%), followed by 10 (5%) extensively resistant MTB, 7 (4%) multidrug resistant MTB, monoresistant MTB (mainly to isoniazid) in 4 (2%) participants, and the remaining study participants did not undergo MTB drug susceptibility testing. Furthermore, diagnosis by GeneXpert was performed and resulted positive in 121 (62%) participants, of which 15 (8%) had rifampicin resistance. GeneXpert confirmation was higher in the no CMV viremia group (56% vs 67%, \u003cem\u003ep\u003c/em\u003e = 0.041). Regarding disease presentation, disseminated disease was the most common, presenting in 108 (55%), followed by extrapulmonary disease presented by 51 (26%) participants and lastly pulmonary disease in 36 (18%) participants. Extrapulmonary affected sites were mainly lymph nodes (18%), followed by central nervous system (11%). Microbiologic characteristics are shown in Table 3.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Microbiological characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eCMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eNo CMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003en = 195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003en = 86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003en = 109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMycobacterial disease confirmation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eMicrobiological confirmation \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e176 (90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e77 (90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e99 (91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Smear \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e67 (34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e25 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e42(39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;MTB Culture \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Pan-susceptible MTB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e115 (59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e53 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e62 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.503\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Monoresistant MTB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e4 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.436\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; MDR MTB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e6 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; XDR MTB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e10 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e7 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.356\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMycobacteria species\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e139 (71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e58 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e81 (74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.364\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u003cem\u003eMycobacterium avium complex\u003c/em\u003e \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e32 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e17 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e15 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u003cem\u003eMycobacterium. simiae\u003c/em\u003e \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e2 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eNot identified \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eNot isolated \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e21 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e11 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e10 (9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGeneXpert confirmation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003ePositive GeneXpert \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e121 (62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e48 (56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e73 (67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eRifampicin resistance \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e15 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e3 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e12 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMycobacterial disease confirmation site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003ePulmonary \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e36 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e9 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e27 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eDisseminated \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e108 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e54 (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e54 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.044\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003eExtrapulmonary \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e51 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e23 (27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e28 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0.498\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Central Nervous System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e21 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e10 