Evaluation of a Modified Short all oral Treatment Regimen for Rifampicin-Multidrug Resistant Tuberculosis in Dominican Republic

Evaluation of a Modified Short all oral Treatment Regimen for Rifampicin-Multidrug Resistant Tuberculosis in Dominican Republic | 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 Evaluation of a Modified Short all oral Treatment Regimen for Rifampicin-Multidrug Resistant Tuberculosis in Dominican Republic María Rodríguez, Yamile Celis Bustos, Melanea Encarnación, Elisabet Muñoz, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4271608/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Feb, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 4 You are reading this latest preprint version Abstract Background This study aims to evaluate the effectiveness, safety, and impact on health-related quality of life (HQoL) of a fully oral shortened regimen for Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) over 9 to 12 months under programmatic conditions. Methods A prospective cohort study was conducted on an all-oral modified Shortened Treatment Regimen (mSTR) comprising linezolid (Lzd), bedaquiline (Bdq), levofloxacin (Lfx), clofazimine (Cfz), and cycloserine (Cs). Patients with RR/MDR-TB were enrolled between January and December 2022 across seven drug-resistant TB units in the Dominican Republic. Results A total of 113 patients were enrolled, with 87% achieving culture conversion at two months. Treatment outcomes revealed that 79% of patients were successfully treated and didn’t relapse six months after the end of the treatment, 14% were lost to follow-up during the treatment, 6% deceased, and one experienced treatment failure due to Adverse Drug Reactions (ADRs). Adverse events (AEs) were common, with 82% of patients experiencing at least one AE with high proportion of QT interval prolongation, elevated transaminases, and anemia. A total of 12% of the patients experiencing Serious Adverse Events (SAEs). Improvement in HQoL dimensions was noted throughout treatment, with the EQ-VAS score increasing by an average of 15.5 by treatment end. Conclusion The high treatment success rate of the 5-drug mSTR facilitated the adaptation and integration of a shortened treatment regimen lasting 9 to 12 months in routine care in Dominican Republic. Although AEs were frequent, they were manageable in most cases. Continuous monitoring, especially regarding Lzd and Bdq use, is crucial to effectively mitigate risks. Since September 2023, this short all oral treatment regimen is now the one recommended for RR/MDR-TB patients in Dominican Republic. Tuberculosis Multidrug-Resistant bedaquiline Linezolid Short all-oral treatment Treatment Outcome Safety Health-Related Quality of Life Dominican Republic Figures Figure 1 Figure 2 INTRODUCTION Tuberculosis (TB), one of the most prevalent infectious diseases globally, continues to exert a significant burden on mortality and morbidity. In 2022 TB ranked as the second- largest infectious killer worldwide, surpassed only by coronavirus disease (COVID-19). It was reported as the primary cause of death among people with the human immunodeficiency virus (HIV) and a significant contributor to deaths related to antimicrobial resistance[ 1 ]. In 2022, the global estimate for cases of multidrug resistant or rifampicin-resistant TB (RR/MDR-TB) was 410,000. In the Region of the Americas, approximately 12,000 cases of RR/MDR-TB were estimated, constituting an estimated proportion of 3.2% (2.1–4.4) of new cases, with 5,444 cases reported [ 2 ]. The Dominican Republic has consistently ranked among the top five countries with the highest MDR-TB rate in the Region of the Americas since the publication of the first national surveillance report in 1998 [ 3 ]. With a drug susceptibility testing (DST) coverage of 89% and an estimated proportion of 6.8% (6-7.7) among new cases, the Dominican Republic reported 185 cases RR/MDR-TB out of 4,306 notified in 2022 [ 2 ]. Between 2006 and 2008, cohorts on standardized regimens achieved a success rate of 74% at national level [ 4 ]. These regimens covered periods of 18–24 months, with injectable drugs administered for six months. From 2014, the decentralization process and an outpatient model of care for RR/MDR-TB was introduced, maintaining regimens with injectables. However, there was a decline in treatment success from 74–60%, mainly attributed to high rates of patients lost to follow-up (28–35%). Following the World Health Organization (WHO) recommendation of an all-oral treatment regimen[ 5 , 6 ], the success rate increased from 60–75% in 2020. This was due to a decrease of the lost to follow-up rate to 18% by 2020. Nevertheless, additional measures needed to be taken to further decrease the percentage of patients lost to follow-up and improve overall success rate for all patients [ 2 , 7 ]. Shortening the length of the treatment was felt as a key strategy to consider. Since 2020, the national TB control program (NTCP) of the Dominican Republic, in collaboration with the Special Programme for Research and Training in Tropical Diseases (TDR) of the World Health Organization (WHO) and the Pan American Health Organization (PAHO), has been conducting operational research on the effectiveness, safety, and impact on health-related quality of life (HQoL) of RR/MDR-TB patients treated with the modified Short all oral Treatment Regimen (mSTR) for drug-resistant TB patients[ 8 ].The introduction of a fully oral modified short treatment regimen holds significant potential to reduce the duration of treatment, enhance treatment compliance, and ultimately increase the success rate of treatment[ 2 , 9 ]. The five-drug WHO-recommended STR has been in implementation since February 2022[ 8 ]. Our objective was to evaluate the effectiveness, safety, and impact on HQoL of this 9 to 12 month fully oral shortened RR/MDR-TB under programmatic conditions. In this paper, we present end-of-treatment and follow up outcomes at three and six months after the end of the treatment. This study also aimed to guide RR/MDR-TB treatment policy for Dominican Republic. METHODS Study design. A prospective cohort study was conducted that enrolled patients with RR/MDR-TB between January and December 2022 in seven drug-resistant TB units in the Dominican Republic[2]. The research protocol and data collection tools were developed using the Short all-Oral Regimens for Rifampicin-resistant Tuberculosis (ShoRRT) research package proposed by TDR [8], and adapted to the context of the country. Study population. The study population comprised of TB patients with evidence of resistance to at least rifampicin (R) detected by the molecular WHO-recommended rapid diagnostic test for TB (mWRD), Xpertâ MTB/RIF Ultra, or conventional (culture-based) drug susceptibility testing (DST). For minors (18 years of age and younger), inclusion criteria involved confirm TB case without DST but close contact with a confirmed RR/MDR-TB case. The total expected number of patients depended on those meeting the specified criteria in the country during 2022. Isoniazid (H) and Fluoroquinolone (FQ) susceptibility were assessed by Line Probe Assay (LPA) and/or phenotypic DST. The main exclusion criteria included FQ resistance, inability to take oral medications, allergies, or the use of medications contraindicated with any of the drugs in the mSTR regimen, and a Fredericia-corrected QT interval (QTcF) of ≥ 500 ms at baseline that does not correct with medical treatment. Additionally, patients less than 2 years of age were excluded. Patients who met the inclusion criteria and gave their consent were enrolled in the study as they presented at the health center for treatment during the study period. Study procedures. Short treatment regimen under investigation The study regimen consisted of five drugs: linezolid (Lzd), bedaquiline (Bdq), levofloxacin (Lfx), clofazimine (Cfz), and cycloserine (Cs), at doses calculated by weight according to the recommendation of WHO [9] ( supplementary table S1 ). The initial phase compromised four-months with Lzd-Bdq-Lfx-Cfz-Cs, followed by a two-month continuation phase with Bdq-Lfx-Cfz-Cs, and a three-month maintenance phase with Lfx-Cfz-Cs. The total treatment duration was 9 months with a possible extension to 12 months if the 4 -month sputum culture was positive. Patient follow-up continued for 12 months (3, 6 and 12 months) after the end of the treatment. Evaluation criteria Effectiveness : the proportion of RR/MDR-TB patients with a favorable treatment outcome defined as cured or treatment completed without recurrence at 3, 6 and 12 months after the end of the treatment. Safety : the proportion of RR/MDR-TB patients who experience a serious adverse event up to six-months after the end of the treatment. Health-related Quality of Life (HQoL): HQoL was evaluated using the Euroquol EQ-5D-5L questionnaire[10], a concise, generic measure of self-reported health status. The assessment focused on determining the proportion of patients who experienced an improvement in their quality of life during the treatment period. Investigation plan To evaluate the effectiveness, safety, and impact on the HQoL of the shorter oral treatment regimen implemented in this study, the following parameters were monitored monthly during treatment and six months after the end of the treatment: baseline patient characteristics, clinical evaluation, bacteriology (DST, smear, and culture), laboratory tests (particularly Hemoglobin level), and additional parameters detailed in supplementary Table S2 . Data collection and analysis Data was collected using standardized forms built on the REDCap electronic data capture tool hosted at WHO Geneva[11]. Periodic data cleaning for identifying missing data and inconsistences was performed centrally by the coordinating center of the Dominican Republic national TB programme. Data were collected for the following variables: age in years, gender (male, female), TB treatment history, TB type (pulmonary or extra-pulmonary); TB category (new or previously treated); sputum smear result (smear-positive, smear-negative, smear not done); Mycobacterium tuberculosis culture result (positive, negative, not done); drug susceptibility testing (DST) results if available; treatment start date; sputum culture conversion (Yes, No); date of sputum culture conversion; para-clinical parameters (chest X-ray, electrocardiogram, blood test); final treatment outcome (cured, treatment completed, treatment failed, died, lost to follow up and not evaluated) as defined by WHO[12]; TB recurrence; adverse events and HQoL data. The occurrence of SAEs and Adverse Events of Special Interest related to the drugs used was monitored and reported monthly in accordance with the recommendations of the WHO[13]. These events included blood-related issues, cardiac concerns (such as QTcF prolongation), hepatic complications (Alanine aminotransferase enzyme increase), nervous system disorders (including optic neuritis, peripheral