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Background: Tuberculosis (TB) remains a major plague of humanity. People with TB (PWTB) are commonly anemic. Here, we assessed whether the severity of anemia in PWTB prior to anti-TB treatment (ATT) was a risk factor for an unfavorable outcome., Methods: Patients ≥ 18 years old with culture-confirmed drug-susceptible pulmonary TB enrolled between 2015 and 2019 in a multi-center Brazilian cohort were followed for up to 24 months and classified according to anemia severity (mild, moderate, and severe), based on hemoglobin levels. A multinomial logistic regression model was employed to assess whether anemia was associated with unfavorable outcome (death, failure, loss to follow-up, regimen modification or relapse), compared to treatment success (cure or treatment completion)., Results: Among 786 participants who met inclusion criteria, 441 (56 %) were anemic at baseline. Patients with moderate/severe anemia were more HIV-seropositive, as well as more symptomatic and had higher frequencies of unfavorable outcomes compared to the other groups. Moderate/severe anemia (adjusted OR [aOR]: 7.80, 95 %CI:1.34-45.4, p = 0.022) was associated with death independent of sex, age, BMI, HIV and glycemic status., Conclusion: Moderate/severe anemia prior to ATT was a significant risk factor for death. Such patients should be closely monitored given the high risk of unfavorable ATT outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Anemia frequently affects people living with HIV (PLHIV). Nevertheless, the impact of anemia on treatment outcomes of patients with HIV-associated tuberculosis (TB) and the underlying molecular profiles are not fully characterized. The aim of this study was to investigate the interplay between anemia, the systemic inflammatory profile, dissemination of TB and death in HIV-TB patients in an ad hoc analysis of results from a prospective cohort study., Methods: 496 hospitalized PLHIV ≥18 years old, with CD4 count <350 cells/μL and high clinical suspicion of new TB infection were enrolled in Cape Town between 2014-2016. Patients were classified according to anemia severity in non-anemic, mild, moderate, or severe anemia. Clinical, microbiologic, and immunologic data were collected at baseline. Hierarchical cluster analysis, degree of inflammatory perturbation, survival curves and C-statistics analyses were performed., Results: Through the analysis of several clinical and laboratory parameters, we observed that those with severe anemia exhibited greater systemic inflammation, characterized by high concentrations of IL-8, IL-1RA and IL-6. Furthermore, severe anemia was associated with a higher Mtb dissemination score and a higher risk of death, particularly within 7 days of admission. Most of the patients who died had severe anemia and had a more pronounced systemic inflammatory profile., Discussion: Therefore, the results presented here reveal that severe anemia is associated with greater TB dissemination and increased risk of death in PLHIV. Early identification of such patients through measurement of Hb levels may drive closer monitoring to reduce mortality. Future investigations are warranted to test whether early interventions impact survival of this vulnerable population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Araújo-Pereira, Schutz, Barreto-Duarte, Barr, Villalva-Serra, Vinhaes, Ward, Meintjes and Andrade.)