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e11 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"8\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Lymphatic ganglia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e35 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e14 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e21 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Gastrointestinal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e8 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e4 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e4 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Renal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Pleural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e11 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e6 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e5 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Pericardic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Bone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Articular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 68px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e1 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Microbiological characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Chi square test of independence or Fisher\u0026rsquo;s exact test was performed accordingly.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus, MTB: \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e, MDR: multi-drug resistant, XDR: extensively resistant.\u003c/p\u003e\n\u003cp\u003eStudy outcomes are delineated in Table 4. Hospital stay duration was similar in both groups (18 vs 17 days, \u003cem\u003ep\u003c/em\u003e = 0.326). Moreover, IRIS presentation and type of IRIS were not different (\u003cem\u003ep\u003c/em\u003e = 0.558) between the study groups. Similarly, no significant differences were observed in culture negativity at 90 days (55% vs 59%, \u003cem\u003ep\u003c/em\u003e = 0.747), mycobacterial treatment failure (24% for both groups, \u003cem\u003ep\u003c/em\u003e = 0.738), or disease relapse (13% vs 4%, \u003cem\u003ep\u003c/em\u003e = 0.060). The overall mortality of the study was 13%, showing no differences between both groups (17% vs 10%, \u003cem\u003ep\u003c/em\u003e = 0.134).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 4. Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"602\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003eCMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003eNo CMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en = 195\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003en = 86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003en = 109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eHospital stay \u0026ndash; days (IQR)**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e17 (11-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e18 (11-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e17 (13-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eIRIS \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e54 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e22 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e32 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.558\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eIRIS type \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unmasked\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e33 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e13 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e20 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 53px;\"\u003e\n \u003cp\u003e0.817\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Paradoxical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e21 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e9 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e12 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eCulture negativization at 90 days \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e111 (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e47 (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e64 (59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eMycobacterial treatment failure \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e47 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e21 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e26 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eRelapse \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e15 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e11 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e4 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 250px;\"\u003e\n \u003cp\u003eDeaths \u0026ndash; no. (%)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e26 (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e15 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e11 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Outcomes.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*Chi square test of independence or Fisher\u0026rsquo;s exact test was performed accordingly.\u003c/p\u003e\n\u003cp\u003e**Student\u0026rsquo;s T (with Levene test for variance equality) or Mann-Whitney U test was performed accordingly.