neuropathy) and mental disorders. The severity of adverse events was graded according to the Division of AIDS table for grading the severity of adult and pediatric patients, as outlined by the U.S. National Institutes of Health[14] and for QTc prolongation, the National Cancer Institute Common Terminology of Clinical Adverse Events v5 was utilized[15]. For HQoL assessment, data were collected at enrolment, four months into treatment, at the end of treatment and 12 months after the end of treatment, using the EQ-5D-5L questionnaire[16]. This questionnaire comprises two parts: the EQ-5D-5L, which includes a descriptive system of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) in five levels. Participants indicated for each dimension whether they have no, mild, moderate, severe, or extreme problems. For each dimension, the proportion of patients with no, mild/moderate and severe/extreme problems was determined at each time point. The second part is the EQ-VAS which captures the respondent’s overall assessment of their health on a scale from 0 (worst health) to 100 (best health). Categorical variables were described using frequencies and percentage, while continuous variables were summarized using means with standard deviation or medians with 1 st and 3 rd quartiles. For HQoL data, data analysis, changes in health states for each dimension were determined at four months into treatment and at the end of treatment, alongside mean EQ-VAS scores at baseline and the average difference EQ-VAS score from baseline. Data analyses were performed using STATA software (version 17). Ethics approval The study received ethical approval from the WHO Research Ethics Review Board (Generic Protocol ID: ERC0003305, 08/06/2020) and the Ethics Committee of the Dr. Hugo Mendoza National Center for Research in Maternal and Child Health (CENISMI, 10/07/21). Written informed consent was obtained for all study participants . RESULTS Between January to December 2022, a total of 185 patients with RR/MDR-TB were diagnosed using Xpert MTB/RIF Ultra in seven drug resistant TB units. Sixty-two patients were excluded due to being unlocatable or deceased before treatment initiation, prior use of drugs from the regimen or not available at the program, age under two years, absence of LPA results, known FQ-resistance, or the presence of cardiovascular complications with QTcF >500ms. Of the remaining 123 patients, screening and consultation were conducted for potential inclusion in the modified short treatment regimen (mSTR). Seven were further excluded due to FQ-resistance identified with second-line drug susceptibility testing (SL-DST), two never initiated the mSTR and one withdrew consent ( Figure 1 ). Baseline characteristics of patients A total of 113 patients were included in the effectiveness analysis. among these patients, 80 were male (71%), with a median age of 40 years, and 74 patients (65%) were aged between 25-55 years. Table 1 presents the baseline characteristics of these patients. All patients had confirmed pulmonary rifampicin resistant TB. Among them, 85 (75%) were new patients, while 28 (25%) had prior treatment with first-line drugs, including 16 (14%) classified as relapses. Fourteen patients (12%) were tested positive for HIV, 18 (16%) had diabetes and 7 (6%) had existing neuropathy. A positive sputum culture was observed in 75 out of 113 patients (66%), with DST results available for 72(64%), with 67 being resistant to isoniazid (59% MDR-TB). Seventy-two (64%) patients had DST results confirming fluoroquinolone susceptibility. Among all patients, 71 (63%) had TB cavities, and 25 (22%) had extended lesions (≥ 50%) on chest X-Ray ( Table 1 ). The hematological evaluation revealed a median hemoglobin level of 11.8 g/dL (10.4-13.2) g/dL. Twenty-seven (24%) patients had grade 1 or more anemia (less than 10.5 g/dl) at baseline. Liver function test was within the normal range (AST/SGOT 24(17-36) U/L), except for one patient. No initial alteration of renal function was observed (creatinine 0.83 (0.7-1) mg/dl). The mean value of the body mass index (BMI) was 20.25 (17.95-23.2) kg/m² and the mean value QTcF intervals was 396 (355-437) ms. Regarding HQoL, patients reported problems with physical functioning including mobility (18%), self-care (6%) and usual activity (19%). Additionally, 17% of surveyed patients reported problems with pain/discomfort domain, while anxiety/ depression was reported by 19% of participants. The EQ-VAS score mean was 79 (±14), Treatment outcome Among 113 patients, 89 (79%) had a favorable outcome, defined as being successfully treated without recurrence six months after the end of the treatment. Sixteen patients (14%) were lost to follow up, with three of them lost before completing three months of treatment, and two of these individuals tested negative in cultures. Seven patients (6%) died, and one experienced treatment failure, resulting from a permanent regimen change due to Adverse Drug Reactions (ADRs) ( Table 2 ). Of the 41 patients who did not have fluoroquinolones’ DST results, 34 (83%) had a favorable outcome, three (7%) were lost to follow up and four (10%) died. Among the total patients, 75 had a positive culture at baseline, and 69 had a follow up smear result. Culture conversion in the second month was achieved for 60 patients (87%) ( Figure 2 ). A favorable outcome was obtained with a treatment duration of nine months for 82 (92%) patients, 11 months for 5 patients and 12 months for 2 patients. The reasons for extending treatment beyond nine months were a positive sputum smear at four months of treatment in 3 patients and difficulties in compliance in 4 patients. Adverse events Out of 113 patients, 93 (82%) experienced at least one adverse event (AE) of interest. Fourteen patients (12%) had at least one SAE which resulted in death for seven of them. A total of six SAEs were related to the TB drugs (ADRs). None of the ADRs resulted in death. A total of 237 AEs of special interest were recorded, with 106 (45%) classified as grade 1, 102 (43%) as grade 2, and 27 (11%) as grade 3. Two (1%) of the AEs were Grade 4. The most frequent AEs of special interest included prolonged QTcF in 119 (50%) cases, elevated transaminases in 56 (23%), anemia in 41 (17%), and thrombopenia in 11 (5%). Peripheral neuropathy was found in 6 patients (3%) and none of the patients suffered from optic neuropathy. More details can be found in the Table 3 . Health related Quality of life (HQoL) In all five dimensions, most patients who reported problem at baseline and were evaluated after four months of treatment felt better (73% for mobility, 50% for self-care, 69% for usual activities, 71% for pain/discomfort and 92% for anxiety/depression). At the end of treatment, almost all evaluated patients who had reported problem at baseline felt better (100% for the dimensions mobility and usual activities; 91% for the dimensions pain/discomfort and anxiety/depression). In the dimension of self-care, only two patients with problem at baseline were evaluated with one showing improvement and one showing worsening ( Table 4 ). Regarding the EQ-VAS score, the mean was, 84 (±10.9) at four months of treatment and 96 (±4) at the end of treatment. The mean difference in EQ-VAS score compared to baseline measurement was 3.3(± 9) at four months and 15.5 (±14) at the end of the treatment (Table 4). DISCUSSION This study represents the first investigation conducted in Dominican Republic (DR) to assess the effectiveness, safety, and impact on the health-related quality of life (HQoL) among RR/MDR-TB patients treated with 9–12 months short all oral treatment. The 5-drug all-oral modified short treatment (mSTR) implemented in this study mirrored the long regimen endorsed by the WHO[ 17 ]. It demonstrated a high early conversion rate (87% at 2 months) and a notable treatment success rate (79%) among RR/MDR-TB patients. This treatment success rate is comparable to the one achieved with the longer treatment regimen with the seven-drug STR containing injectable agents for the 2020 MDR-TB cohort (75%). Notable, none of the cured patients experienced relapse six months after the end of treatment, indicating sustained treatment cure [ 7 ]. Our results align with success rates (ranging from 75 to 90%) reported in other countries for RR/MDR-TB patients treated with all oral mSTR[ 18 , 19 ]. Importantly, the treatment success achieved with this simplified mSTR, utilizing Bdq, Lfx and Lzd as core drugs, and Cfz and Cs as companion drugs, appears to provide more favorable outcomes than those found in Central Asia. For instance, In Uzbekistan, a cohort of 95 patients achieved only a 66% success rate using seven-drugs regiment with high dose of H and Mfx as core drug, and without Bdq [ 20 ]. Despite the lack of information on FQ susceptibility in 46 (41%) of the 113 patients, a conversion rate of 87% was achieved at two months. The high conversion and treatment success rate of the mSTR evaluated in this study may be attributed to the potent bactericidal and sterilizing activities of the two main drugs, Bdq and Lfx. Indeed, the use of Lzd has been associated with improved treatment outcomes, as reported by Nguyen in 2023[ 18 ]. Despite a decrease in the percentage of patient’s loss to follow-up in the Dominican Republic compared to previous years, dropping from 18% in 2020 to 14% in this study, there remains a need to strengthen a patient-centered care approach to further improve treatment compliance. Analysis of the baseline and control culture results of patients lost to follow-up indicated a low risk of disease transmission to the community and/or development of bedaquiline resistance. Only one patient's culture status could not be determined. No cases of bacteriological failure were recorded. Treatment modification was necessary for only one patient due to adverse events related to medication use, while seven patients died during treatment from causes unrelated to medication use and comorbidities. Although adverse events (AEs) were common during RR/MDR-TB treatment, most of them were grade 1–2, consistent with findings from other studies[ 21 , 22 ]. The most frequent AE was prolonged QTc interval, reported in 68% of cases, which has been documented in other studies and associated with the use of Bdq and Cfz [ 22 ]. Twelve percent of patients experienced SAEs, with drug-related SAEs observed in 5% of patients. Only one patient required modification in the RR/MDR-TB regimen due to elevated transaminases associated with the use of Bdq and Lzd [ 9 , 22 ]. Anemia-related SAE was the most frequent, observed in 5 patients (4%), and was associated with the use of Linezolid (Lzd). It was identified at a lower proportion in this study compared to other studies reported where higher doses of Lzd were used[ 23 ]. This success may be attributed to the doses of Lzd used in this study (600 mg), which have been demonstrated to mitigate the toxicity associated with this drug[ 24 ]. From a national TB programme