Background: Adverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on ATT outcomes., Methods: A prospective cohort study of persons with tuberculosis (TB) at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. Baseline information: race, sex, schooling, economic status, tobacco, drugs and alcohol abuse, HIV-infection status and comorbidities were captured during TB screening and diagnosis. Laboratory exams were performed to confirm TB diagnosis and monitor ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate the probability of ADR-free time. A logistic regression analysis (backward elimination) was performed to identify independent associations with unfavorable outcomes., Results: 550 patients were enrolled, 35.1% were people living with HIV (PLHIV) and ADR occurred in 78.6% of all participants. Smoking (OR: 2.32; 95% CI:1.34-3.99) and illicit-drug use (OR:2.02; 95% CI:1.15-3.55) were independent risk factors for unfavorable outcomes. In PLHIV, alcohol abuse and previous ART use were associated with unfavorable outcomes. In contrast, ADR increased the odds of favorable outcomes in the overall population. PLHIV more frequently experienced grade 3/4-ADR (18.36%), especially "liver and biliary system disorders". Lower CD4 counts (<100 cells/uL) were associated with hepatotoxicity (p = 0.03). ART-naïve participants presented a higher incidence of ADR in comparison with ART-experienced patients., Conclusion: Substance use was associated with unfavorable outcomes, highlighting the need for better strategies to reduce this habit. In contrast, ADRs were associated with favorable outcomes. Attention to the occurrence of ADR in PLHIV is essential, especially regarding hepatotoxicity in those with high immunosuppression., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sant´Anna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: After initiating antiretroviral therapy (ART), approximately 25% of people with HIV (PWH) may develop Immune Reconstitution Inflammatory Syndrome (IRIS), which is associated with increased morbidity and mortality. Several reports have demonstrated that low haemoglobin (Hb) levels are a risk factor for IRIS. To what extent the severity of anaemia contributes to the risk of IRIS and/or death is still insufficiently explored., Methods: We investigated both the presence and severity of anaemia in PWH in a multinational cohort of ART-na..ve patients. A large panel of plasma biomarkers was measured pre-ART and patients were followed up for 6 months. IRIS or deaths during this period were considered as outcomes. We performed multidimensional analyses, logistic regression, and survival curves to delineate associations., Findings: Patients with severe anaemia (SA) presented a distinct systemic inflammatory profile, characterized by higher TNF, IL-6, and IL-27 levels. SA was independently associated with IRIS, with a higher risk of both early IRIS onset and death. Among IRIS patients, those with SA had a higher risk of mycobacterial IRIS., Interpretation: PWH with SA display a more pronounced inflammatory profile, with an elevated risk of developing IRIS earlier and a statistically significant higher risk of death., Funding: Intramural Research Program of National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH). Coordena...·o de Aperfei..oamento de Pessoal de N.ível Superior (Finance code: 001) and the Conselho Nacional de Desenvolvimento Cient.ífico e Tecnol..gico (CNPq), Brazil., Competing Interests: Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

People with HIV (PWH) are at increased risk of developing active tuberculosis (TB), and anemia is a common complication in both conditions. Anemia in TB patients has been linked to immune activation, levels of inflammatory biomarkers in blood, and risk for HIV disease progression and death. In this study we show that anemia was associated with a more pronounced inflammatory profile in HIV-TB coinfected persons in a cohort of 159 individuals with advanced HIV disease (CD4 count < 100 cells/µL) recruited as part of a randomized clinical trial (NCT00988780). A panel of plasma biomarkers was assessed on plasma obtained prior to combination antiretroviral therapy (cART) initiation. We performed a series of multidimensional analyses including clinical variables and concentrations of inflammatory biomarkers to profile systemic inflammation of PWH with and without anemia. We observed that TB participants presented with moderately lower levels of hemoglobin than non-TB participants. These participants also presented a higher Degree of Inflammatory Perturbation (DIP) score, related to increased levels of IFN-γ and TNF. The DIP was associated with TB coinfection and anemia before cART initiation. Future mechanistic studies are warranted to assess the determinants of such associations and the implications on treatment outcomes., Competing Interests: JS-M reports grants from BMS, Pfizer, MSD, and Stendhal outside the submitted work. LJM reports grants from Merck and Gene-One. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Araújo-Pereira, Barreto-Duarte, Arriaga, Musselwhite, Vinhaes, Belaunzaran-Zamudio, Rupert, Montaner, Lederman, Sereti, Madero and Andrade.)