\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus, IQR: interquartile range, IRIS: immune reconstitution inflammatory syndrome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the survival analysis at 90-day follow-up, a total of 195 participants were included, of which 26 died. Divided by groups, we observed that 11 participants without CMV viremia died compared to 15 participants with CMV viremia. The Kaplan-Meier curves and survival tables are presented in Figure 2 and Table 5. In addition, the comparison between groups was carried out with the Log Rank test (Mantel-Cox) without showing significant differences (Chi square = 2.161, \u003cem\u003ep\u003c/em\u003e = 0.142). Furthermore, the hazard ratio of mortality in individuals presenting with active mycobacterial disease co-infected with CMV in relation with the individuals with only mycobacterial disease did not present statistical significance (HR = 1.773, 95% CI: 0.8163-3.852).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Number of patients at risk by day\u003c/strong\u003e\u003c/p\u003e\n\u003ctable class=\"MsoNormalTable\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"9\" valign=\"top\" style=\"width: 433px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003eNumber of patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp class=\"MsoNormal\"\u003eNo CMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp class=\"MsoNormal\"\u003eCMV viremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp class=\"MsoNormal\"\u003eDays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp class=\"MsoNormal\" align=\"center\"\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Outcomes.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: CMV: cytomegalovirus.\u003c/p\u003e\n\u003cp\u003eFinally, the Cox proportional hazard analysis (Table 6) revealed several significant predictors of survival outcomes. Participants with severe sepsis had 3.35 times higher mortality risk (95% CI:1.11-10.11; \u003cem\u003ep\u003c/em\u003e = 0.032), while those with multiple organ failure showed 3.18-fold increased risk (95% CI: 1.24-8.19; \u003cem\u003ep\u003c/em\u003e = 0.016). Higher BMI was observed as a protective factor (HR = 0.84 per unit; 95% CI: 0.72-0.99; \u003cem\u003ep\u003c/em\u003e = 0.042). CD4 count showed borderline significance as a protective factor (HR = 0.99 per cell; 95% CI 0.97-1.00; \u003cem\u003ep\u003c/em\u003e = 0.058). Age, alcohol consumption, multiple opportunistic infections, HIV VL and CMV group status did not show statistically significant associations. The model demonstrated excellent discriminative ability (concordance = 0.869) and overall significance (likelihood ratio test = \u003cem\u003ep\u003c/em\u003e \u0026lt;0.0001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilarly, we conducted a Cox regression analysis of mycobacterial disease relapse risk (Table 6) in which we identified several significant predictors. Immune failure (HR = 6.70; 95% CI: 2.09-21.52; \u003cem\u003ep\u003c/em\u003e = 0.001) was strongly associated with increased relapse risk. Current smokers presented 3.45-fold increased risk (95% CI: 1.02-11.68; \u003cem\u003ep\u003c/em\u003e = 0.046), as did participants in the CMV group (HR = 4.14; 95% CI: 1.22-14.09;\u003cem\u003e\u0026nbsp;p\u003c/em\u003e = 0.023). Hospitalization length showed no significance (HR = 0.97 per day; \u003cem\u003ep\u003c/em\u003e = 0.154), similar to IRIS presentation that showed a non-significant reduction in relapse risk (HR = 0.21; \u003cem\u003ep\u003c/em\u003e = 0.138). Similar to the survival model, this model had excellent discrimination (concordance = 0.863) and overall significance (likelihood ratio test \u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6. Comparative Multivariable Cox Regression Analyses for Mortality and Relapse Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 121px;\"\u003e\n \u003cp\u003ePredictor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 50px;\"\u003e\n \u003cp\u003eLevel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 213px;\"\u003e\n \u003cp\u003eMortality Analysis\u003c/p\u003e\n \u003cp\u003e(N = 195, Events = 26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 206px;\"\u003e\n \u003cp\u003eRelapse Analysis\u003c/p\u003e\n \u003cp\u003e(N = 183, Events = 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003eaHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eaHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic Factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 468px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eper year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e1.02 (0.99-1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eper unit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.84 (0.72-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.042\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical Factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 468px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eSmoking status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e3.45 (1.02-11.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.046\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eHospital days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eper day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e0.97 (0.93-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.154\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eSevere sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e3.35 (1.11-10.