perspective, this AE seems to be manageable if carefully monitored. In this study, patients started the treatment with favorable overall conditions, including disease extent, clinical parameters and HQoL evaluations. This may be attributed to early diagnosis facilitated by the utilization of more sensitive rapid molecular tests. The health-related quality of life EQ-VAS score in patient with RR/MDR-TB increased by an average of 16 points at the end of the treatment compared to baseline, indicating a significant enhancement in patients' quality of life throughout the treatment period. These results underscore the high effectiveness of the mSRT used in this study for treating patients with RR/MDR-TB in Dominican Republic. This regimen’s success enabled the shortening of the standardized treatment regimen, which originally had a longer duration, and facilitated an assessment of its impact on patient quality of life. The study demonstrated that this regimen does not impose a negative impact and, in fact, enhances treatment compliance. One of the primary limitations of this research was the limited availability of fluoroquinolone molecular susceptibility testing. This constraint posed challenges in expanding the patient sample, emphasizing the importance of ensuring comprehensive coverage of this diagnostic test for all individuals with RR/MDR TB. Safety profile appears manageable in most patients, with few serious adverse events observed, and very few attributed to medication use. Active Drug Safety Monitoring (aDSM) has been implemented in the Dominican Republic since begin of programmatic MDR-TB management; however, this study emphasizes the necessity to systematize and enhance aDSM in the country. CONCLUSION This operational research study facilitated the evaluation and integration of a shortened treatment regimen lasting 9 to 12 months, utilizing the same drugs as the prolonged treatment regimen proposed by the WHO, tailored to the conditions in the Dominican Republic. This allowed for the adjustment of guidelines, providing an alternative approach for managing patients with RR/MDR-TB in the country. Furthermore, the implementation of this regimen resulted in improved patient compliance due to its shorter duration. Since September 2023, this short all oral treatment regimen is now the one recommended for RR/MDR-TB patients in Dominican Republic. Abbreviations COVID-19: Coronavirus disease HIV: immunodeficiency virus TB: Tuberculosis MDR-TB: Multidrug-Resistant Tuberculosis RR/MDR-TB: Rifampicin-Resistant/Multidrug-Resistant Tuberculosis mSTR: Modified Shortened Treatment Regimen ShoRRT: Short all-Oral Regimens for Rifampicin-resistant Tuberculosis Lzd: Linezolid Bdq: Bedaquiline Lfx: Levofloxacin Cfz: Clofazimine Cs: Cycloserine R: Rifampicin H: Isoniazid FQ: Fluoroquinolone DST: Drug Susceptibility Testing mWRD: molecular WHO-recommended Rapid Diagnostic test for TB LPA: Line Probe Assay ADRs: Adverse Drug Reactions AEs: Adverse events SAEs: Serious Adverse Events QTcF: Fredericia-corrected QT interval HQoL: health-related quality of life NTCP: National Tuberculosis Control Programme TDR: Special Programme for Research and Training in Tropical Diseases WHO: World Health Organization PAHO: Pan American Health Organization Declarations Ethics approval and consent to participate. The study obtained ethical approval from the WHO Research Ethics Review Board and the Ethics Committee of the Dr. Hugo Mendoza National Center for Research in Maternal and Child Health. Informed consent was obtained from each participant or respondent. All methods adhered to relevant guidelines and regulations. Consent for publication. All authors and respondents involved in this research have consented to the publication of all paper details, data, tables, and images. These materials will be freely accessible on the internet. Availability of data and material Data is available within the manuscript. Competing interests The authors declare no competing interests. Authors’ contribution All authors contributed substantially to the conception, design, analysis, and interpretation of data, and participated in the preparation and review of drafts of this manuscript and gave their final consent to the publication of the final version. Funding TDR, the Special Programme for Research and Training in Tropical Diseases, provided technical assistance and catalytic funding (grant 2021/1188581-0) for the conduct of this study as part of the ShORRT initiative. Disclaimer The findings and conclusions of this article are the intellectual responsibility of its authors and do not necessarily represent the official position of Special Programme for Research and Training in Tropical Diseases of World health Organization, the Pan American Health Organization, Nacional Health Service, and Ministry of Public Health of Dominican Republic. Acknowledgements We would like to acknowledge Ricardo Elias Melgen (National TB Program), and Orquídea Moreno (National Reference TB Laboratory) of the Ministry of Health; Rudelina de los Santos, and Yaneiry Cuevas (Clinical Management Department), and the staff of the DR-TB Regional Units for taking the time and effort to contribute to this research, especially to Marika Pérez, Jorge Rodríguez y Nadiezhda Ratchel, as well as Esther López of the National Health Service for his continuous support to this initiative. Our gratitude extends to the participating patients. References Pan American Health Organization. Tuberculosis [Internet]. Pan American Health Organization. 2022 [cited 2023 Dec 23]. https://www.paho.org/en/topics/tuberculosis . World Health Organization. Global tuberculosis report 2023 [Internet]. Geneva; 2023 [cited 2023 Dec 22]. https://iris.who.int/ . Espinal MA, Báez J, Soriano G, Garcia V, Laszlo A, Reingold AL, et al. 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ShORRT (Short, all-Oral Regimens for Rifampicin-resistant Tuberculosis) Research Package Protocol [Internet]. 2020 [cited 2024 Jan 28]. https://tdr.who.int/docs/librariesprovider10/shorrt-initiative/shorrt-generic-protocol-june2020_en.pdf?sfvrsn=df85f6c1_3 . Nguyen TMP, Le THM, Merle CSC, Pedrazzoli D, Nguyen NL, Decroo T, et al. Effectiveness and safety of bedaquiline-based, modified all-oral 9–11-month treatment regimen for rifampicin-resistant tuberculosis in Vietnam. Int J Infect Dis. 2023;126:148–54. Zhdanova E, Goncharova O, Davtyan H, Alaverdyan S, Sargsyan A, Harries AD, et al. 9–12 months short treatment for patients with MDR-TB increases treatment success in Kyrgyzstan. J Infect Dev Ctries. 2021;15(91):S66–74. Trubnikov A, Hovhannesyan A, Akopyan K, Ciobanu A, Sadirova D, Kalandarova L et al. Effectiveness and safety of a shorter treatment regimen in a setting with a high burden of multidrug-resistant tuberculosis. Int J Environ Res Public Health. 2021;18(8). Lecai J, Mijiti P, Chuangyue H, Qian G, Weiguo T, Jihong C. Treatment outcomes of multidrug-resistant tuberculosis patients receiving ambulatory treatment in Shenzhen, China: a retrospective cohort study. Front Public Health. 2023;11. Borisov S, Danila E, Maryandyshev A, Dalcolmo M, Miliauskas S, Kuksa L et al. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report. Eur Respir J [Internet]. 2019 Dec 1 [cited 2024 Mar 1];54(6). https://pubmed.ncbi.nlm.nih.gov/31601711/ . Sotgiu G, Pontali E, Migliori GB. Linezolid to treat MDR-/XDR-tuberculosis: Available evidence and future scenarios. European Respiratory Journal. Volume 45. European Respiratory Society; 2015. pp. 25–9. Mase A, Lowenthal P, True L, Henry L, Barry P, Flood J. Low-Dose Linezolid for Treatment of Patients With Multidrug-Resistant Tuberculosis. Open Forum Infect Dis. 2022;9(12). Tables Table 1 . Demographic and Clinical Characteristics of Patients with RR/MDR-TB included in mSTR cohort in Dominican Republic Characteristics Total (N=113) Gender n (%) Male 80(71%) Female 33(29%) Age in years n (%) mean (SD) 40(15) 15-24 16(14%) 25-55 74(65%) >55 23(21%) Type of patient 1 n (%) New case 85(75%) Relapse 16 (14 %) Treatment after LFTU 2 6 (5%) Treatment after failure 3(3%) Other treatment 3(3%) Disease site n (%) Pulmonary 113(100%) Tuberculosis treatment history n (%) Previously treated with only first-line drugs 3 26(23%) Co-morbidities n (%) HIV positive 14 (12.39%) Hepatitis C positive 1 (0.88%) Diabetes positive 18 (15.93%) Existing neuropathy 7(6.19%) Bacteriological characteristics n (%) Positive sputum culture 75 (66%) Rifampicin resistant 112(98%) Isoniazid resistant 67 (59%) Fluoroquinolone sensitive 4 72(63.72%) Fluoroquinolone sensitivity Unknown 41 (36.28%) Chest X-Ray n (%) Cavity 71 (63%) Extend of the disease n (%) A (<25%) 41(36%) B (25-49%) 43 (38%) C (≥ 50%) 25(22%) Laboratory and Clinical Parameters median (Q1-Q3) 5 Haematological evaluation Haemoglobin (g/dL) 11.8 (10.4-13.2) Platelet (10 9 /L) 396 (291- 470) White blood count (10 9 /L) 9.02(6.8-11.8) Liver and renal function AST/SGOT (U/L) 24 (17-36) Creatinine (mg/dL) 0.83 (0.7-1) Clinical evaluation BMI in kg/m² 20.25 (17.95-23.2) QTcF Intervals (ms) 396 (355-437) Health Quality of life (EQ-5D) n (%) Mobility Slight/moderate problems 14(16%) Severe problems / Unable 2(2%) Self-care Slight/moderate problems 4(5%) Severe problems / Unable 1(1%) Usual activities Slight/moderate problems 15(17%) Severe problems / Unable 2(2%) Pain/Discomfort Slight/moderate problems 14(16%) Severe problems / Unable Anxiety/Depression Slight/moderate problems 1(1%) Severe problems / Unable 15(17%) General health assessment (EQ-VAS score) Mean (SD) 79 (14) 1 Definitions based on the recommendations of the World Health Organization (WHO)[9] 2 LFTU: Lost to follow-up. 3 Two previously treated cases missing information. 4 Take the information from LPA. If it is missing, then take the information from DST. 5 Q1 = 1 st quartile; Q3 = 3 rd quartile Table 2 . Treatment Outcomes after six months follow up for patients undergoing mSTR Treatment outcome 1 Total (n=113) n (%) Favorable 2 89 (79%) Unfavorable 24 (21%) Died during the treatment 7 (6%) Lost to follow up 16 (14%) Treatment failed 3 1 (1%) Relapse at 6 months follow up 0 (0 %) 1 Definitions of TB treatment outcomes for Patients with RR/MDR-TB based on the recommendations of the World Health Organization (WHO)[9] . 2 Favorable include successfully treated without recurrence 6 months after the end of the treatment. 