Introduction: Tuberculosis (TB) is a common opportunistic infection among people living with HIV. Diagnostic tests such as culture, Xpert-MTB-RIF, and ULTRA have low sensitivity in paucibacillary TB disease; a blood biomarker could improve TB diagnostic capabilities. We assessed soluble factors to identify biomarkers associated with TB among persons with advanced HIV., Methods: A case-control (1:1) study was conducted, with participants from Rio de Janeiro and Manaus, Brazil. People living with HIV presenting with CD4 count ≤100 cells/mm3 were eligible to participate. Cases had culture-confirmed TB (N=15) (positive for Mycobacterium tuberculosis [Mtb]); controls had HIV-infection only (N=15). Study visits included baseline, month 2 and end of TB therapy, during which samples of peripheral blood were obtained. A panel containing 29 biomarkers including cytokines, chemokines and growth factors was utilized to assess candidate biomarkers using Luminex technology in cryopreserved EDTA plasma samples. We used neural network analysis, based on machine learning, to identify biomarkers (single or in combination) that best distinguished cases from controls. Additional multi-dimensional analyses provided detailed profiling of the systemic inflammatory environment in cases and controls., Results: Median CD4 count and HIV-1 RNA load values were similar between groups at all timepoints. Persons with TB had lower body mass index (BMI) (median=19.6, Interquartile Range [IQR]=18.6-22.3) than controls (23.7; IQR: 21.8 = 25.5, p=0.004). TB coinfection was also associated with increased frequency of other comorbidities. The overall profile of plasma cytokines, chemokines and growth factors were distinct between the study groups at all timepoints. Plasma concentrations of IL-15 and IL-10 were on average lower in TB cases than in controls. When used in combination, such markers were able to discriminate between TB cases and controls with the highest degree of accuracy at each study timepoint., Conclusion: Among persons with advanced HIV, plasma concentrations of IL-15 and IL-10 can be used in combination to identify TB disease regardless of time on anti-TB treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Queiroz, Araújo-Pereira, Barreto-Duarte, Gomes-Silva, Costa, Andrade, Miguez-Pinto, Spener-Gomes, Souza, Benjamin, Sant’Anna, Figueiredo, Mave, Salgame, Ellner, Sterling, Cordeiro-dos-Santos, Andrade and Rolla.)

HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals have an increased risk of tuberculosis prior to loss of peripheral CD4 T cells, raising the possibility that HIV co-infection leads to CD4 T cell depletion in lung tissue before it is evident in blood. Here, we use rhesus macaques to study the early effects of simian immunodeficiency virus (SIV) co-infection on pulmonary granulomas. Two weeks after SIV inoculation of Mtb-infected macaques, Mtb-specific CD4 T cells are dramatically depleted from granulomas, before CD4 T cell loss in blood, airways, and lymph nodes, or increases in bacterial loads or radiographic evidence of disease. Spatially, CD4 T cells are preferentially depleted from the granuloma core and cuff relative to B cell-rich regions. Moreover, live imaging of granuloma explants show that intralesional CD4 T cell motility is reduced after SIV co-infection. Thus, granuloma CD4 T cells may be decimated before many co-infected individuals experience the first symptoms of acute HIV infection., Competing Interests: Declaration of interests The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government. The authors declare no competing interests., (Published by Elsevier Inc.)

Background: Biomarkers of unfavourable tuberculosis (TB) treatment outcomes are needed to accelerate new drug and regimen development. Whether plasma cytokine levels can predict unfavourable TB treatment outcomes is unclear., Methods: We identified and internally validated the association between 20 a priori selected plasma inflammatory markers and unfavourable treatment outcomes of failure, recurrence and all-cause mortality among adults with drug-sensitive pulmonary TB in India. We externally validated these findings in two independent cohorts of predominantly diabetic and HIV co-infected TB patients in India and South Africa, respectively., Results: Pre-treatment interferon-γ, interleukin (IL)-13 and IL-6 were associated with treatment failure in the discovery analysis. Internal validation confirmed higher pre-treatment IL-6 concentrations among failure cases compared with controls. External validation among predominantly diabetic TB patients found an association between pre-treatment IL-6 concentrations and subsequent recurrence and death. Similarly, external validation among predominantly HIV co-infected TB patients found an association between pre-treatment IL-6 concentrations and subsequent treatment failure and death. In a pooled analysis of 363 TB cases from the Indian and South African validation cohorts, high pre-treatment IL-6 concentrations were associated with higher risk of failure (adjusted