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.032\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eMultiple organ failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e3.18 (1.24-8.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eIRIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e0.21 (0.03-1.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eImmune failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e6.70 (2.09-21.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eMultiple OI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e1.70 (0.62-4.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHIV-Related Factors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 468px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eHIV viral load (log)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eper log\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e1.02 (0.80-1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eCD4 count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eper cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e0.99 (0.97-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.058*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eCMV group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 50px;\"\u003e\n \u003cp\u003eCMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 145px;\"\u003e\n \u003cp\u003e1.29 (0.56-2.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e4.14 (1.22-14.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6. Comparative Multivariable Cox Regression Analyses for Mortality and Relapse Outcomes.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModel Fit Statistics: Mortality: Concordance = 0.869, LR test p \u0026lt;0.0001, Relapse: Concordance = 0.863, LR test p \u0026lt;0.0001. Abbreviations: aHR: adjusted Hazard Ratio; CI: Confidence Interval, OI: Opportunistic infections; IRIS: Immune Reconstitution Inflammatory Syndrome, CMV: Cytomegalovirus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*Borderline significance (p\u0026lt;0.1).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the baseline characteristics of both groups demonstrated significant similarities, ensuring a homogeneous and comparable sample. Immunovirological dynamics were comparable between the groups, with no statistically significant differences observed in HIV viral suppression at the 90-day follow-up, as assessed using thresholds of \u0026lt;200 and \u0026lt;50 copies/mL.\u0026nbsp;These results are a reflection of the profound baseline immunosuppression and high HIV VL at admission. Most individuals presented with advanced HIV, which is an imperative factor known to delay virological response. Similarly, CD4 cell counts did not differ significantly between the groups by day 90 post-admission. These findings suggest that CMV viremia occurring alongside active mycobacterial infection is not associated with delayed HIV viral suppression or impaired immune recovery. This aligns with existing evidence indicating that individuals with opportunistic infections and advanced immunosuppression often exhibit prolonged delays in achieving viral suppression and immune reconstitution (20).\u003c/p\u003e\n\u003cp\u003eOverall mortality in this study (13%) was consistent with the one reported by the WHO in the Global Tuberculosis Report 2024 (12%) (1).\u0026nbsp;While this cohort did not demonstrate CMV co-infection as an independent prognostic marker for mortality in PLWH and active mycobacterial disease, our analysis revealed CMV viremia as a significant predictor of mycobacterial disease relapse. This may reflect our center’s standardized protocol of rapid CMV PCR testing and end-organ disease identification, and preemptive antiviral initiation, which likely mitigated systemic CMV effects while insufficiently preventing its localized immunomodulatory impact on mycobacterial control. This observation aligns with the known immunomodulatory effects of CMV in advanced immunosuppression. Mycobacterial control fundamentally requires a robust Th1 response (mediated by IFN-γ, TNF-α, and IL-12) (21). However, during CMV coinfection, persistent interferon-alpha (IFN-α) production by plasmacytoid dendritic cells disrupts Th1 polarization through IL-12 signaling suppression (22). Concurrently, CMV drives clonal expansion of terminally differentiated CD8 T cells, depleting resources for mycobacteria-specific Th1 responses (23). All together, these mechanisms impair macrophage activation and granuloma integrity, creating a permissive environment for mycobacterial dissemination and worse clinical outcomes, even in the absence of overt CMV end-organ disease, which can be seen in the differences in the presentation of the mycobacterial disease between groups (24). Furthermore, CMV reactivation is associated with an increased mortality among PLWH with severe immunodeficiency. This has been demonstrated throughout several clinical settings which found that CMV viremia predicts higher mortality risk even with prompt ART initiation (25). Notably, in our cohort (where ART initiation occurred without delays) this association persisted, suggesting CMV’s pathogenic role is an important factor beyond delays in ART.