3 Permanent change of at least 2 drugs because of Adverse Drug Reactions (ADR) Table 3 . Adverse events and grading in patients undergoing mSTR. Adverse Events Total of patient (n=113) n % Serious Adverse Events Had at least one serious adverse event 14 12 Type of SAE Total of events (n= 15) Death 7 47 Life-threatening experience 2 13 Hospitalization/prolongation of hospitalization 2 13 Persistently/significantly disabling events 0 0 Congenital anomalies/birth defects 0 0 Other medically important events 4 27 SAE related to use of medications Total of patients (n= 15) Related 6 40 Not related 7 47 Insufficient data to assess 2 13 Adverse of interest Had at least one adverse event 93 82 Type of AE of interest and their grading 1 Total of event (n=237) Anemia 41 17 Grade 1 24 59 Grade 2 9 22 Grade 3 7 17 Grade 4 1 2 Thrombopenia 11 5 Grade 1 7 64 Grade 2 3 27 Grade 3 1 9 Leukopenia 3 1 Grade 1 2 100 Elevated liver enzymes 56 23 Grade 1 47 84 Grade 2 8 14 Grade 4 1 2 Prolonged QtcF 119 50 Grade 1 22 19 Grade 2 78 65 Grade 3 19 16 Peripheral neuropathy 6 3 Grade 1 3 50 Grade 2 3 50 Anxiety 2 1 Grade 1 1 50 Grade 2 1 50 Optic neuritis 0 0 Proportion of patients who experienced each AE of interest Total of patient (n=113) Anemia 30 27 Thrombopenia 8 7 Leukopenia 1 1 Elevated liver enzymes 41 36 Prolonged QtcF 2 77 68 Peripheral neuropathy 6 5 Anxiety 2 2 Optic neuritis 0 0 Number of episodes of AE of interest per patient Total of patient (n=93) Mean (SD) 3 (2) Median (IQR) 2 (1, 3) Minimum 1 Maximum 8 1 The severity of adverse events was graded according to the Division of AIDS table for grading the severity of adult and pediatric patients, as outlined by the U.S. National Institutes of Health[14] 10 . 2 The analysis of QTc prolongation utilized the National Cancer Institute Common Terminology of Clinical Adverse Events (CTCAE) v5.013 Table 4 . Health related quality of life evaluation among patients undergoing evaluation. HQoL evaluation Baseline - 4 month Baseline - End of treatment , EQ-5D-5L Mobility Any problem - No change 1 (9.1%) 0 (0%) Better 8 (72.7%) 8 (100%) Worse 2 (18.2%) 0 (0%) Self-care Any problem - No change 0 (0%) 0 (0%) Better 2 (50.0%) 1 (50.0%) Worse 2 (50.0%) 1 (50.0%) Usual Activities Any problem - No change 1 (7.7%) 0 (0%) Better 9 (69.2%) 10 (100%) Worse 3 (23.1%) 0 (0%) Pain / Discomfort Any problem - No change 1 (7.1%) 0 (0%) Better 10 (71.4%) 10 (90.9%) Worse 3 (21.4%) 1 (9.1%) Anxiety/Depression Any problem - No change 0 (0%) 0 (0%) Better 12 (92.3%) 10 (90.9%) Worse 1 (7.7%) 1 (9.1%) EQ-VAS score Mean difference (SD) 3.3 (9.0) 15.5 (14.0) Additional Declarations No competing interests reported. Supplementary Files SupplementaryDataS1S2.docx Cite Share Download PDF Status: Published Journal Publication published 09 Feb, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 19 Apr, 2024 Editor assigned by journal 18 Apr, 2024 Submission checks completed at journal 18 Apr, 2024 First submitted to journal 15 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4271608","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":293173908,"identity":"49b2ce90-afe7-4193-9533-5d21a4d98b2d","order_by":0,"name":"María 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19:23:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4271608/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4271608/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-10417-w","type":"published","date":"2025-02-09T15:57:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55511649,"identity":"fa7ed67c-b6ae-43fa-a8c3-b10c2c21f0fb","added_by":"auto","created_at":"2024-04-29 12:37:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103933,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of eligible study participants from RR/MDR-TB notified patients in 2022.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4271608/v1/f6bd9c0959f4282715f31e0e.png"},{"id":55511647,"identity":"fa6b8fa8-a3ad-42b7-bf81-09fc2c48d57e","added_by":"auto","created_at":"2024-04-29 12:37:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":23731,"visible":true,"origin":"","legend":"\u003cp\u003eTime to Culture Conversion in patients undergoing mSTR for RR/MDR-TB.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4271608/v1/ce728a67952ae05d92af5bed.png"},{"id":75929975,"identity":"66ed46ff-c38e-4502-a879-075f1a48f1ab","added_by":"auto","created_at":"2025-02-10 16:08:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1614267,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4271608/v1/c015bf76-45e0-4768-a764-acef857dbaa1.pdf"},{"id":55511648,"identity":"63587650-44e3-46de-b3ca-89cf3d3fc9f4","added_by":"auto","created_at":"2024-04-29 12:37:46","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":36460,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryDataS1S2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4271608/v1/c81faa2bb03575780e66f799.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of a Modified Short all oral Treatment Regimen for Rifampicin-Multidrug Resistant Tuberculosis in Dominican Republic","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eTuberculosis (TB), one of the most prevalent infectious diseases globally, continues to exert a significant burden on mortality and morbidity. In 2022 TB ranked as the second- largest infectious killer worldwide, surpassed only by coronavirus disease (COVID-19). It was reported as the primary cause of death among people with the human immunodeficiency virus (HIV) and a significant contributor to deaths related to antimicrobial resistance[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In 2022, the global estimate for cases of multidrug resistant or rifampicin-resistant TB (RR/MDR-TB) was 410,000. In the Region of the Americas, approximately 12,000 cases of RR/MDR-TB were estimated, constituting an estimated proportion of 3.2% (2.1\u0026ndash;4.4) of new cases, with 5,444 cases reported [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Dominican Republic has consistently ranked among the top five countries with the highest MDR-TB rate in the Region of the Americas since the publication of the first national surveillance report in 1998 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. With a drug susceptibility testing (DST) coverage of 89% and an estimated proportion of 6.8% (6-7.7) among new cases, the Dominican Republic reported 185 cases RR/MDR-TB out of 4,306 notified in 2022 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBetween 2006 and 2008, cohorts on standardized regimens achieved a success rate of 74% at national level [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These regimens covered periods of 18\u0026ndash;24 months, with injectable drugs administered for six months. From 2014, the decentralization process and an outpatient model of care for RR/MDR-TB was introduced, maintaining regimens with injectables. However, there was a decline in treatment success from 74\u0026ndash;60%, mainly attributed to high rates of patients lost to follow-up (28\u0026ndash;35%). Following the World Health Organization (WHO) recommendation of an all-oral treatment regimen[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], the success rate increased from 60\u0026ndash;75% in 2020. This was due to a decrease of the lost to follow-up rate to 18% by 2020. Nevertheless, additional measures needed to be taken to further decrease the percentage of patients lost to follow-up and improve overall success rate for all patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Shortening the length of the treatment was felt as a key strategy to consider.\u003c/p\u003e \u003cp\u003eSince 2020, the national TB control program (NTCP) of the Dominican Republic, in collaboration with the Special Programme for Research and Training in Tropical Diseases (TDR) of the World Health Organization (WHO) and the Pan American Health Organization (PAHO), has been conducting operational research on the effectiveness, safety, and impact on health-related quality of life (HQoL) of RR/MDR-TB patients treated with the modified Short all oral Treatment Regimen (mSTR) for drug-resistant TB patients[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].The introduction of a fully oral modified short treatment regimen holds significant potential to reduce the duration of treatment, enhance treatment compliance, and ultimately increase the success rate of treatment[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe five-drug WHO-recommended STR has been in implementation since February 2022[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Our objective was to evaluate the effectiveness, safety, and impact on HQoL of this 9 to 12 month fully oral shortened RR/MDR-TB under programmatic conditions. In this paper, we present end-of-treatment and follow up outcomes at three and six months after the end of the treatment. This study also aimed to guide RR/MDR-TB treatment policy for Dominican Republic.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy design.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA prospective cohort study was conducted that enrolled patients with RR/MDR-TB between January and December 2022 in seven drug-resistant TB units in the Dominican Republic[2]. The research protocol and data collection tools were developed using the Short all-Oral Regimens for Rifampicin-resistant Tuberculosis (ShoRRT) research package proposed by TDR [8], and adapted to the context of the country.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study population comprised of TB patients with evidence of resistance to at least rifampicin (R) detected by the molecular WHO-recommended rapid diagnostic test for TB (mWRD), Xpert\u0026acirc; MTB/RIF Ultra, or conventional (culture-based) drug susceptibility testing (DST). For minors (18 years of age and younger), inclusion criteria involved confirm TB case without DST but close contact with a confirmed RR/MDR-TB case. The total expected number of patients depended on those meeting the specified criteria in the country during 2022. Isoniazid (H) and Fluoroquinolone (FQ) susceptibility were assessed by Line Probe Assay (LPA) and/or phenotypic DST. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main exclusion criteria included FQ resistance, inability to take oral medications, allergies, or the use of medications contraindicated with any of the drugs in the mSTR regimen, and a Fredericia-corrected QT interval (QTcF) of \u0026ge; 500 ms at baseline that does not correct with medical treatment. Additionally, patients less than 2 years of age were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatients who met the inclusion criteria and gave their consent were enrolled in the study as they presented at the health center for treatment during the study period. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy procedures.