OR (aOR) 2.16, 95% CI 1.08-4.33; p=0.02), recurrence (aOR 5.36, 95% CI 2.48-11.57; p<0.001) and death (aOR 4.62, 95% CI 1.95-10.95; p<0.001). Adding baseline IL-6 to a risk prediction model comprised of low body mass index, high smear grade and cavitation improved model performance by 15% (C-statistic 0.66 versus 0.76; p=0.02)., Conclusions: Pre-treatment IL-6 is a biomarker for unfavourable TB treatment outcomes. Future studies should identify optimal IL-6 concentrations for point-of-care risk prediction., Competing Interests: Conflict of interest: A.N. Gupte has nothing to disclose. Conflict of interest: P. Kumar has nothing to disclose. Conflict of interest: M. Araújo-Pereira has nothing to disclose. Conflict of interest: V. Kulkarni has nothing to disclose. Conflict of interest: M. Paradkar has nothing to disclose. Conflict of interest: N. Pradhan has nothing to disclose. Conflict of interest: P. Menon has nothing to disclose. Conflict of interest: C. Padmapriyadarsini reports funding from the Dept of Biotechnology, Government of India, within the scope of the present manuscript. Conflict of interest: L-E. Hanna has nothing to disclose. Conflict of interest: S.V.B. Yogendra Shivakumar has nothing to disclose. Conflict of interest: N. Rockwood has nothing to disclose. Conflict of interest: E. Du Bruyn has nothing to disclose. Conflict of interest: R. Karyakarte has nothing to disclose. Conflict of interest: S. Gaikwad has nothing to disclose. Conflict of interest: R.C. Bollinger reports research support from the NIH and Ujala Foundation, within the scope of the present manuscript. Conflict of interest: J. Golub reports grants to their institution from the NIH, within the scope of the present manuscript. Conflict of interest: N. Gupte reports grants to their institution from the NIH, within the scope of the present manuscript. Conflict of interest: V. Viswanathan has nothing to disclose. Conflict of interest: R.J. Wilkinson has nothing to disclose. Conflict of interest: V. Mave has nothing to disclose. Conflict of interest: S. Babu has nothing to disclose. Conflict of interest: H. Kornfeld has nothing to disclose. Conflict of interest: B.B. Andrade has nothing to disclose. Conflict of interest: A. Gupta reports grants to their institution from the National Institutes of Health within the scope of the present manuscript; grants to their institution from CRDF outside the scope of the present manuscript; and membership of an NIH/NIAID Advisory Council and the Indo-US Science Technology Forum Board., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a clinical aggravation of TB symptoms observed among a fraction of HIV coinfected patients shortly after the start of antiretroviral therapy (ART). Of note, TB-IRIS is characterized by exacerbated inflammation and tissue damage that occurs in response to the elevated production of CD4 + T cell-derived IFN-γ. Nevertheless, the possible participation of CD8 + T cells in TB-IRIS development remains unclear., Methods: We performed a comprehensive assessment of the composition of CD8 + T cell memory subsets and their association with circulating inflammation-related molecules in TB-HIV coinfected patients initiating ART., Results: We found that TB-IRIS individuals display higher frequencies of Antigen-experienced CD8 + T cells during the onset of IRIS and that the levels of these cells positively correlate with baseline mycobacterial smear grade. TB-IRIS individuals exhibited higher frequencies of effector memory and lower percentages of naïve CD8 + T cells than their Non-IRIS counterparts. In both TB-IRIS and Non-IRIS patients, ART commencement was associated with fewer significant correlations among memory CD8 + T cells and cells from other immune compartments. Networks analysis revealed distinct patterns of correlation between each memory subset with inflammatory cytokines suggesting different dynamics of CD8 + T cell memory subsets reconstitution. TB-IRIS patients displayed lower levels of memory cells positive for CXCR3 (a chemokine receptor that plays a role in trafficking activated CD8 + T cells to the tissues) than Non-IRIS individuals before and after ART. Furthermore, we found that CXCR3 + naïve CD8 + T cells were inversely associated with the risk of TB-IRIS development. On the other hand, we noticed that the frequencies of CXCR3 + effector CD8 + T cells were positively associated with the probability of TB-IRIS development., Conclusion: Our data suggest that TB-IRIS individuals display a distinct profile of memory CD8 + T cell subsets reconstitution after ART initiation. Moreover, our data point to a differential association between the frequencies of CXCR3 + CD8 + T cells and the risk of TB-IRIS development. Collectively, our findings lend insights into the potential role of memory CD8 + T cells in TB-IRIS pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tibúrcio, Narendran, Barreto-Duarte, Queiroz, Araújo-Pereira, Anbalagan, Nayak, Ravichandran, Subramani, Antonelli, Satagopan, Anbalagan, Porter, Sher, Swaminathan, Sereti and Andrade.)

