Incidence of osteoporosis and osteopenia in men with HIV+ and a history of Kaposi sarcoma

Incidence of osteoporosis and osteopenia in men with HIV+ and a history of Kaposi sarcoma | 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 Incidence of osteoporosis and osteopenia in men with HIV+ and a history of Kaposi sarcoma Patricia Cornejo-Juárez This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1626275/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background: Low bone mineral density (BMD) is a common complication of chronic HIV infection, reported between 30%-67% for osteopenia, and between 15%-30% for osteoporosis. Kaposi Sarcoma (KS) is an angioproliferative disease, mediated by cytokines which contributes to inflammation. The objective was to assess the prevalence of BMD in a cohort of HIV+ men with a history of KS. Methods: A retrospective study was performed from January 2019 to March 2021, in men over the age of 40 years and/or with more than 3 years of antiretroviral drugs. Odds Ratios with 95% Confidence Intervals were calculated. P values of ≤0.05 were considered statistically significant. Results: Eighty-four patients were included; mean age was 45.9 ± 8.8 years, and mean time from HIV diagnosis was 9.7 ± 6.8 years. The median baseline CD4+ was 102 cells (IQR 40, 216), and the median viral load was 143 582 copies/ml (IQR 26 527, 341 500). At the time of Dual X-ray Absorptiometry, the median CD4+ count was 361 cell/mL (IQR 225, 518) and the HIV-viral load was undetectable in 80 patients (95.2%). Osteoporosis was documented in 23.8% and osteopenia in 53.6%. The analysis comparing main risk factors, including different ARV drugs for low BMD did not show statistical differences. In the multivariate analysis, NNTRI and disseminated KS were found as protective factors for low BMD. Conclusions: The low BMD reported in this cohort may be related to several risk factors, it is advisable to establish preventive measures for BMD loss, regardless of age. Osteoporosis Osteopenia HIV Kaposi sarcoma Antiretroviral therapy Bone Mineral Density (BMD). Introduction Osteoporosis is characterized by low Bone Mineral Density (BMD) and the microarchitectural deterioration of bone tissue, with an increase in bone fragility and risk of pathological fractures. It is currently considered the most common metabolic disease, causing morbidity and disability [ 1 , 2 ]. BMD decreases after the age of 30 years in both women and men, with a much more rapid rate of bone loss in women during perimenopause and early menopause; the risk can vary up to 10-fold depending on the country-of-origin, and other risk factors include vitamin D deficiency, smoking, high alcohol consumption, corticosteroid therapy, lifestyle, weight loss, chronic inflammation, hypogonadism, and HIV chronic infection [ 3 ]. Over the past 25 years, there has been an increase in the life expectancy in HIV population with access to combined Antiretroviral Therapy (cART), which has led to an increase in chronic degenerative diseases to a higher extent than in general population [ 4 ]. BMD loss is a common complication of chronic HIV infection and its therapy [ 2 , 5 ]. Rates have been reported of between 30 and 67% for osteopenia and of between 15 and 30% for osteoporosis, corresponding to an Odds Ratio (OR) of 6.4 for osteopenia and of 3.7 for osteoporosis when compared with HIV-uninfected individuals [ 2 , 6 , 7 ]. There are reports that showed a higher incidence in patients receiving Tenofovir Disoproxil Fumarate (TDF) or Protease Inhibitors (PI) containing cART regimes [ 6 , 8 ]. Kaposi Sarcoma (KS) is an angioproliferative disease caused by Human Herpes Virus-8 (HHV-8); this virus possesses genes that mimic human oncogenes and codify for the inflammation, proliferation, and differentiation of spindle cells. HHV-8 conditions high levels of circulating cytokines, which are related with chronic inflammation, a recognized factor for BMD loss [ 9 ]. The prevalence of low BMD has not been studied in HIV-infected patients with a history of KS. The aim of the study was to evaluate the prevalence of osteopenia and osteoporosis in a cohort of HIV-positive men with a history of KS. Methods A retrospective study was performed from January 2019 to March 2021, in HIV-positive men with a history of KS who were followed at the HIV/AIDS Cancer Clinic of the Instituto Nacional de Cancerología in Mexico City, Mexico. The HIV/Cancer Clinic was founded in 1990; since then, 1,365 patients have been treated. During the study period, there were 480 patients who were attended distributed as 384 (80%) men and 96 (20%) women. The main neoplasm in HIV-men at our institution is KS, with a mean of 55 new cases per year during the last 5-year period, mainly in men who have sex with men (MSM). We included all HIV-infected men older than 30 years who had received at least 3 years of cART, with a diagnosis of KS, who had a Dual X-ray Absorptiometry (DXA) performed within the last 12 months. The size of the sample was determined by convenience. Exclusion criteria were patients who had received drugs that can alter BMD (such as Prednisone, bisphosphonates, and calcium), those who had received pelvic radiotherapy, had a hip prosthesis, or if data were incomplete in the clinical chart. Informed consent for patients was waived because the study was retrospective, DXA is part of the studies requested for follow-up, and confidentially is preserved for all patients. The study was approved by the Ethics Committee (REF/INCAN/CI/0481/2021). Demographic and clinical data were recorded from clinical charts, included age, date of HIV diagnosis, date of cART initiation, type of cART (classified as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), PI, TDF, and Integrase Strand Transfer Inhibitors [INSTI]), baseline CD4 + lymphocyte count and viral load, last CD4 + and viral load performed prior to the DXA study, date of KS diagnosis, and extension of KS (cutaneous, gastrointestinal, lung, lymph nodes, and lymphedema) were documented and classified as localized or disseminated KS. Disseminated KS was defined as the presence of KS pulmonary disease and/or ≥ 30 KS skin lesions, with or without lymphedema, and/or lymph-node involvement, and/or gastrointestinal tract (GIT) KS involvement. The use, type, and number of chemotherapy cycles were recorded. Risk factors for osteoporosis included smoking habits, alcohol use, drug abuse, Body Mass Index (BMI), physical activity documented in Metabolic Equivalents (METS), and history of fractures. Physical activity was classified as follows: inactive- no activity; low- light or moderate activity < 150 min per week; medium- moderate or vigorous activity 150 to 300 min per week, and as high- vigorous activity, more than 300 min per week [ 10 ]. BMD was measured by DXA (Hologic X-ray Bone Densitometer Discovery™ QDR™ (Hologic, Inc., Waltham, MA, USA). APEX ver. 4.5.3 software programmed for Hispanic race was used. Quantitative measurement of bone mass referring to the amount of mineral matter (calcium) in grams per square centimeter (gr/cm 2 ) was conducted at lumbar spine (L1-L4) and both femoral necks. According to the World Health Organization (WHO), BMD was expressed in relation to a mean reference for young adult female Caucasians (T-score) and grouped accordingly as either normal, osteopenia, or osteoporosis. WHO-established criteria were employed as follows [ 11 ]: Osteoporosis: BMD ≥ 2.5 Standard Deviations (SD) of the T-score. Osteopenia: An intermediate category of bone loss defined as a T-score between − 1 and − 2.5 SD. Normal BMD: T-score between 1.0 and − 0.9 SD at all three sites. The Z-score was used in patients younger than 50 years of age. Statistical analysis The student t test or the Chi 2 test was utilized to compare means for continuous and categorical variables, respectively, among the groups. Variables with a p value of < 0.2 were included in the multivariate logistic regression analysis. Exposure to different ART drugs was analyzed in study participants who received ≥ 3 years of the same drugs. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated. P values of ≤ 0.05 were considered statistically significant. Data were analyzed employing STATA (ver. 14) statistical software. Results During the study period, 123 men with HIV and KS were seen at the HIV/AIDS Clinic. Among these, 105 had received cART for at least 3 years or were older than 30 years of age. There were 17 patients who did not have a DXA performed, and four were lost to follow-up. Eighty-four patients were included; mean age was 45.9 ± 8.8 years, and 53 patients (63.1%) were younger than 50 years of age. Seventeen patients (20.2%) had a documented BMI of 10% of weight prior to HIV diagnosis. Other clinical data are presented in Table 1 . Table 1 Baseline demographic and clinical characteristics in 84 HIV-infected patients with Kaposi sarcoma Characteristic N (%) Age (years) (mean ± S.D.) a 45.9 ± 8.8 Age (years) 50 22 (26.2) 35 (41.7) 22 (26.2) 5 (5.9) BMI b <19 (kg/m 2 ) at HIV diagnosis 17 (20.2) ≥ 10% of weight loss at HIV diagnosis 28 (33.3) Diabetes mellitus 6 (7.1) High blood pressure 14 (16.7) Low or mild physical activity 67 (79.8) Alcohol 46 (54.8) Smoking (history or current) .42 (50) Use of recreational drugs 23 (27.4) Previous fractures 1 (1.2) HIV diagnosis (years) a 9.7 ± 6.8 Basal CD4 + cell/mL (median, IQR) 102 (40, 216) Baseline CD4 + cell/mL c 300 40 (49.4) 18 (22.2) 14 (17.3) 9 (11.1) Baseline HIV-viral load copies/mL d 143 582 (26 527, 341 500) Last CD4 + cell/mL d 361 (225, 518) Last CD4 cell/mL 300 4 (4.7) 13 (15.5) 14 (16.7) 53 (63.1) Undetectable current viral load 80 (95.2) TDF ≥ 3 years e 56 (66.8) TDF (years) a 5.9 ± 4.6 PI ≥ 3 years f 23 (27.4) PI (years) a 6.4 ± 5.2 NNRTI ≥ 3 years g 38 (45.2) NNRTI (years) a 5 ± 4.3 INSTI ≥ 3 years h 16 (19) INSTI (years) a 2.4 ± 1.9 Time from Kaposi sarcoma diagnosis (years) a 8.1 ± 5.8 Kaposi sarcoma involvement Skin ≥ 30 lesions Lymph nodes or lymphedema Mouth mucosal involvement Gastrointestinal tract Lung 41 (48.8) 13 (15.5) 27 (32.1) 45 (53.6) 5 (5.9) Disseminated Kaposi sarcoma 38 (45.2) Chemotherapy Bleomycin/Vincristine Liposomal Doxorubicin 36 (42.8) 35 (97.2) 1 (2.8) Median number of chemotherapy cycles d 3 (2, 6) a S.D: Standard Deviation; b BMI: Body Mass Index; c Data were available for 81 patients; d Median (Interquartile range); e TDF: Tenofovir Disoproxil Fumarate; f PI: Protease Inhibitors; g NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitors; h INSTI: Integrase Strand Transfer Inhibitor. Regarding HIV-related risk factors, mean time from HIV diagnosis was 9.7 ± 6.8 years. Median CD4 + lymphocyte count at baseline was 102 cells/mL (IQR 40, 216), and median viral load was 143 582 copies/mL (IQR 26 527, 341 500). At the time of DXO, the median CD4 + count was 361 cell/mL (IQR 225, 518); 80 (95.2%) patients had an undetectable HIV viral load, the remaining four patients had 116, 138, 976, and 1,014 copies/mL, all related with poor cART adherence. Regarding cART, all patients received NRTI as backbone. Considering those patients who received treatment for ≥3 years, 56 patients (66.8%) had TDF, 23 (27.4%) PI, 38 (45.2%) NNRTI, and 16 (19%), INSTI. Further clinical data are shown in Table 1 . KS was diagnosed with a mean time of 8.1 ± 5.8 years; in 38 patients (45.2%), KS was classified as disseminated. Thirty-six (42.8%) patients received chemotherapy, median cycles were three (IQR 2–6), and all received Bleomycin and Vincristine except for one patient, who received two cycles of liposomal Doxorubicin). According to DXA femoral-neck measurements, eight patients (9.5%) had osteoporosis, 35 (41.7%) osteopenia, and 41 (48.8%) had a normal BMD. In lumbar-spine measurements, 20 (23.8%) had osteoporosis, 45 (53.6%) osteopenia, and 19 (22.6%) had normal BMD. A major decrease was observed in lumbar spine ( p = 0.0007). There were more patients with normal measurements (both in femoral and in spine). Data are depicted in Table 2 . Table 2 Male HIV-infected patients with Kaposi sarcoma who received ≥ 3 years of different antiretrovirals drugs, according to the DXA result Measurement site DXA result NNRTI a ( n = 38, 45.2%) Non-NNRTI a ( n = 46, 54.8) P PI b ( n = 23, 27.4%) Non-PI b ( n = 61, 72.6%) P TDF c ( n = 56, 66.7%) Non-TDF c (28, 33.3%) P INSTI d ( n = 16, 19%) Non-INSTI d ( n = 68, 81%) P Femoral neck Normal ( n = 41, 48.8%) 22 (57.9) 19 (41.3) 0.226 10 (43.5) 31 (50.8) 0.218 27 (48.2) 14 (50) 0.483 8 (50) 33 (48.5) 0.127 Osteopenia ( n = 35, 41.7%) 12 (31.6) 23 (50) 11 (47.8) 24 (39.4) 25 (44.6) 10 (35.7) 7 (43.75) 28 (41.2) Osteoporosis ( n = 8, 9.5%) 4 (10.5) 4 (8.7) 2 (8.7) 6 (9.8) 4 (7.1) 4 (14.3) 1 (6.25) 7 (10.3) Spine Normal ( n = 19, 22.6%) 12 (31.6) 7 (15.2) 0.01 3 (13.05) 13 (24.5) 0.07 12 (21.4) 7 (25) 0.66 3 (18.75) 16 (23.5) 0.727 Osteopenia ( n = 45, 53.6%) 14 (36.8) 31 (67.4) 17 (73.9) 25 (47.1) 29 (51.8) 16 (57.1) 10 (62.5) 35 (51.5) Osteoporosis ( n = 20, 23.8%) 12 (31.6) 8 (17.4) 3 (13.05) 15 (28.3) 15 (26.8) 5 (17.9) 3 (18.75) 17 (25) . a NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitors; b PI: Protease Inhibitors; c TDF: Tenofovir Disoproxil Fumarate; d INSTI: Integrase Strand Transfer Inhibitor. Main risk factors for low BMD, including type and time of the different ARV drugs, were analyzed comparing normal vs. osteoporosis and osteopenia. NNRTI were associated with less BMD loss. In the multivariate analysis, having received NNRTI (OR 0.259, p = 0.04) and having disseminated KS (OR 0.12, p = 0.004) were found as protective factors for osteoporosis and osteopenia. Table 3 demonstrates the univariate and multivariate analyses. Table 3 Univariate and multivariate analysis for osteoporosis and osteopenia in 84 HIV + patients with Kaposi sarcoma. Characteristics Normal DXA ( n = 19, 22.6%) Osteoporosis/Osteopenia ( n = 65, 77.4%) P OR P Age 30 to < 50 years Age ≥ 50 years 14 (73.7) 5 (26.3) 39 (60) 26 (40) 0.418 - - < 10% weight loss at HIV diagnosis ≥ 10% of weight loss 12 (63.2) 7 (36.8) 44 (67.7) 21 (32.3) 0.784 - - Moderate or strong physical activity Low or mild physical activity 1 (5.3) 18 (94.7) 16 (24.6) 49 (75.4) 0.102 1 0.159 (0.01–1.6) 0.115 Never smoked Current or history of smoking 9 (47.4) 10 (52.6) 33 (50.8) 32 (49.2) 1 - - Baseline CD4 count > 100 ab Baseline CD4 count ≤ 100 12 (70.6) 5 (26.4) 28 (44.4) 35 (55.6) 0.05 1 2.18 (0.52–9.11) 0.284 Baseline HIV viral load 100,000 7 (50) 7 (50) 18 (34.6) 34 (65.4) 0.357 - - Last CD4 count > 200 b Last CD4 count < 200 15 (78.9) 4 (21.1) 51 (78.5) 14 (21.5) 1 - - Non-TDF or TDF < 3 years e TDF ≥ 3 years 7 (36.8) 12 (63.2) 21 (32.3) 44 (67.7) 0.784 - - Non-PI or PI < 3 years f PI ≥ 3 years 16 (84.2) 3 (15.8) 45 (69.2) 20 (30.8) 0.251 - - Non-NNRTI or NNRTI < 3 years g NNRTI ≥ 3 years 7 (36.8) 12 (63.2) 39 (60) 26 (40) 0.114 1 0.259 (0.07–0.97) 0.046 Non-INSTI or INSTI < 3 years h INSTI ≥ 3 years 16 (84.2) 3 (15.8) 52 (80) 13 (20) 1 - - Localized Kaposi sarcoma Disseminated Kaposi sarcoma 4 (21.1) 15 (78.9) 42 (64.6) 23 (35.4) 0.001 1 0.12 (0.03–0.51) 0.004 Non-comorbidities Comorbidities 5 (26.3) 14 (73.7) 34 (52.3) 31 (47.7) 0.06 1 0.422 (0.1–1.69) 0.224 a Four patients did not have baseline CD4 in their clinical chart; b cells/mL; c Eighteen patients did not have viral load; d Copies/mL; e TDF: Tenofovir Disoproxil Fumarate; f PI: Protease Inhibitors; NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitors; h INSTI: Integrase Strand Transfer Inhibitor. Discussion Many studies have investigated the prevalence of osteoporosis and osteopenia in HIV-positive patients. However, this is to our knowledge, the first study performed in a cohort of 84 MSM with a history of KS who received cART for more than 3 years and with an age of ≥ 30 years (67.8% were younger than 50 years of age). This study found a rate of osteopenia (53.6%) and osteoporosis (23.8%), similar to those in previous reports carried out in patients with HIV infection, but considerably higher than those reported in male population without HIV. In a study carried out between 2000 and 2009, that included 73% males, 49.6% was reported of osteopenia and 21.7% of osteoporosis [ 12 ]. Another study conducted in 2017, which included 108 patients with