\u003c/p\u003e\n\u003cp\u003eRegarding clinical manifestations, interestingly, the CMV-positive group exhibited significantly lower rates of fever compared to the CMV-negative group. While this can be counterintuitive, this finding is supported by the emerging evidence on how inflammatory responses are blunted in people with advanced immunosuppression driven by CD4 depletion which can impair pyrogenic cytokine production, CMV-encoded immunomodulators like UL83 which can directly suppress IL-1β and IL-6, and CMV-driven IL-10 overexpression which systemically attenuate febrile responses (26). This paradoxical absence of fever underscores the importance of considering CMV coinfection even in afebrile people with advanced HIV. Moreover, the low frequency of dyspnea among the CMV-infected group prompted further investigation to evaluate if this represented a true biological effect or confounding by mycobacterial disease localization. We conducted a focused subanalysis of participants with pulmonary mycobacterial disease, in which dyspnea prevalence was no longer significant (\u003cem\u003ep\u003c/em\u003e = 0.557, Supplementary Appendix S3) suggesting that the initial observation may have reflected differential distribution of extrapulmonary involvement rather than a direct CMV-mediated effect on respiratory symptoms. This highlights the importance of accounting for disease localization when evaluating clinical manifestations in immunocompromised hosts with multiple concurrent infections.\u003c/p\u003e\n\u003cp\u003eGeneXpert diagnostic performance for mycobacterial disease varies depending on the level of immunosuppression, clinical presentation, and bacillary load (27). In our cohort, the CMV-negative group showed a higher incidence of pulmonary mycobacterial disease, which may explain their increased GeneXpert positivity rates, as pulmonary forms typically have higher bacillary loads. Conversely, the CMV-positive group demonstrated greater prevalence of disseminated disease and potentially more paucibacillary presentation, which are features associated with reduced GeneXpert sensitivity and specificity that may reflect their advanced immunosuppression. This pattern suggests profound T-cell dysfunction facilitating mycobacterial dissemination, and CMV-mediated endothelial damage potentially enhancing systemic spread (28). Together, these factors may create a diagnostic paradox where people with greatest mycobacterial disease burden have lower GeneXpert positivity due to bacillary dissemination and pauci-bacillary presentations.\u003c/p\u003e\n\u003cp\u003eOur findings reveal different risk profiles for mortality and relapse that highlight the critical role of organ dysfunction in mortality (sepsis and multiple organ dysfunction) and immune dysregulation in disease relapse (immune failure). The protective effect of higher BMI against mortality aligns with the obesity paradox observed in some other chronic\u0026nbsp;diseases (29). Clinically, these results advocate for 1) aggressive sepsis management in high-risk people, particularly those with low BMI, 2) enhanced monitoring for CMV-positive individuals or those with immune failure, and 3) careful documentation to distinguish relapse events to prevent complications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is limited by its own design as it is retrospective in nature\u0026nbsp;which introduces potential unmeasured confounders. Some of the key data limitations include the lack of CMV seroprevalence data (which prevents assessment of CMV reactivation or new infection), absence of detailed documentation regarding sample types used for GeneXpert testing, and missing longitudinal measurements such as serial CMV serology, VL monitoring, and mycobacterial therapy adherence, which are critical variables for assessing viremia persistence, end-organ disease progression, and treatment efficacy over time. Additionally, the small event numbers may limit statistical power.\u003c/p\u003e\n\u003cp\u003eHowever, the study demonstrates robust model discrimination supporting its clinical utility. Importantly, it provides the first investigation into the relationship between active mycobacterial co-infection and CMV in PLWH within the Mexican population, which is important as it addresses a key knowledge gap.\u003c/p\u003e\n\u003cp\u003eFuture research should prioritize prospective designs to properly control for confounding variables and incorporate CMV-specific immune pathway analysis. The development of dual-outcome prediction models could further refine personalized monitoring strategies. These results highlight the need for distinct clinical approaches to mortality prevention versus relapse mitigation in this high-risk group.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study, as far as we know, represents the first investigation of CMV and mycobacterial co-infection dynamics in PLWH from the Mexican population. While our analysis did not demonstrate statistically significant differences in mortality or secondary outcomes (including IRIS presentation, treatment failure or disease relapse, between individuals with and without CMV co-infection, several important considerations emerge from our findings.\u003c/p\u003e\n\u003cp\u003eThe lack of observed association may reflect the effectiveness of current standard-of-care practices in our clinical setting, particularly regarding immune reconstitution and opportunistic infection management. However, important study limitations must be acknowledged as discussed earlier.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNotwithstanding these limitations, our results demonstrate robust model discrimination that supports the clinical relevance of our analytical approach. The findings suggest that in resource-appropriate settings with adequate ART and mycobacterial therapy coverage, CMV co-infection may not independently worsen outcomes in this population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTM: Tuberculous mycobacterial.