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eShort treatment regimen under investigation\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study regimen consisted of five drugs: linezolid (Lzd), bedaquiline (Bdq), levofloxacin (Lfx), clofazimine (Cfz), and cycloserine (Cs),\u0026nbsp;at doses calculated by weight according to the recommendation of WHO [9] (\u003cstrong\u003esupplementary table S1\u003c/strong\u003e). The initial phase compromised four-months with Lzd-Bdq-Lfx-Cfz-Cs, followed by a two-month continuation phase with Bdq-Lfx-Cfz-Cs, and a three-month maintenance phase with Lfx-Cfz-Cs. The total treatment duration was 9 months with a possible extension to 12 months if the 4 -month sputum culture was positive. Patient follow-up continued for 12 months (3, 6 and 12 months) after the end of the treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEvaluation criteria\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffectiveness\u003c/strong\u003e: the proportion of RR/MDR-TB patients with a favorable treatment outcome defined as cured or treatment completed without recurrence at 3, 6 and 12 months after the end of the treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety\u003c/strong\u003e: the proportion of\u0026nbsp;RR/MDR-TB\u0026nbsp;patients who experience a serious adverse event up to six-months after the end of the treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHealth-related Quality of Life (HQoL):\u003c/strong\u003e HQoL was evaluated using the Euroquol EQ-5D-5L questionnaire[10], a concise, generic measure of self-reported health status. The assessment focused on determining the proportion of patients who experienced an improvement in their quality of life during the treatment period.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInvestigation plan\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the effectiveness, safety, and impact on the HQoL of the shorter oral treatment regimen implemented in this study, the following parameters were monitored monthly during treatment and six months after the end of the treatment: baseline patient characteristics, clinical evaluation, bacteriology (DST, smear, and culture), laboratory tests (particularly Hemoglobin level), and additional parameters detailed in supplementary \u003cstrong\u003eTable S2\u003c/strong\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData was collected using standardized forms built on the REDCap electronic data capture tool hosted at WHO Geneva[11]. Periodic data cleaning for identifying missing data and inconsistences was performed centrally by the coordinating center of the Dominican Republic national TB programme. Data were collected for the following variables: age in years, gender (male, female), TB treatment history, TB type (pulmonary or extra-pulmonary); TB category (new or previously treated); sputum smear result (smear-positive, smear-negative, smear not done); Mycobacterium tuberculosis culture result (positive, negative, not done); drug susceptibility testing (DST) results if available; treatment start date; sputum culture conversion (Yes, No); date of sputum culture conversion; para-clinical parameters (chest X-ray, electrocardiogram, blood test); final treatment outcome (cured, treatment completed, treatment failed, died, lost to follow up and not evaluated) as defined by WHO[12]; TB recurrence; adverse events and HQoL data. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe occurrence of SAEs and Adverse Events of Special Interest related to the drugs used was monitored and reported monthly in accordance with the recommendations of the WHO[13]. These events included blood-related issues, cardiac concerns (such as QTcF prolongation), hepatic complications (Alanine aminotransferase enzyme increase), nervous system disorders (including optic neuritis, peripheral neuropathy) and mental disorders. The severity of adverse events was graded according to the Division of AIDS table for grading the severity of adult and pediatric patients, as outlined by the U.S. National Institutes of Health[14] and for QTc prolongation, the National Cancer Institute Common Terminology of Clinical Adverse Events v5 was utilized[15].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor HQoL assessment, data were collected at enrolment, four months into treatment, at the end of treatment and 12 months after the end of treatment, using the EQ-5D-5L questionnaire[16]. This questionnaire comprises two parts: the EQ-5D-5L, which includes a descriptive system of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) in five levels. Participants indicated for each dimension whether they have no, mild, moderate, severe, or extreme problems. For each dimension, the proportion of patients with no, mild/moderate and severe/extreme problems was determined at each time point. The second part is the EQ-VAS which captures the respondent\u0026rsquo;s overall assessment of their health on a scale from 0 (worst health) to 100 (best health). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCategorical variables were described using frequencies and percentage, while continuous variables were summarized using means with standard deviation or medians with 1\u003csup\u003est\u003c/sup\u003e and 3\u003csup\u003erd\u003c/sup\u003e quartiles. For HQoL data, data analysis, changes in health states for each dimension were determined at four months into treatment and at the end of treatment, alongside mean EQ-VAS scores at baseline and the average difference EQ-VAS score from baseline. Data analyses were performed using STATA software (version 17).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study received ethical approval from the WHO Research Ethics Review Board (Generic Protocol ID: ERC0003305, 08/06/2020) and the Ethics Committee of the Dr. Hugo Mendoza National Center for Research in Maternal and Child Health (CENISMI, 10/07/21). Written informed consent was obtained for all study participants\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eBetween January to December 2022, a total of 185 patients with RR/MDR-TB were diagnosed using Xpert MTB/RIF Ultra in seven drug resistant TB units. Sixty-two patients were excluded due to being unlocatable or deceased before treatment initiation, prior use of\u0026nbsp;drugs from the regimen\u0026nbsp;or not available at the program, age under two years, absence of LPA results, known FQ-resistance, or the presence of cardiovascular complications with QTcF \u0026gt;500ms. Of the remaining 123 patients, screening and consultation were conducted for potential inclusion in the modified short treatment regimen (mSTR). Seven were further excluded due to FQ-resistance identified with second-line drug susceptibility testing (SL-DST), two never initiated the mSTR and one withdrew consent (\u003cstrong\u003eFigure 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline characteristics of patients\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 113 patients were included in the effectiveness analysis. among these patients, 80 were male (71%), with a median age of 40 years, and 74 patients (65%) were aged between 25-55 years. \u003cstrong\u003eTable 1\u003c/strong\u003e presents the baseline characteristics of these patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients had confirmed pulmonary rifampicin resistant TB. Among them, 85 (75%) were new patients, while 28 (25%) had prior treatment with first-line drugs, including 16 (14%) classified as relapses. Fourteen patients (12%) were tested positive for HIV, 18 (16%) had diabetes and 7 (6%) had existing neuropathy. A positive sputum culture was observed in 75 out of 113 patients (66%), with DST results available for 72(64%), with 67 being resistant to isoniazid (59% MDR-TB). Seventy-two (64%) patients had DST results confirming fluoroquinolone susceptibility. Among all patients, 71 (63%) had TB cavities, and 25 (22%) had extended lesions (\u0026ge; 50%) on chest X-Ray (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe hematological evaluation revealed a median hemoglobin level of 11.8 g/dL (10.4-13.2) g/dL. Twenty-seven (24%) patients had grade 1 or more anemia (less than 10.5 g/dl) at baseline. Liver function test was within the normal range (AST/SGOT 24(17-36) U/L), except for one patient. No initial alteration of renal function was observed (creatinine 0.83 (0.7-1) mg/dl). The mean value of the body mass index (BMI) was 20.25 (17.95-23.2)\u0026nbsp;kg/m\u0026sup2; and the mean value QTcF intervals was 396 (355-437) ms.\u003c/p\u003e\n\u003cp\u003eRegarding HQoL,\u0026nbsp;patients reported problems with physical functioning including mobility (18%), self-care (6%) and usual activity (19%). Additionally, 17% of surveyed patients reported problems with pain/discomfort domain, while anxiety/ depression was reported by 19% of participants. The EQ-VAS score mean was 79 (\u0026plusmn;14),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment outcome\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong 113 patients, 89 (79%) had a favorable outcome, defined as being successfully treated without recurrence six months after the end of the treatment. Sixteen patients (14%) were lost to follow up, with three of them lost before completing three months of treatment, and two of these individuals tested negative in cultures. Seven patients (6%) died, and one experienced treatment failure, resulting from a permanent regimen change due to Adverse Drug Reactions (ADRs) (\u003cstrong\u003eTable 2\u003c/strong\u003e). Of the 41 patients who did not have fluoroquinolones\u0026rsquo; DST results, 34 (83%) had a favorable outcome, three (7%) were lost to follow up and four (10%) died.\u0026nbsp;Among the total patients, 75 had a positive culture at baseline, and 69 had a follow up smear result. Culture conversion in the second month was achieved for 60 patients (87%) (\u003cstrong\u003eFigure 2\u003c/strong\u003e). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA favorable outcome was obtained with a treatment duration of nine months for 82 (92%) patients, 11 months for 5 patients and 12 months for 2 patients. The reasons for extending treatment beyond nine months were a positive sputum smear at four months of treatment in 3 patients and difficulties in compliance in 4 patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse events\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 113 patients, 93 (82%) experienced at least one adverse event (AE) of interest. Fourteen patients (12%) had at least one SAE which resulted in death for seven of them. A total of six SAEs were related to the TB drugs (ADRs). None of the ADRs resulted in death.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 237 AEs of special interest were recorded, with 106 (45%) classified as grade 1, 102 (43%) as grade 2, and 27 (11%) as grade 3. Two (1%) of the AEs were Grade 4. The most frequent AEs of special interest included prolonged QTcF in 119 (50%) cases, elevated transaminases in 56 (23%), anemia in 41 (17%), and thrombopenia in 11 (5%). Peripheral neuropathy was found in 6 patients (3%) and none of the patients suffered from optic neuropathy. More details can be found in the \u003cstrong\u003eTable 3\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHealth related Quality of life (HQoL)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn all five dimensions, most patients who reported problem at baseline and were evaluated after four months of treatment felt better (73% for mobility, 50% for self-care, 69% for usual activities, 71% for pain/discomfort and 92% for anxiety/depression). \u0026nbsp;At the end of treatment, almost all evaluated patients who had reported problem at baseline felt better (100% for the dimensions mobility and usual activities; 91% for the dimensions pain/discomfort and anxiety/depression). In the dimension of self-care, only two patients with problem at baseline were evaluated with one showing improvement and one showing worsening (\u003cstrong\u003eTable 4\u003c/strong\u003e). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding the EQ-VAS score, the mean was, 84 (\u0026plusmn;10.9) at four months of treatment and 96 (\u0026plusmn;4) at the end of treatment. The mean difference in EQ-VAS score compared to baseline measurement was 3.3(\u0026plusmn; 9) at four months and 15.5 (\u0026plusmn;14) at the end of the treatment (Table 4).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e This study represents the first investigation conducted in Dominican Republic (DR) to assess the effectiveness, safety, and impact on the health-related quality of life (HQoL) among RR/MDR-TB patients treated with 9\u0026ndash;12 months short all oral treatment.\u003c/p\u003e \u003cp\u003eThe 5-drug all-oral modified short treatment (mSTR) implemented in this study mirrored the long regimen endorsed by the WHO[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. It demonstrated a high early conversion rate (87% at 2 months) and a notable treatment success rate (79%) among RR/MDR-TB patients. This treatment success rate is comparable to the one achieved with the longer treatment regimen with the seven-drug STR containing injectable agents for the 2020 MDR-TB cohort (75%). Notable, none of the cured patients experienced relapse six months after the end of treatment, indicating sustained treatment cure [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur results align with success rates (ranging from 75 to 90%) reported in other countries for RR/MDR-TB patients treated with all oral mSTR[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Importantly, the treatment success achieved with this simplified mSTR, utilizing Bdq, Lfx and Lzd as core drugs, and Cfz and Cs as companion drugs, appears to provide more favorable outcomes than those found in Central Asia. For instance, In Uzbekistan, a cohort of 95 patients achieved only a 66% success rate using seven-drugs regiment with high dose of H and Mfx as core drug, and without Bdq [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the lack of information on FQ susceptibility in 46 (41%) of the 113 patients, a conversion rate of 87% was achieved at two months. The high conversion and treatment success rate of the mSTR evaluated in this study may be attributed to the potent bactericidal and sterilizing activities of the two main drugs, Bdq and Lfx. Indeed, the use of Lzd has been associated with improved treatment outcomes, as reported by Nguyen in 2023[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite a decrease in the percentage of patient\u0026rsquo;s loss to follow-up in the Dominican Republic compared to previous years, dropping from 18% in 2020 to 14% in this study, there remains a need to strengthen a patient-centered care approach to further improve treatment compliance. Analysis of the baseline and control culture results of patients lost to follow-up indicated a low risk of disease transmission to the community and/or development of bedaquiline resistance. Only one patient's culture status could not be determined. No cases of bacteriological failure were recorded. Treatment modification was necessary for only one patient due to adverse events related to medication use, while seven patients died during treatment from causes unrelated to medication use and comorbidities.\u003c/p\u003e \u003cp\u003eAlthough adverse events (AEs) were common during RR/MDR-TB treatment, most of them were grade 1\u0026ndash;2, consistent with findings from other studies[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The most frequent AE was prolonged QTc interval, reported in 68% of cases, which has been documented in other studies and associated with the use of Bdq and Cfz [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTwelve percent of patients experienced SAEs, with drug-related SAEs observed in 5% of patients. Only one patient required modification in the RR/MDR-TB regimen due to elevated transaminases associated with the use of Bdq and Lzd [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Anemia-related SAE was the most frequent, observed in 5 patients (4%), and was associated with the use of Linezolid (Lzd). It was identified at a lower proportion in this study compared to other studies reported where higher doses of Lzd were used[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This success may be attributed to the doses of Lzd used in this study (600 mg), which have been demonstrated to mitigate the toxicity associated with this drug[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. From a national TB programme perspective, this AE seems to be manageable if carefully monitored.\u003c/p\u003e \u003cp\u003eIn this study, patients started the treatment with favorable overall conditions, including disease extent, clinical parameters and HQoL evaluations. This may be attributed to early diagnosis facilitated by the utilization of more sensitive rapid molecular tests.\u003c/p\u003e \u003cp\u003eThe health-related quality of life EQ-VAS score in patient with RR/MDR-TB increased by an average of 16 points at the end of the treatment compared to baseline, indicating a significant enhancement in patients' quality of life throughout the treatment period.\u003c/p\u003e \u003cp\u003eThese results underscore the high effectiveness of the mSRT used in this study for treating patients with RR/MDR-TB in Dominican Republic. This regimen\u0026rsquo;s success enabled the shortening of the standardized treatment regimen, which originally had a longer duration, and facilitated an assessment of its impact on patient quality of life. The study demonstrated that this regimen does not impose a negative impact and, in fact, enhances treatment compliance.\u003c/p\u003e \u003cp\u003eOne of the primary limitations of this research was the limited availability of fluoroquinolone molecular susceptibility testing. This constraint posed challenges in expanding the patient sample, emphasizing the importance of ensuring comprehensive coverage of this diagnostic test for all individuals with RR/MDR TB.\u003c/p\u003e \u003cp\u003eSafety profile appears manageable in most patients, with few serious adverse events observed, and very few attributed to medication use. Active Drug Safety Monitoring (aDSM) has been implemented in the Dominican Republic since begin of programmatic MDR-TB management; however, this study emphasizes the necessity to systematize and enhance aDSM in the country.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis operational research study facilitated the evaluation and integration of a shortened treatment regimen lasting 9 to 12 months, utilizing the same drugs as the prolonged treatment regimen proposed by the WHO, tailored to the conditions in the Dominican Republic. This allowed for the adjustment of guidelines, providing an alternative approach for managing patients with RR/MDR-TB in the country. Furthermore, the implementation of this regimen resulted in improved patient compliance due to its shorter duration. Since September 2023, this short all oral treatment regimen is now the one recommended for RR/MDR-TB patients in Dominican Republic.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCOVID-19: Coronavirus disease\u003c/p\u003e\n\u003cp\u003eHIV: immunodeficiency virus\u003c/p\u003e\n\u003cp\u003eTB: Tuberculosis\u003c/p\u003e\n\u003cp\u003eMDR-TB: Multidrug-Resistant Tuberculosis\u003c/p\u003e\n\u003cp\u003eRR/MDR-TB: Rifampicin-Resistant/Multidrug-Resistant Tuberculosis\u003c/p\u003e\n\u003cp\u003emSTR: Modified Shortened Treatment Regimen\u003c/p\u003e\n\u003cp\u003eShoRRT: Short all-Oral Regimens for Rifampicin-resistant Tuberculosis\u003c/p\u003e\n\u003cp\u003eLzd: Linezolid\u003c/p\u003e\n\u003cp\u003eBdq: Bedaquiline\u003c/p\u003e\n\u003cp\u003eLfx: Levofloxacin\u003c/p\u003e\n\u003cp\u003eCfz: Clofazimine\u003c/p\u003e\n\u003cp\u003eCs: Cycloserine\u003c/p\u003e\n\u003cp\u003eR: Rifampicin\u003c/p\u003e\n\u003cp\u003eH: Isoniazid\u003c/p\u003e\n\u003cp\u003eFQ: Fluoroquinolone\u003c/p\u003e\n\u003cp\u003eDST: Drug Susceptibility Testing\u003c/p\u003e\n\u003cp\u003emWRD: molecular WHO-recommended Rapid Diagnostic test for TB\u003c/p\u003e\n\u003cp\u003eLPA: Line Probe Assay\u003c/p\u003e\n\u003cp\u003eADRs: Adverse Drug Reactions\u003c/p\u003e\n\u003cp\u003eAEs: Adverse events\u003c/p\u003e\n\u003cp\u003eSAEs: Serious Adverse Events\u003c/p\u003e\n\u003cp\u003eQTcF: Fredericia-corrected QT interval\u003c/p\u003e\n\u003cp\u003eHQoL: health-related quality of life\u003c/p\u003e\n\u003cp\u003eNTCP: National Tuberculosis Control Programme\u003c/p\u003e\n\u003cp\u003eTDR: Special Programme for Research and Training in Tropical Diseases\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWHO: World Health Organization\u003c/p\u003e\n\u003cp\u003ePAHO: Pan American Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study obtained ethical approval from the WHO Research Ethics Review Board and the Ethics Committee of the Dr. Hugo Mendoza National Center for Research in Maternal and Child Health. Informed consent was obtained from each participant or respondent. All methods adhered to relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors and respondents involved in this research have consented to the publication of all paper details, data, tables, and images. These materials will be freely accessible on the internet.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData is available within the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed substantially to the conception, design, analysis, and interpretation of data, and participated in the preparation and review of drafts of this manuscript and gave their final consent to the publication of the final version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTDR, the Special Programme for Research and Training in Tropical Diseases, provided technical assistance and catalytic funding (grant 2021/1188581-0) for the conduct of this study as part of the ShORRT initiative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclaimer\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings and conclusions of this article are the intellectual responsibility of its authors and do not necessarily represent the official position of\u0026nbsp;Special Programme for Research and Training in Tropical Diseases\u0026nbsp;of World health Organization, the Pan American Health Organization, Nacional Health Service, and Ministry of Public Health of Dominican Republic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge Ricardo Elias Melgen (National TB Program), and Orqu\u0026iacute;dea Moreno (National Reference TB Laboratory) of the Ministry of Health; Rudelina de los Santos, and Yaneiry Cuevas (Clinical Management Department), and the staff of the DR-TB Regional Units for taking the time and effort to contribute to this research, especially to Marika P\u0026eacute;rez, Jorge Rodr\u0026iacute;guez y Nadiezhda Ratchel, as well as Esther L\u0026oacute;pez of the National Health Service for his continuous support to this initiative. Our gratitude extends to the participating patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePan American Health Organization. Tuberculosis [Internet]. Pan American Health Organization. 