HIV (79 were males), it was reported that 23% of those studied had low BMD [ 13 ]. The current guidelines do not recommend the measurement of BMD in HIV-infected patients younger than 50 years of age [ 14 – 16 ]. We included patients who have been receiving ARV treatment for at least 3 years, and although there were no differences between younger (< 50 years, n = 53) and older (≥ 50 years, n = 31) patients, osteopenia and osteoporosis were considerably high in young patients (39/53, 73.6%). BMD loss may be the result of complex interactions between HIV infection and/or long-term cART and patient lifestyle-related factors [ 17 ]. The risk factors for osteoporosis are classified as unmodifiable, modifiable, and secondary causes. Unmodifiable risk factors include older age, feminine gender, family history of osteoporosis, and history of previous fractures. Modifiable risk factors include low BMI, tobacco use, poor physical activity, use of long-term glucocorticoid treatment, long-term anticonvulsant therapy, excessive use of alcohol, and a low dietary intake of vitamin D or calcium. Secondary causes include type 1 diabetes, rheumatoid arthritis, anorexia nervosa, hyperthyroidism, hyperparathyroidism, hypogonadism or premature menopause, chronic malnutrition or malabsorption, and chronic liver disease [ 2 ]. In general population, osteoporosis in men is predominantly in cortical-bone tissue (hip area), while for HIV + patients, osteoporosis preferably affects trabecular bone, especially involving the lumbar spine [ 17 ]. In our study, a lower BMD was found predominantly in lumbar spine (77.4%) compared with femoral neck (51.2%). These results are similar to those reported in a study performed in 199 HIV + patients in Uganda; 50% of the sample were males, among whom 2% had low BMD in the left hip, compared with 18% in the spine [ 18 ]. In 2018–2019, a study carried out at our hospital, which included 48 women with HIV + and a history of cancer, osteoporosis in the lumbar spine was documented in 47.9% and in the femoral neck in 12.5%compared with healthy women in whom osteoporosis was documented in 14.6% in spine and 0% in femoral neck [ 19 ]. Osteoporosis and the high risk of fractures has also been reported [ 7 ]. In addition, a study conducted in Mexico City investigated the prevalence of vertebral fractures in 104 patients with HIV over 40 years of age (85% men), documenting that 25% had vertebral fractures, and no association was found with ARV drugs or with higher viral loads (> 100,000 copies/mL) [ 20 ]. However, the history of fractures in our population was low (1.2%), although the mean follow-up time was 9.7 ± 6.8 years. Earlier studies have found that age older than 50 years, tobacco consumption, low BMI, and CD4 + lymphocytes < 350 cells/mL were associated with bone abnormalities in men [ 13 , 21 ]. Previously, it was hypothesized that HIV-positive patients under the age of 50 years may have a lower BMD compared to that of HIV-uninfected patients [ 22 ]. We did not find an association between BMD and other risk factors, such as weight loss higher than 10% at HIV diagnosis, age, physical activity, or tobacco consumption. In HIV + patients, the initiation of cART is associated with a 2–6% reduction in BMD [ 23 ]. TDF is directly related to more renal and bone toxic effects compared to Tenofovir Alafenamide (TAF). In a study that analyzed 1,733 patients, 866 received TAF and 867, TDF for 48 weeks; patients with TAF had a minor decrease in BMD in spine and hip [ 24 ]. Loss of BMD is also related to other ARV, such as PI, because this group of drugs affects vitamin-D metabolism, increasing the risk of vitamin-D deficiency [ 25 – 27 ]. We did not find an association between PI or TDF with low BMD, but NNRTI were found as a protective factor. These findings are in contrast with previous published data, which had revealed an association between Efavirenz and low vitamin-D levels, as Efavirenz reduces the expression of cytochrome P450 2RI, which is involved in the 25-hydroxylation of vitamin D, thus the promotion of the conversion of vitamin D into its inactive metabolites [ 28 ]. Previous reports noted that low CD4 + were associated with osteoporosis and osteopenia [ 6 , 17 ]. We found that patients with baseline CD4 + counts of less than 100 cells/mL, compared with those with a higher lymphocyte count, were associated with a higher prevalence of osteoporosis and osteopenia (55.6% vs. 44.4%, respectively; p = 0.05), but this difference was not confirmed in the multivariate analysis. Higher viral loads may indicate a potential role of the virus itself, related with persistent chronic inflammation and low BMD [ 17 , 29 ]. In this study, we did not find that baseline or current viral loads were associated risk factors. An interesting finding comprised that disseminated KS was related as a protective risk factor for low BMD. This may be due to that, because of the severity of the disease, these patients undergo a very close clinical follow-up, rendering it possible to treat opportunistic infections and comorbidities early, and at the same time to carry out screening studies more frequently than in patients with localized disease. The major strengths of this study are that the population included was a captive and homogeneous population of patients with a long follow-up period and a prolonged use of cART. At this time, to our knowledge, this is the first study to evaluate BMD in male HIV-infected patients with a history of KS. Our study limitations lie in that, because it is a cross-sectional study, performed at a single site, the results cannot be extrapolated to different populations. We also did not measure the level of 25-hydroxyvitamin D (25-OF-D), which has a significant effect on bone [ 22 ]. Conclusions The decrease in BMD reported in this cohort in a population of MSM with a history of KS is observed at earlier ages than in those reported in the literature. It is important to perform control DXO, particularly in those exposed to ARV for more than 3 years, regardless of the age of the patients. Declarations Acknowledgment We gratefully acknowledge the X-ray technicians who performed DXA. Declarations Funding This study did not have funding. Conflict of Interest The authors declare there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. Ethics approval The study was approved by the Institutional Ethics Committee (REF/INCAN/CI/0481/2021). Consent to participate Not applicable. DXO performed in the sample was performed as part of routine screening. Consent for publication All authors reviewed the manuscript and consent it for publication. Availability of data and material The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Code availability Not applicable. Authors’ contribution WOO: data collection, and methodology; PVF: Writing and supervision; PCJ: Conceptualization, formal analysis and writing. References Negredo E, Domingo P, Ferrer E, Estrada V, Curran A, Navarro A, et al. Peak bone mass in young HIV-infected patients compared with healthy controls. J Acquir Immune Defic Syndr. 2014;65:207–12. Kruger MJ, Nell TA. Bone mineral density in people living with HIV: a narrative review of the literature. AIDS Res Ther. 2017;14:35. doi: 10.1186/s12981-017-0162-y . Carvalho EH, Gelenske T, Bandeira F, Albuquerque Mda F. Bone mineral density in HIV-infected women taking antiretroviral therapy: a systematic review. Arq Bras Endocrinol Metabol. 2010;54:133–42. Mahy M, Autenrieth CS, Stanecki K, Wynd S. 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Carr A, Grund B, Neuhaus J, Schwartz A, Bernardino JI, White D, et al, International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Prevalence of and risk factors for low bone mineral density in untreated HIV infection: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015;16(Suppl 1):137–46. Negredo E, Langohr K, Bonjoch A, Pérez-Alvárez N, Estany C, Puig J, et al. High risk and probability of progression to osteoporosis at 10 years in HIV-infected individuals: the role of PIs. J Antimicrob Chemother. 2018;73:2452–59. Childs K, Welz T, Samarawickrama A, Post FA. Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients. AIDS. 2012 Jan 28;26(3):253 – 62. Aydın OA, Karaosmanoglu HK, Karahasanoglu R, Tahmaz M, Nazlıcan O. Prevalence and risk factors of osteopenia/osteoporosis in Turkish HIV/AIDS patients. Braz J Infect Dis. 2013;17:707–11. 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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-1626275","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":127902996,"identity":"6a8d0d68-5302-43db-b152-eb884355d857","order_by":0,"name":"Patricia Cornejo-Juárez","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYDADxgbmA0CCKLXMMC1sCSRqYWDgMSBOizn7+YMfPu65I8fc3vNN4ucOGzkG9sNHN+DTYtmTzCw549kzY8aes9ske8+kGTPwpKXdwKfF4EAyGzPPgcOJjTNyt0nwth1ObJDgMcOv5fxjsJb6xhk5zyT/EqXlBsSWBMYZOWzSRNliOeOxseSMA4cNG3uOGVvLtqUZsxHyizl/4sMPHw4cljdsb354822bjRw/++Fj+B0GYxg2MLBIgBhs+JSjaJEHRuoHQqpHwSgYBaNgZAIAbZFNQq5DmTIAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-6331-8372","institution":"Instituto Nacional de Cancerología: Instituto Nacional de Cancerologia","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Patricia","middleName":"","lastName":"Cornejo-Juárez","suffix":""}],"badges":[],"createdAt":"2022-05-05 13:37:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1626275/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1626275/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":25150851,"identity":"b6dff0b6-4652-4c2b-9f92-3b5451488e2b","added_by":"auto","created_at":"2022-08-12 16:40:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":255760,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1626275/v1/853011a9-eeca-4d76-8e90-23a58326cbe0.pdf"}],"financialInterests":"","formattedTitle":"Incidence of osteoporosis and osteopenia in men with HIV+ and a history of Kaposi sarcoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOsteoporosis is characterized by low Bone Mineral Density (BMD) and the microarchitectural deterioration of bone tissue, with an increase in bone fragility and risk of pathological fractures. It is currently considered the most common metabolic disease, causing morbidity and disability [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBMD decreases after the age of 30 years in both women and men, with a much more rapid rate of bone loss in women during perimenopause and early menopause; the risk can vary up to 10-fold depending on the country-of-origin, and other risk factors include vitamin D deficiency, smoking, high alcohol consumption, corticosteroid therapy, lifestyle, weight loss, chronic inflammation, hypogonadism, and HIV chronic infection [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOver the past 25 years, there has been an increase in the life expectancy in HIV population with access to combined Antiretroviral Therapy (cART), which has led to an increase in chronic degenerative diseases to a higher extent than in general population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. BMD loss is a common complication of chronic HIV infection and its therapy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Rates have been reported of between 30 and 67% for osteopenia and of between 15 and 30% for osteoporosis, corresponding to an Odds Ratio (OR) of 6.4 for osteopenia and of 3.7 for osteoporosis when compared with HIV-uninfected individuals [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. There are reports that showed a higher incidence in patients receiving Tenofovir Disoproxil Fumarate (TDF) or Protease Inhibitors (PI) containing cART regimes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eKaposi Sarcoma (KS) is an angioproliferative disease caused by Human Herpes Virus-8 (HHV-8); this virus possesses genes that mimic human oncogenes and codify for the inflammation, proliferation, and differentiation of spindle cells. HHV-8 conditions high levels of circulating cytokines, which are related with chronic inflammation, a recognized factor for BMD loss [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prevalence of low BMD has not been studied in HIV-infected patients with a history of KS. The aim of the study was to evaluate the prevalence of osteopenia and osteoporosis in a cohort of HIV-positive men with a history of KS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e A retrospective study was performed from January 2019 to March 2021, in HIV-positive men with a history of KS who were followed at the HIV/AIDS Cancer Clinic of the Instituto Nacional de Cancerolog\u0026iacute;a in Mexico City, Mexico.\u003c/p\u003e \u003cp\u003eThe HIV/Cancer Clinic was founded in 1990; since then, 1,365 patients have been treated. During the study period, there were 480 patients who were attended distributed as 384 (80%) men and 96 (20%) women. The main neoplasm in HIV-men at our institution is KS, with a mean of 55 new cases per year during the last 5-year period, mainly in men who have sex with men (MSM). We included all HIV-infected men older than 30 years who had received at least 3 years of cART, with a diagnosis of KS, who had a Dual X-ray Absorptiometry (DXA) performed within the last 12 months. The size of the sample was determined by convenience.\u003c/p\u003e \u003cp\u003eExclusion criteria were patients who had received drugs that can alter BMD (such as Prednisone, bisphosphonates, and calcium), those who had received pelvic radiotherapy, had a hip prosthesis, or if data were incomplete in the clinical chart.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eInformed consent\u003c/strong\u003e \u003cp\u003efor patients was waived because the study was retrospective, DXA is part of the studies requested for follow-up, and confidentially is preserved for all patients. The study was approved by the Ethics Committee (REF/INCAN/CI/0481/2021).\u003c/p\u003e \u003c/p\u003e \u003cp\u003eDemographic and clinical data were recorded from clinical charts, included age, date of HIV diagnosis, date of cART initiation, type of cART (classified as Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI), PI, TDF, and Integrase Strand Transfer Inhibitors [INSTI]), baseline CD4\u0026thinsp;+\u0026thinsp;lymphocyte count and viral load, last CD4\u0026thinsp;+\u0026thinsp;and viral load performed prior to the DXA study, date of KS diagnosis, and extension of KS (cutaneous, gastrointestinal, lung, lymph nodes, and lymphedema) were documented and classified as localized or disseminated KS. Disseminated KS was defined as the presence of KS pulmonary disease and/or \u0026ge;\u0026thinsp;30 KS skin lesions, with or without lymphedema, and/or lymph-node involvement, and/or gastrointestinal tract (GIT) KS involvement. The use, type, and number of chemotherapy cycles were recorded. Risk factors for osteoporosis included smoking habits, alcohol use, drug abuse, Body Mass Index (BMI), physical activity documented in Metabolic Equivalents (METS), and history of fractures.\u003c/p\u003e \u003cp\u003ePhysical activity was classified as follows: inactive- no activity; low- light or moderate activity\u0026thinsp;\u0026lt;\u0026thinsp;150 min per week; medium- moderate or vigorous activity 150 to 300 min per week, and as high- vigorous activity, more than 300 min per week [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBMD was measured by DXA (Hologic X-ray Bone Densitometer Discovery\u0026trade; QDR\u0026trade; (Hologic, Inc., Waltham, MA, USA). APEX ver. 4.5.3 software programmed for Hispanic race was used. Quantitative measurement of bone mass referring to the amount of mineral matter (calcium) in grams per square centimeter (gr/cm\u003csup\u003e2\u003c/sup\u003e) was conducted at lumbar spine (L1-L4) and both femoral necks.\u003c/p\u003e \u003cp\u003eAccording to the World Health Organization (WHO), BMD was expressed in relation to a mean reference for young adult female Caucasians (T-score) and grouped accordingly as either normal, osteopenia, or osteoporosis.\u003c/p\u003e \u003cp\u003eWHO-established criteria were employed as follows [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eOsteoporosis: BMD\u0026thinsp;\u0026ge;\u0026thinsp;2.5 Standard Deviations (SD) of the T-score.