Background: Despite widespread availability of curative therapy, tuberculosis (TB) treatment outcomes remain suboptimal. Clinical prediction models can inform treatment strategies to improve outcomes. Using baseline clinical data, we developed a prediction model for unsuccessful TB treatment outcome and evaluated the incremental value of human immunodeficiency virus (HIV)-related severity and isoniazid acetylator status., Methods: Data originated from the Regional Prospective Observational Research for Tuberculosis Brazil cohort, which enrolled newly diagnosed TB patients in Brazil from 2015 through 2019. This analysis included participants with culture-confirmed, drug-susceptible pulmonary TB who started first-line anti-TB therapy and had ≥12 months of follow-up. The end point was unsuccessful TB treatment: composite of death, treatment failure, regimen switch, incomplete treatment, or not evaluated. Missing predictors were imputed. Predictors were chosen via bootstrapped backward selection. Discrimination and calibration were evaluated with c-statistics and calibration plots, respectively. Bootstrap internal validation estimated overfitting, and a shrinkage factor was applied to improve out-of-sample prediction. Incremental value was evaluated with likelihood ratio-based measures., Results: Of 944 participants, 191 (20%) had unsuccessful treatment outcomes. The final model included 7 baseline predictors: hemoglobin, HIV infection, drug use, diabetes, age, education, and tobacco use. The model demonstrated good discrimination (c-statistic = 0.77; 95% confidence interval, .73-.80) and was well calibrated (optimism-corrected intercept and slope, -0.12 and 0.89, respectively). HIV-related factors and isoniazid acetylation status did not improve prediction of the final model., Conclusions: Using information readily available at treatment initiation, the prediction model performed well in this population. The findings may guide future work to allocate resources or inform targeted interventions for high-risk patients., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: The association of elevated levels of specific inflammatory markers during pregnancy with adverse birth outcomes and infant growth could indicate pathways for potential interventions., Objective: To evaluate whether higher levels of certain inflammatory markers during pregnancy are associated with preterm birth (PTB), low birth weight (LBW), and infant growth deficits., Design, Setting, and Participants: In this cohort study of pregnant women with or without HIV, 218 mother-infant pairs were followed up from pregnancy through 12 months post partum from June 27, 2016, to December 9, 2019. Pregnant women aged 18 to 40 years and between 13 and 34 weeks of gestation who were receiving antenatal care were enrolled in a cohort stratified by HIV status; sampling was based on convenience sampling from women receiving antenatal care at Byramjee Jeejeebhoy Government Medical College., Exposures: Levels of multiple circulating inflammation markers during the third trimester of pregnancy., Main Outcomes and Measures: The primary study outcome was PTB (<37 weeks' gestation). Secondary outcomes were LBW (<2500 g) and repeated measures (delivery; 6 weeks post partum; and 3, 6, and 12 months post partum using multivariable generalized linear models) of infant growth outcomes (length-for-age, weight-for-age, and weight-for-length z scores)., Results: The median age of the 218 women at enrollment was 23 years (IQR, 21-27 years). In multivariable models, higher pregnancy levels of interleukin 17A were associated with increased odds of both PTB (adjusted odds ratio [aOR], 2.62; 95% CI, 1.11-6.17) and LBW (aOR, 1.81; 95% CI, 1.04-3.15). Higher levels of interleukin 1β were associated with increased PTB (aOR, 1.47; 95% CI, 1.15-1.89) and infant growth deficits (lower length-for-age z score: adjusted β = -0.10; 95% CI, -0.18 to -0.01; lower weight-for-age z score: adjusted β = -0.07; 95% CI, -0.14 to 0.001)., Conclusions and Relevance: This study suggests that increased levels of certain systemic inflammatory markers, including interleukin 1β and interleukin 17A, during pregnancy were associated with adverse birth outcomes and infant growth deficits. Future studies should evaluate whether potential interventions to modulate specific inflammatory pathways during pregnancy could improve birth outcomes and infant growth.