\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization.\u003c/p\u003e\n\u003cp\u003eHIV: Human Immunodeficiency Virus.\u003c/p\u003e\n\u003cp\u003eNTM: Non-tuberculous mycobacteria.\u003c/p\u003e\n\u003cp\u003ePLWH: People living with human immunodeficiency virus.\u003c/p\u003e\n\u003cp\u003eCD4: CD4+ T lymphocytes.\u003c/p\u003e\n\u003cp\u003eART: Antiretroviral therapy.\u003c/p\u003e\n\u003cp\u003eAIDS: Acquired immunodeficiency syndrome.\u003c/p\u003e\n\u003cp\u003eMAC: Mycobacterium avium-intracellulare complex.\u003c/p\u003e\n\u003cp\u003eCMV: Cytomegalovirus.\u003c/p\u003e\n\u003cp\u003eELISA: Enzyme-linked immunosorbent assay.\u003c/p\u003e\n\u003cp\u003eINER: Instituto Nacional de Enfermedades Respiratorias.\u003c/p\u003e\n\u003cp\u003eVL: Viral load.\u003c/p\u003e\n\u003cp\u003ePCP: Pneumocystis jirovecii pneumonia.\u003c/p\u003e\n\u003cp\u003eIRIS: Immune reconstitution inflammatory syndrome.\u003c/p\u003e\n\u003cp\u003eAIC: Akaike’s Information Criterion.\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index.\u003c/p\u003e\n\u003cp\u003eARDS: Acute respiratory distress syndrome.\u003c/p\u003e\n\u003cp\u003eMTB: Mycobacterium tuberculosis.\u003c/p\u003e\n\u003cp\u003eMDR: Multi-drug resistant.\u003c/p\u003e\n\u003cp\u003eXDR: Extensively resistant.\u003c/p\u003e\n\u003cp\u003eHR: Hazard ratio.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval.\u003c/p\u003e\n\u003cp\u003eOI: opportunistic infection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eEthics approval and consent to participate:\u003c/u\u003e The research and ethics committee of the Instituto Nacional de Enfermedades Respiratorias \u0026quot;Ismael Cos\u0026iacute;o Villegas\u0026quot; reviewed and approved the preparation and development of this retrospective study with acceptance number C34-22, as it adhered to the national regulations (\u0026ldquo;Ley General de Salud en Materia de Investigaci\u0026oacute;n\u0026rdquo; and the NOM-012-SSA3-2012, which establishes the criteria for the execution of research projects for health in human beings) and the international regulations (Declaration of Helsinki, according to its last assembly in Fortaleza, Brazil 2013). Likewise, a waiver of informed consent was approved by both research and ethics committee.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eClinical Trial:\u003c/u\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication:\u003c/u\u003e The study did not present any individual-level identifiable data (including medical images, personal details, or multimedia records) requiring specific consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of data and materials:\u003c/u\u003e All data generated and analyzed during the present study were included in the file titled \u0026ldquo;Supplementary_Raw Data\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting of interests:\u003c/u\u003e All authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003ctable border=\"1\" width=\"545\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eXavier A. Flores-Andrade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAmy B. Peralta-Prado\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEduardo Porras-Rosales\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAndrea C\u0026aacute;rdenas-Ortega\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eV\u0026iacute;ctor H. Ahumada-Topete\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSantiago \u0026Aacute;vila-R\u0026iacute;os\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cu\u003eFunding:\u003c/u\u003e This work was supported by funds from the Mexican Government (Programa Presupuestal P016; Anexo 13 del Decreto del Presupuesto de Egresos de la Federaci\u0026oacute;n). The funders had no role in the study design, data collection and analysis, publication decisions, or manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthor contributions and information:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003e1. Corresponding author: XAFA, MD: Author and responsible for: Conceptualization, data curation, formal analysis, investigation, methodology, visualization, writing, review, and editing of the original manuscript. Mail:\u0026nbsp;[email protected] ORCID: 0000-0003-1529-7276. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias \u0026ldquo;Ismael Cos\u0026iacute;o Villegas\u0026rdquo; (INER), Mexico City, Mexico.\u003c/p\u003e\n\u003cp\u003e2. ABPP, MD, MSc: Author and responsible for: Data curation, formal analysis, methodology, project administration, supervision, review and editing of the original draft.\u003c/p\u003e\n\u003cp\u003eMail:\u0026nbsp;[email protected], ORCID: 0000-0002-6379-9134. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias \u0026ldquo;Ismael Cos\u0026iacute;o Villegas\u0026rdquo; (INER), Mexico City, Mexico.\u003c/p\u003e\n\u003cp\u003e3. EPR, MD: Author and responsible for: Conceptualization, data curation, investigation, methodology. Mail:\u0026nbsp;[email protected], OCRID: 0000-0003-2589-8497. Hospital \u0026ldquo;Manolo Morales\u0026rdquo;, Managua, Nicaragua.\u003c/p\u003e\n\u003cp\u003e4. ACO, MD: Author and responsible for: Conceptualization, data curation, investigation, methodology. Mail:\u0026nbsp;[email protected], ORCID: 0009-0000-1827-3283. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias \u0026ldquo;Ismael Cos\u0026iacute;o Villegas\u0026rdquo; (INER), Mexico City, Mexico.\u003c/p\u003e\n\u003cp\u003e5. VHAT, MD: Responsible for: Project administration, supervision, review and editing of the original manuscript. Mail:\u0026nbsp;[email protected], ORCID: 0000-0001-9822-3496.\u003c/p\u003e\n\u003cp\u003eInstituto Nacional de Enfermedades Respiratorias \u0026ldquo;Ismael Cos\u0026iacute;o Villegas\u0026rdquo; (INER), Mexico City, Mexico.\u003c/p\u003e\n\u003cp\u003e6. Santiago \u0026Aacute;vila-Rios, PhD: Responsible for: Funding acquisition, project administration, resources, supervision, review and editing of the original draft. Mail:\u0026nbsp;[email protected], ORCID: 0000-0003-3371-4248. Centre for Research in Infectious Diseases (CIENI), Instituto Nacional de Enfermedades Respiratorias \u0026ldquo;Ismael Cos\u0026iacute;o Villegas\u0026rdquo; (INER), Mexico City, Mexico.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgements:\u003c/u\u003e None.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAI-Assisted Editing Statement:\u003c/u\u003e During the preparation of this manuscript, the authors used DeepSeek AI (DeepSeek Chat, version 3) for grammar correction, sentence clarity improvement, and language polishing. The final content was reviewed and approved by all authors, who take full responsibility for the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal Tuberculosis Report. 2023 [Internet]. [cited 2024 May 7]. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://smw.ch/index.php/smw/article/view/2123/3125\u003c/span\u003e\u003cspan address=\"https://smw.ch/index.php/smw/article/view/2123/3125\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cytomegalovirus, Mycobacterium, HIV, AIDS","lastPublishedDoi":"10.21203/rs.3.rs-6405843/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6405843/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003eBackground:\u003c/u\u003e The mycobacterial and cytomegalovirus co-infection represents a critical intersection of infectious challenges, especially in the context of people living with human immunodeficiency virus infection. This relation raises questions on whether this co-infection represents increased mortality risk. Elucidating the critical interplay between these two microorganisms is imperative to promptly assess and intervene in the patient’s clinical evolution. The primary endpoint of the present study was to compare the 90-day mortality of immunocompromised people living with HIV/AIDS co-infected with tuberculous and non-tuberculous mycobacteria with and without cytomegalovirus infection.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eMethods:\u003c/u\u003e We conducted a comparative, observational, retrospective study in a tertiary care setting in Mexico City that provides clinical care for people living with HIV. Sociodemographic, clinical, and biochemical data was collected to assess disease evolution, as well as a 90-day retrospective follow-up to evaluate mortality. Statistical analysis was performed to evaluate sample heterogeneity. A survival analysis and Cox proportional hazards analysis were performed to specifically elucidate the effect on mortality of people who presented co-infection of active mycobacterial disease with or without Cytomegalovirus.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eResults:\u003c/u\u003e Mortality between groups failed to demonstrate statistical significance (HR: 1.773, 95%CI: 0.8163, 3.852; \u003cem\u003ep\u003c/em\u003e = 0.1479). Aside from the survival analysis, overall mortality at 90-day follow-up was 13%, which is similar to worldwide mortality reported by the World Health Organization (12%). Severe sepsis (\u003cem\u003ep\u003c/em\u003e = 0.032) and multiple organ failure (\u003cem\u003ep\u003c/em\u003e= 0.016) predicted mortality, while immune failure (\u003cem\u003ep\u003c/em\u003e = 0.001) and a positive cytomegalovirus viremia (\u003cem\u003ep\u003c/em\u003e= 0.023) increased risk for disease relapse. Higher body mass index was protective against mortality (\u003cem\u003ep\u003c/em\u003e = 0.042).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusions:\u003c/u\u003eThis study of cytomegalovirus and mycobacterial co-infections in Mexican people living with HIV found no significant mortality or outcome differences by cytomegalovirus viremic status, potentially reflecting effective standard of care. While limited by sample size, the robust model discrimination suggests Cytomegalovirus co-infection may not independently worsen outcomes in well-managed populations. These findings highlight the importance of maintaining optimal antiretroviral therapy and mycobacterial treatment coverage in resource-appropriate settings.\u003c/p\u003e","manuscriptTitle":"Clinical outcome of HIV/AIDS patients with Mycobacterium spp. disease associated with Cytomegalovirus viremia: a retrospective study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 03:13:02","doi":"10.21203/rs.3.rs-6405843/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e21a17d-8e71-4f76-84f8-0d2cc3797533","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T11:53:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-07 03:13:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6405843","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6405843","identity":"rs-6405843","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}