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eOsteopenia: An intermediate category of bone loss defined as a T-score between \u0026minus;\u0026thinsp;1 and \u0026minus;\u0026thinsp;2.5 SD.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNormal BMD: T-score between 1.0 and \u0026minus;\u0026thinsp;0.9 SD at all three sites.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThe Z-score was used in patients younger than 50 years of age.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe student \u003cem\u003et\u003c/em\u003e test or the Chi\u003csup\u003e2\u003c/sup\u003e test was utilized to compare means for continuous and categorical variables, respectively, among the groups. Variables with a \u003cem\u003ep\u003c/em\u003e value of \u0026lt;\u0026thinsp;0.2 were included in the multivariate logistic regression analysis. Exposure to different ART drugs was analyzed in study participants who received\u0026thinsp;\u0026ge;\u0026thinsp;3 years of the same drugs. Odds Ratios (OR) with 95% Confidence Intervals (95% CI) were calculated. \u003cem\u003eP\u003c/em\u003e values of \u0026le;\u0026thinsp;0.05 were considered statistically significant. Data were analyzed employing STATA (ver. 14) statistical software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 123 men with HIV and KS were seen at the HIV/AIDS Clinic. Among these, 105 had received cART for at least 3 years or were older than 30 years of age. There were 17 patients who did not have a DXA performed, and four were lost to follow-up. Eighty-four patients were included; mean age was 45.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8 years, and 53 patients (63.1%) were younger than 50 years of age. Seventeen patients (20.2%) had a documented BMI of \u0026lt;\u0026thinsp;19 kg/m\u003csup\u003e2\u003c/sup\u003e at HIV diagnosis, and 28 (33.3%) had lost\u0026thinsp;\u0026gt;\u0026thinsp;10% of weight prior to HIV diagnosis. Other clinical data are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline demographic and clinical characteristics in 84 HIV-infected patients with Kaposi sarcoma\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eN\u003c/em\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years) (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.D.)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;40\u003c/p\u003e \u003cp\u003e41\u0026ndash;50\u003c/p\u003e\u003cp\u003e51\u0026ndash;60\u003c/p\u003e\u003cp\u003e\u0026gt;\u0026thinsp;50\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (26.2)\u003c/p\u003e \u003cp\u003e35 (41.7)\u003c/p\u003e \u003cp\u003e22 (26.2)\u003c/p\u003e \u003cp\u003e5 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003csup\u003eb\u003c/sup\u003e \u0026lt;19 (kg/m\u003csup\u003e2\u003c/sup\u003e) at HIV diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (20.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;10% of weight loss at HIV diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh blood pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow or mild physical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (79.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (54.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (history or current)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.42 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of recreational drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (27.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious fractures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIV diagnosis (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasal CD4\u0026thinsp;+\u0026thinsp;cell/mL (median, IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102 (40, 216)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline CD4\u0026thinsp;+\u0026thinsp;cell/mL\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;100\u003c/p\u003e \u003cp\u003e100\u0026ndash;200\u003c/p\u003e \u003cp\u003e201\u0026ndash;300\u003c/p\u003e \u003cp\u003e\u0026gt;\u0026thinsp;300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (49.4)\u003c/p\u003e \u003cp\u003e18 (22.2)\u003c/p\u003e \u003cp\u003e14 (17.3)\u003c/p\u003e \u003cp\u003e9 (11.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline HIV-viral load copies/mL\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143 582 (26 527, 341 500)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLast CD4\u0026thinsp;+\u0026thinsp;cell/mL\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e361 (225, 518)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLast CD4 cell/mL\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;100\u003c/p\u003e \u003cp\u003e100\u0026ndash;200\u003c/p\u003e \u003cp\u003e201\u0026ndash;300\u003c/p\u003e \u003cp\u003e\u0026gt;\u0026thinsp;300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4.7)\u003c/p\u003e \u003cp\u003e13 (15.5)\u003c/p\u003e \u003cp\u003e14 (16.7)\u003c/p\u003e \u003cp\u003e53 (63.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndetectable current viral load\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80 (95.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDF\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (66.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTDF (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (27.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePI (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNNRTI\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (45.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNNRTI (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINSTI\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINSTI (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime from Kaposi sarcoma diagnosis (years)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKaposi sarcoma involvement\u003c/p\u003e \u003cp\u003eSkin\u0026thinsp;\u0026ge;\u0026thinsp;30 lesions\u003c/p\u003e \u003cp\u003eLymph nodes or lymphedema\u003c/p\u003e \u003cp\u003eMouth mucosal involvement\u003c/p\u003e \u003cp\u003eGastrointestinal tract\u003c/p\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (48.8)\u003c/p\u003e \u003cp\u003e13 (15.5)\u003c/p\u003e \u003cp\u003e27 (32.1)\u003c/p\u003e \u003cp\u003e45 (53.6)\u003c/p\u003e \u003cp\u003e5 (5.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisseminated Kaposi sarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (45.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003cp\u003eBleomycin/Vincristine\u003c/p\u003e \u003cp\u003eLiposomal Doxorubicin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (42.8)\u003c/p\u003e \u003cp\u003e35 (97.2)\u003c/p\u003e \u003cp\u003e1 (2.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian number of chemotherapy cycles\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2, 6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003csup\u003ea\u003c/sup\u003eS.D: Standard Deviation; \u003csup\u003eb\u003c/sup\u003eBMI: Body Mass Index; \u003csup\u003ec\u003c/sup\u003eData were available for 81 patients; \u003csup\u003ed\u003c/sup\u003eMedian (Interquartile range); \u003csup\u003ee\u003c/sup\u003eTDF: Tenofovir Disoproxil Fumarate; \u003csup\u003ef\u003c/sup\u003ePI: Protease Inhibitors; \u003csup\u003eg\u003c/sup\u003eNNRTI: Non-Nucleoside Reverse Transcriptase Inhibitors; \u003csup\u003eh\u003c/sup\u003eINSTI: Integrase Strand Transfer Inhibitor.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRegarding HIV-related risk factors, mean time from HIV diagnosis was 9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 years. Median CD4\u0026thinsp;+\u0026thinsp;lymphocyte count at baseline was 102 cells/mL (IQR 40, 216), and median viral load was 143 582 copies/mL (IQR 26 527, 341 500). At the time of DXO, the median CD4\u0026thinsp;+\u0026thinsp;count was 361 cell/mL (IQR 225, 518); 80 (95.2%) patients had an undetectable HIV viral load, the remaining four patients had 116, 138, 976, and 1,014 copies/mL, all related with poor cART adherence. Regarding cART, all patients received NRTI as backbone. Considering those patients who received treatment for \u0026ge;3 years, 56 patients (66.8%) had TDF, 23 (27.4%) PI, 38 (45.2%) NNRTI, and 16 (19%), INSTI. Further clinical data are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eKS was diagnosed with a mean time of 8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 years; in 38 patients (45.2%), KS was classified as disseminated. Thirty-six (42.8%) patients received chemotherapy, median cycles were three (IQR 2\u0026ndash;6), and all received Bleomycin and Vincristine except for one patient, who received two cycles of liposomal Doxorubicin).