2022 [cited 2023 Dec 23]. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.paho.org/en/topics/tuberculosis\u003c/span\u003e\u003cspan address=\"https://www.paho.org/en/topics/tuberculosis\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. Global tuberculosis report 2023 [Internet]. 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Front Public Health. 2023;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorisov S, Danila E, Maryandyshev A, Dalcolmo M, Miliauskas S, Kuksa L et al. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report. Eur Respir J [Internet]. 2019 Dec 1 [cited 2024 Mar 1];54(6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/31601711/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/31601711/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSotgiu G, Pontali E, Migliori GB. Linezolid to treat MDR-/XDR-tuberculosis: Available evidence and future scenarios. European Respiratory Journal. Volume 45. European Respiratory Society; 2015. pp. 25\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMase A, Lowenthal P, True L, Henry L, Barry P, Flood J. Low-Dose Linezolid for Treatment of Patients With Multidrug-Resistant Tuberculosis. Open Forum Infect Dis. 2022;9(12).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eDemographic and Clinical Characteristics of Patients with RR/MDR-TB included in mSTR cohort in Dominican Republic\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"479\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (N=113)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e80(71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33(29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge in years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003emean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e40(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15-24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25-55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e74(65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23(21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of patient\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNew case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e85(75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRelapse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (14 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTreatment after LFTU\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTreatment after failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3(3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOther treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3(3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDisease site\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePulmonary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e113(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTuberculosis treatment history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePreviously treated with only first-line drugs\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26(23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCo-morbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHIV positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14 (12.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHepatitis C positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (0.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiabetes positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18 (15.93%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eExisting neuropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7(6.19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBacteriological characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePositive sputum culture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e75 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRifampicin resistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e112(98%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIsoniazid resistant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67 (59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFluoroquinolone sensitive\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e72(63.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFluoroquinolone sensitivity Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41 (36.28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eChest X-Ray\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCavity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e71 (63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eExtend of the disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eA (\u0026lt;25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e41(36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eB (25-49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e43 (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eC (\u0026ge; 50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25(22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory and Clinical Parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003emedian (Q1-Q3)\u003c/strong\u003e\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHaematological evaluation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11.8 (10.4-13.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePlatelet (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e396 (291- 470)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWhite blood count (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9.02(6.8-11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver and renal function\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAST/SGOT (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 (17-36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.83 (0.7-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical evaluation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI in kg/m\u0026sup2;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20.25 (17.95-23.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eQTcF Intervals (ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e396 (355-437)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealth Quality of life (EQ-5D)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMobility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSlight/moderate problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14(16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSevere problems / Unable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2(2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSelf-care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSlight/moderate problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4(5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSevere problems / Unable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1(1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUsual activities\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSlight/moderate problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15(17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSevere problems / Unable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2(2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePain/Discomfort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSlight/moderate problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14(16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSevere problems / Unable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAnxiety/Depression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSlight/moderate problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1(1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSevere problems / Unable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15(17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGeneral health assessment (EQ-VAS score)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e79 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDefinitions based on the recommendations of the World Health Organization (WHO)[9]\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eLFTU: Lost to follow-up.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003eTwo previously treated cases missing information.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e4\u003c/sup\u003eTake the information from LPA. If it is missing, then take the information from DST.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e5\u003c/sup\u003eQ1 = 1\u003csup\u003est\u003c/sup\u003e quartile; Q3 = 3\u003csup\u003erd\u003c/sup\u003e quartile\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Treatment Outcomes after six months follow up for patients undergoing mSTR\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment outcome\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"top\"\u003e\n \u003cp\u003eTotal (n=113)\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFavorable\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"top\"\u003e\n \u003cp\u003e89 (79%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnfavorable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"top\"\u003e\n \u003cp\u003e24 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"top\"\u003e\n \u003cp\u003eDied during the treatment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"top\"\u003e\n \u003cp\u003e7 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"top\"\u003e\n \u003cp\u003eLost to follow up\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"top\"\u003e\n \u003cp\u003e16 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment failed\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.92840095465394%\" valign=\"bottom\"\u003e\n \u003cp\u003eRelapse at 6 months follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.071599045346062%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDefinitions of TB treatment outcomes for Patients with RR/MDR-TB based on the recommendations of the World Health Organization (WHO)[9] .\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003eFavorable include successfully treated without recurrence 6 months after the end of the treatment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003ePermanent change of at least 2 drugs because of Adverse Drug Reactions (ADR)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Adverse events and grading in patients undergoing mSTR.