Objective: There are limited studies on the association of HIV infection with systemic inflammation during pregnancy., Design: A cohort study (N = 220) of pregnant women with HIV (N = 70) (all on antiretroviral therapy) and without HIV (N = 150) were enrolled from an antenatal clinic in Pune, India., Methods: The following systemic inflammatory markers were measured in plasma samples using immunoassays: soluble CD163 (sCD163), soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), C-reactive protein (CRP), alpha 1-acid glycoprotein (AGP), interferon-β (IFNβ), interferon-γ (IFNγ), interleukin (IL)-1β, IL-6, IL-13, IL-17A, and tumor necrosis factor α (TNFα). Generalized estimating equation (GEE) and linear regression models were used to assess the association of HIV status with each inflammatory marker during pregnancy and by trimester, respectively., Results: Pregnant women with HIV had higher levels of markers for gut barrier dysfunction (I-FABP), monocyte activation (sCD14) and markers of systemic inflammation (IL-6 and TNFα), but surprisingly lower levels of AGP, an acute phase protein, compared with pregnant women without HIV, with some trimester-specific differences., Conclusion: Our data show that women with HIV had higher levels of markers of gut barrier dysfunction, monocyte activation and systemic inflammation. These markers, some of which are associated with preterm birth, might help explain the increase in adverse birth outcomes in women with HIV and could suggest targets for potential interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A new tuberculosis (TB) diagnostic cartridge assay, which detects a 3-gene TB signature in whole blood, was not diagnostic in women with maternal TB disease in India (area under the curve [AUC] = 0.72). In a cohort of pregnant women, we identified a novel gene set for TB diagnosis (AUC = 0.97) and one for TB progression (AUC = 0.96). [ABSTRACT FROM AUTHOR]

Background Despite widespread availability of curative therapy, tuberculosis (TB) treatment outcomes remain suboptimal. Clinical prediction models can inform treatment strategies to improve outcomes. Using baseline clinical data, we developed a prediction model for unsuccessful TB treatment outcome and evaluated the incremental value of human immunodeficiency virus (HIV)–related severity and isoniazid acetylator status. Methods Data originated from the Regional Prospective Observational Research for Tuberculosis Brazil cohort, which enrolled newly diagnosed TB patients in Brazil from 2015 through 2019. This analysis included participants with culture-confirmed, drug-susceptible pulmonary TB who started first-line anti-TB therapy and had ≥12 months of follow-up. The end point was unsuccessful TB treatment: composite of death, treatment failure, regimen switch, incomplete treatment, or not evaluated. Missing predictors were imputed. Predictors were chosen via bootstrapped backward selection. Discrimination and calibration were evaluated with c-statistics and calibration plots, respectively. Bootstrap internal validation estimated overfitting, and a shrinkage factor was applied to improve out-of-sample prediction. Incremental value was evaluated with likelihood ratio–based measures. Results Of 944 participants, 191 (20%) had unsuccessful treatment outcomes. The final model included 7 baseline predictors: hemoglobin, HIV infection, drug use, diabetes, age, education, and tobacco use. The model demonstrated good discrimination (c-statistic = 0.77; 95% confidence interval,.73–.80) and was well calibrated (optimism-corrected intercept and slope, –0.12 and 0.89, respectively). HIV-related factors and isoniazid acetylation status did not improve prediction of the final model. Conclusions Using information readily available at treatment initiation, the prediction model performed well in this population. The findings may guide future work to allocate resources or inform targeted interventions for high-risk patients. [ABSTRACT FROM AUTHOR]