\u003c/p\u003e \u003cp\u003eAccording to DXA femoral-neck measurements, eight patients (9.5%) had osteoporosis, 35 (41.7%) osteopenia, and 41 (48.8%) had a normal BMD. In lumbar-spine measurements, 20 (23.8%) had osteoporosis, 45 (53.6%) osteopenia, and 19 (22.6%) had normal BMD. A major decrease was observed in lumbar spine (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0007). There were more patients with normal measurements (both in femoral and in spine). Data are depicted in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMale HIV-infected patients with Kaposi sarcoma who received\u0026thinsp;\u0026ge;\u0026thinsp;3 years of different antiretrovirals drugs, according to the DXA result\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeasurement site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDXA result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNNRTI\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;38, 45.2%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-NNRTI\u003csup\u003ea\u003c/sup\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;46, 54.8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePI\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;23, 27.4%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNon-PI\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;61, 72.6%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTDF\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;56, 66.7%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNon-TDF\u003csup\u003ec\u003c/sup\u003e (28, 33.3%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eINSTI\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;16, 19%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNon-INSTI\u003csup\u003ed\u003c/sup\u003e (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;68, 81%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFemoral neck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;41, 48.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (41.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e10 (43.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e31 (50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e27 (48.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e14 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e33 (48.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOsteopenia (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;35, 41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e11 (47.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e24 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e25 (44.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e7 (43.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e28 (41.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOsteoporosis (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;8, 9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e6 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1 (6.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSpine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19, 22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (13.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e7 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3 (18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e16 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOsteopenia (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;45, 53.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (67.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17 (73.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e25 (47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e29 (51.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e16 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e35 (51.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOsteoporosis (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;20, 23.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (13.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15 (26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3 (18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e17 (25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003e. \u003csup\u003ea\u003c/sup\u003eNNRTI: Non-Nucleoside Reverse Transcriptase Inhibitors; \u003csup\u003eb\u003c/sup\u003ePI: Protease Inhibitors; \u003csup\u003ec\u003c/sup\u003eTDF: Tenofovir Disoproxil Fumarate; \u003csup\u003ed\u003c/sup\u003eINSTI: Integrase Strand Transfer Inhibitor.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMain risk factors for low BMD, including type and time of the different ARV drugs, were analyzed comparing normal vs. osteoporosis and osteopenia. NNRTI were associated with less BMD loss.\u003c/p\u003e \u003cp\u003eIn the multivariate analysis, having received NNRTI (OR 0.259, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04) and having disseminated KS (OR 0.12, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) were found as protective factors for osteoporosis and osteopenia. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e demonstrates the univariate and multivariate analyses.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analysis for osteoporosis and osteopenia in 84 HIV\u0026thinsp;+\u0026thinsp;patients with Kaposi sarcoma.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal DXA\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19, 22.6%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOsteoporosis/Osteopenia (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;65, 77.4%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge 30 to \u0026lt;\u0026thinsp;50 years\u003c/p\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;50 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (73.7)\u003c/p\u003e \u003cp\u003e5 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (60)\u003c/p\u003e \u003cp\u003e26 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10% weight loss at HIV diagnosis\u003c/p\u003e \u003cp\u003e\u0026ge;\u0026thinsp;10% of weight loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (63.2)\u003c/p\u003e \u003cp\u003e7 (36.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (67.7)\u003c/p\u003e \u003cp\u003e21 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.784\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate or strong physical activity\u003c/p\u003e \u003cp\u003eLow or mild physical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5.3)\u003c/p\u003e \u003cp\u003e18 (94.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (24.6)\u003c/p\u003e \u003cp\u003e49 (75.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.159 (0.01\u0026ndash;1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNever smoked\u003c/p\u003e \u003cp\u003eCurrent or history of smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (47.4)\u003c/p\u003e \u003cp\u003e10 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (50.8)\u003c/p\u003e \u003cp\u003e32 (49.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline CD4 count\u0026thinsp;\u0026gt;\u0026thinsp;100\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBaseline CD4 count\u0026thinsp;\u0026le;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (70.6)\u003c/p\u003e \u003cp\u003e5 (26.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (44.4)\u003c/p\u003e \u003cp\u003e35 (55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2.18 (0.52\u0026ndash;9.