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"529\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse Events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal of patient (n=113)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.50920245398773%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerious Adverse Events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHad at least one serious adverse event\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of SAE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal of events (n= 15)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eDeath\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eLife-threatening experience\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eHospitalization/prolongation of hospitalization\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003ePersistently/significantly disabling events\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eCongenital anomalies/birth defects\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eOther medically important events\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSAE related to use of medications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal of patients (n= 15)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eRelated\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eNot related\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eInsufficient data to assess\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse of interest\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHad at least one adverse event\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of AE of interest\u0026nbsp;and their grading\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal of event (n=237)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eAnemia\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e41\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e17\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eThrombopenia\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eLeukopenia\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eElevated liver enzymes\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e56\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eProlonged QtcF\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e119\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e50\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003ePeripheral neuropathy\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eAnxiety\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eOptic neuritis\u003c/strong\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eProportion of patients who experienced each AE of interest\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal of patient (n=113)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eAnemia\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eThrombopenia\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eLeukopenia\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eElevated liver enzymes\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eProlonged QtcF\u003csup\u003e2\u003c/sup\u003e\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003ePeripheral neuropathy\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eAnxiety\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eOptic neuritis\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.476370510396976%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.33648393194707%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of episodes of AE of interest per patient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal of patient (n=93)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eMean (SD)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eMedian (IQR)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2 (1, 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eMinimum\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"69.18714555765595%\" valign=\"top\"\u003e\n \u003cul\u003e\n \u003cli\u003eMaximum\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.812854442344044%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eThe severity of adverse events was graded according to the Division of AIDS table for grading the severity of adult and pediatric patients, as outlined by the U.S. National Institutes of Health[14]\u003csup\u003e10\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eThe analysis of QTc prolongation utilized the National Cancer Institute Common Terminology of Clinical Adverse Events (CTCAE) v5.013\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e.\u0026nbsp;Health related quality of life evaluation\u0026nbsp;among patients undergoing evaluation.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHQoL evaluation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline - 4 month\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline - End of treatment\u003c/strong\u003e,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEQ-5D-5L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMobility\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Any problem - No change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e8 (72.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e8 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Worse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e2 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSelf-care\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Any problem - No change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Worse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eUsual Activities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Any problem - No change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e9 (69.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e10 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Worse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e3 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePain / Discomfort\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Any problem - No change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e10 (71.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e10 (90.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Worse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e3 (21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnxiety/Depression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Any problem - No change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Better\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e12 (92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e10 (90.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Worse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e1 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"NaN%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEQ-VAS score\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"NaN%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"NaN%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.0352733686067%\" valign=\"top\"\u003e\n \u003cp\u003eMean difference (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e3.3 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.98236331569665%\" valign=\"top\"\u003e\n \u003cp\u003e15.5 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\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":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Tuberculosis, Multidrug-Resistant, bedaquiline, Linezolid, Short all-oral treatment, Treatment Outcome, Safety, Health-Related Quality of Life, Dominican Republic","lastPublishedDoi":"10.21203/rs.3.rs-4271608/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4271608/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aims to evaluate the effectiveness, safety, and impact on health-related quality of life (HQoL) of a fully oral shortened regimen for Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) over 9 to 12 months under programmatic conditions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA prospective cohort study was conducted on an all-oral modified Shortened Treatment Regimen (mSTR) comprising linezolid (Lzd), bedaquiline (Bdq), levofloxacin (Lfx), clofazimine (Cfz), and cycloserine (Cs). Patients with RR/MDR-TB were enrolled between January and December 2022 across seven drug-resistant TB units in the Dominican Republic.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 113 patients were enrolled, with 87% achieving culture conversion at two months. Treatment outcomes revealed that 79% of patients were successfully treated and didn\u0026rsquo;t relapse six months after the end of the treatment, 14% were lost to follow-up during the treatment, 6% deceased, and one experienced treatment failure due to Adverse Drug Reactions (ADRs). Adverse events (AEs) were common, with 82% of patients experiencing at least one AE with high proportion of QT interval prolongation, elevated transaminases, and anemia. A total of 12% of the patients experiencing Serious Adverse Events (SAEs). Improvement in HQoL dimensions was noted throughout treatment, with the EQ-VAS score increasing by an average of 15.5 by treatment end.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe high treatment success rate of the 5-drug mSTR facilitated the adaptation and integration of a shortened treatment regimen lasting 9 to 12 months in routine care in Dominican Republic. Although AEs were frequent, they were manageable in most cases. Continuous monitoring, especially regarding Lzd and Bdq use, is crucial to effectively mitigate risks. Since September 2023, this short all oral treatment regimen is now the one recommended for RR/MDR-TB patients in Dominican Republic.\u003c/p\u003e","manuscriptTitle":"Evaluation of a Modified Short all oral Treatment Regimen for Rifampicin-Multidrug Resistant Tuberculosis in Dominican Republic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-29 12:37:41","doi":"10.21203/rs.3.rs-4271608/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-19T12:34:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-19T01:31:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-19T01:31:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-04-15T19:21:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"761c74c0-2531-4dfb-ab55-6d4841d55919","owner":[],"postedDate":"April 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T15:59:32+00:00","versionOfRecord":{"articleIdentity":"rs-4271608","link":"https://doi.org/10.1186/s12879-024-10417-w","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-02-09 15:57:03","publishedOnDateReadable":"February 9th, 2025"},"versionCreatedAt":"2024-04-29 12:37:41","video":"","vorDoi":"10.1186/s12879-024-10417-w","vorDoiUrl":"https://doi.org/10.1186/s12879-024-10417-w","workflowStages":[]},"version":"v1","identity":"rs-4271608","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4271608","identity":"rs-4271608","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}