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.284\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline HIV viral load\u0026thinsp;\u0026lt;\u0026thinsp;100,000\u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBaseline HIV viral load\u0026thinsp;\u0026gt;\u0026thinsp;100,000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (50)\u003c/p\u003e \u003cp\u003e7 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (34.6)\u003c/p\u003e \u003cp\u003e34 (65.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLast CD4 count\u0026thinsp;\u0026gt;\u0026thinsp;200\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eLast CD4 count\u0026thinsp;\u0026lt;\u0026thinsp;200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (78.9)\u003c/p\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (78.5)\u003c/p\u003e \u003cp\u003e14 (21.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-TDF or TDF\u0026thinsp;\u0026lt;\u0026thinsp;3 years\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTDF\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (36.8)\u003c/p\u003e \u003cp\u003e12 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (32.3)\u003c/p\u003e \u003cp\u003e44 (67.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.784\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-PI or PI\u0026thinsp;\u0026lt;\u0026thinsp;3 years\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePI\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (84.2)\u003c/p\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (69.2)\u003c/p\u003e \u003cp\u003e20 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-NNRTI or NNRTI\u0026thinsp;\u0026lt;\u0026thinsp;3 years\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNNRTI\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (36.8)\u003c/p\u003e \u003cp\u003e12 (63.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (60)\u003c/p\u003e \u003cp\u003e26 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.259 (0.07\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-INSTI or INSTI\u0026thinsp;\u0026lt;\u0026thinsp;3 years\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eINSTI\u0026thinsp;\u0026ge;\u0026thinsp;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (84.2)\u003c/p\u003e \u003cp\u003e3 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (80)\u003c/p\u003e \u003cp\u003e13 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocalized Kaposi sarcoma\u003c/p\u003e \u003cp\u003eDisseminated Kaposi sarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003cp\u003e15 (78.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (64.6)\u003c/p\u003e \u003cp\u003e23 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.12 (0.03\u0026ndash;0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-comorbidities\u003c/p\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (26.3)\u003c/p\u003e \u003cp\u003e14 (73.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (52.3)\u003c/p\u003e \u003cp\u003e31 (47.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0.422 (0.1\u0026ndash;1.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003eFour patients did not have baseline CD4 in their clinical chart; \u003csup\u003eb\u003c/sup\u003ecells/mL; \u003csup\u003ec\u003c/sup\u003eEighteen patients did not have viral load; \u003csup\u003ed\u003c/sup\u003eCopies/mL; \u003csup\u003ee\u003c/sup\u003eTDF: Tenofovir Disoproxil Fumarate; \u003csup\u003ef\u003c/sup\u003ePI: Protease Inhibitors; NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitors; \u003csup\u003eh\u003c/sup\u003eINSTI: Integrase Strand Transfer Inhibitor.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMany studies have investigated the prevalence of osteoporosis and osteopenia in HIV-positive patients. However, this is to our knowledge, the first study performed in a cohort of 84 MSM with a history of KS who received cART for more than 3 years and with an age of \u0026ge;\u0026thinsp;30 years (67.8% were younger than 50 years of age). This study found a rate of osteopenia (53.6%) and osteoporosis (23.8%), similar to those in previous reports carried out in patients with HIV infection, but considerably higher than those reported in male population without HIV. In a study carried out between 2000 and 2009, that included 73% males, 49.6% was reported of osteopenia and 21.7% of osteoporosis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Another study conducted in 2017, which included 108 patients with HIV (79 were males), it was reported that 23% of those studied had low BMD [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The current guidelines do not recommend the measurement of BMD in HIV-infected patients younger than 50 years of age [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. We included patients who have been receiving ARV treatment for at least 3 years, and although there were no differences between younger (\u0026lt;\u0026thinsp;50 years, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;53) and older (\u0026ge;\u0026thinsp;50 years, \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;31) patients, osteopenia and osteoporosis were considerably high in young patients (39/53, 73.6%).\u003c/p\u003e \u003cp\u003eBMD loss may be the result of complex interactions between HIV infection and/or long-term cART and patient lifestyle-related factors [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The risk factors for osteoporosis are classified as unmodifiable, modifiable, and secondary causes. Unmodifiable risk factors include older age, feminine gender, family history of osteoporosis, and history of previous fractures. Modifiable risk factors include low BMI, tobacco use, poor physical activity, use of long-term glucocorticoid treatment, long-term anticonvulsant therapy, excessive use of alcohol, and a low dietary intake of vitamin D or calcium. Secondary causes include type 1 diabetes, rheumatoid arthritis, anorexia nervosa, hyperthyroidism, hyperparathyroidism, hypogonadism or premature menopause, chronic malnutrition or malabsorption, and chronic liver disease [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn general population, osteoporosis in men is predominantly in cortical-bone tissue (hip area), while for HIV\u0026thinsp;+\u0026thinsp;patients, osteoporosis preferably affects trabecular bone, especially involving the lumbar spine [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In our study, a lower BMD was found predominantly in lumbar spine (77.4%) compared with femoral neck (51.2%). These results are similar to those reported in a study performed in 199 HIV\u0026thinsp;+\u0026thinsp;patients in Uganda; 50% of the sample were males, among whom 2% had low BMD in the left hip, compared with 18% in the spine [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In 2018\u0026ndash;2019, a study carried out at our hospital, which included 48 women with HIV\u0026thinsp;+\u0026thinsp;and a history of cancer, osteoporosis in the lumbar spine was documented in 47.9% and in the femoral neck in 12.5%compared with healthy women in whom osteoporosis was documented in 14.6% in spine and 0% in femoral neck [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOsteoporosis and the high risk of fractures has also been reported [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In addition, a study conducted in Mexico City investigated the prevalence of vertebral fractures in 104 patients with HIV over 40 years of age (85% men), documenting that 25% had vertebral fractures, and no association was found with ARV drugs or with higher viral loads (\u0026gt;\u0026thinsp;100,000 copies/mL) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. However, the history of fractures in our population was low (1.2%), although the mean follow-up time was 9.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 years.\u003c/p\u003e \u003cp\u003eEarlier studies have found that age older than 50 years, tobacco consumption, low BMI, and CD4\u0026thinsp;+\u0026thinsp;lymphocytes\u0026thinsp;\u0026lt;\u0026thinsp;350 cells/mL were associated with bone abnormalities in men [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Previously, it was hypothesized that HIV-positive patients under the age of 50 years may have a lower BMD compared to that of HIV-uninfected patients [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. We did not find an association between BMD and other risk factors, such as weight loss higher than 10% at HIV diagnosis, age, physical activity, or tobacco consumption.\u003c/p\u003e \u003cp\u003eIn HIV\u0026thinsp;+\u0026thinsp;patients, the initiation of cART is associated with a 2\u0026ndash;6% reduction in BMD [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. TDF is directly related to more renal and bone toxic effects compared to Tenofovir Alafenamide (TAF). In a study that analyzed 1,733 patients, 866 received TAF and 867, TDF for 48 weeks; patients with TAF had a minor decrease in BMD in spine and hip [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Loss of BMD is also related to other ARV, such as PI, because this group of drugs affects vitamin-D metabolism, increasing the risk of vitamin-D deficiency [\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. We did not find an association between PI or TDF with low BMD, but NNRTI were found as a protective factor. These findings are in contrast with previous published data, which had revealed an association between Efavirenz and low vitamin-D levels, as Efavirenz reduces the expression of cytochrome P450 2RI, which is involved in the 25-hydroxylation of vitamin D, thus the promotion of the conversion of vitamin D into its inactive metabolites [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious reports noted that low CD4\u0026thinsp;+\u0026thinsp;were associated with osteoporosis and osteopenia [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. We found that patients with baseline CD4\u0026thinsp;+\u0026thinsp;counts of less than 100 cells/mL, compared with those with a higher lymphocyte count, were associated with a higher prevalence of osteoporosis and osteopenia (55.6% vs. 44.4%, respectively; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.05), but this difference was not confirmed in the multivariate analysis. Higher viral loads may indicate a potential role of the virus itself, related with persistent chronic inflammation and low BMD [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In this study, we did not find that baseline or current viral loads were associated risk factors.\u003c/p\u003e \u003cp\u003eAn interesting finding comprised that disseminated KS was related as a protective risk factor for low BMD. This may be due to that, because of the severity of the disease, these patients undergo a very close clinical follow-up, rendering it possible to treat opportunistic infections and comorbidities early, and at the same time to carry out screening studies more frequently than in patients with localized disease.\u003c/p\u003e \u003cp\u003eThe major strengths of this study are that the population included was a captive and homogeneous population of patients with a long follow-up period and a prolonged use of cART. At this time, to our knowledge, this is the first study to evaluate BMD in male HIV-infected patients with a history of KS. Our study limitations lie in that, because it is a cross-sectional study, performed at a single site, the results cannot be extrapolated to different populations. We also did not measure the level of 25-hydroxyvitamin D (25-OF-D), which has a significant effect on bone [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe decrease in BMD reported in this cohort in a population of MSM with a history of KS is observed at earlier ages than in those reported in the literature. It is important to perform control DXO, particularly in those exposed to ARV for more than 3 years, regardless of the age of the patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgment\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge the X-ray technicians who performed DXA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDeclarations\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study did not have funding.\u003c/p\u003e\n\u003cp\u003eConflict of Interest\u003cbr\u003e\u0026nbsp;The authors declare there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.\u003c/p\u003e\n\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Institutional Ethics Committee (REF/INCAN/CI/0481/2021).\u003c/p\u003e\n\u003cp\u003eConsent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable. DXO performed in the sample was performed as part of routine screening.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript and consent it for publication.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCode availability\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contribution\u003c/p\u003e\n\u003cp\u003eWOO: data collection, and methodology; PVF: Writing and supervision; PCJ: Conceptualization, formal analysis and writing.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNegredo E, Domingo P, Ferrer E, Estrada V, Curran A, Navarro A, et al. Peak bone mass in young HIV-infected patients compared with healthy controls. 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Braz J Infect Dis. 2013;17:707\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Osteoporosis, Osteopenia, HIV, Kaposi sarcoma, Antiretroviral therapy, Bone Mineral Density (BMD).","lastPublishedDoi":"10.21203/rs.3.rs-1626275/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1626275/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Low bone mineral density (BMD) is a common complication of chronic HIV infection, reported between 30%-67% for osteopenia, and between 15%-30% for osteoporosis. Kaposi Sarcoma (KS) is an angioproliferative disease, mediated by cytokines which contributes to inflammation. The objective was to assess the prevalence of BMD in a cohort of HIV+ men with a history of KS.\u003c/p\u003e\u003cp\u003eMethods: A retrospective study was performed from January 2019 to March 2021, in men over the age of 40 years and/or with more than 3 years of antiretroviral drugs. Odds Ratios with 95% Confidence Intervals were calculated. \u003cem\u003eP\u003c/em\u003e values of ≤0.05 were considered statistically significant. \u003c/p\u003e\u003cp\u003eResults: Eighty-four patients were included; mean age was 45.9 ± 8.8 years, and mean time from HIV diagnosis was 9.7 ± 6.8 years. The median baseline CD4+ was 102 cells (IQR 40, 216), and the median viral load was 143 582 copies/ml (IQR 26 527, 341 500). At the time of Dual X-ray Absorptiometry, the median CD4+ count was 361 cell/mL (IQR 225, 518) and the HIV-viral load was undetectable in 80 patients (95.2%). Osteoporosis was documented in 23.8% and osteopenia in 53.6%. The analysis comparing main risk factors, including different ARV drugs for low BMD did not show statistical differences. \u003c/p\u003e\u003cp\u003eIn the multivariate analysis, NNTRI and disseminated KS were found as protective factors for low BMD. \u003c/p\u003e\u003cp\u003eConclusions: The low BMD reported in this cohort may be related to several risk factors, it is advisable to establish preventive measures for BMD loss, regardless of age.\u003c/p\u003e","manuscriptTitle":"Incidence of osteoporosis and osteopenia in men with HIV+ and a history of Kaposi sarcoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-08-12 16:40:06","doi":"10.21203/rs.3.rs-1626275/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2022-08-10T19:50:49+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-08-10T09:59:07+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-08-10T08:50:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2022-08-09T21:53:46+00:00","index":"","fulltext":""},{"type":"decision","content":"Major revisions","date":"2022-08-09T06:28:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"73295ea9-af8e-4111-8367-4a4fd09ccfa6","owner":[],"postedDate":"August 12th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-09-20T12:02:20+00:00","versionOfRecord":[],"versionCreatedAt":"2022-08-12 16:40:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1626275","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1626275","identity":"rs-1626275","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}