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Importance The benefit of daily over thrice-weekly antituberculosis therapy among HIV-positive patients with pulmonary tuberculosis (TB) who are receiving antiretroviral therapy remains unproven. Objective To compare the efficacy and safety of daily, part-daily, and intermittent antituberculosis therapy regimens in the treatment of HIV-associated pulmonary TB. Design, Setting, and Participants This open-label, randomized clinical trial was conducted by the National Institute for Research in Tuberculosis, south India. Adults infected with HIV with newly diagnosed, culture-positive, pulmonary TB were enrolled between September 14, 2009, and January 18, 2016. Interventions Patients were randomized to daily, part-daily, and intermittent antituberculosis therapy regimens, stratified by baseline CD4 lymphocyte count and sputum smear grade. Antiretroviral therapy was initiated as per national guidelines. Clinical and sputum microbiological examinations of patients were performed monthly until 18 months after randomization. Adverse events were recorded using standard criteria. Main Outcomes and Measures The primary outcome was favorable response, defined as treatment completion with all available sputum cultures negative forMycobacterium tuberculosisduring the last 2 months of treatment. Unfavorable responses included treatment failures, dropouts, deaths, and toxic effects among regimens. Results Of 331 patients (251 [76%] male; mean [SD] age, 39 [9] years; mean [SD] HIV viral load, 4.9 [1.2] log10copies/mL; and median [interquartile range] CD4 lymphocyte count, 138 [69-248] cells/μL), favorable responses were experienced by 91% (89 of 98), 80% (77 of 96), and 77% (75 of 98) in the daily, part-daily, and intermittent regimens, respectively. With the difference in outcome between daily and intermittent regimens crossing the O’Brien-Fleming group sequential boundaries and acquired rifampicin resistance emergence (n = 4) confined to the intermittent group, the data safety monitoring committee halted the study. A total of 18 patients died and 18 patients dropped out during the treatment period in the 3 regimens. Six, 4, and 6 patients in the daily, part-daily, and intermittent regimens, respectively, had TB recurrence. Conclusions and Relevance Among HIV-positive patients with pulmonary TB receiving antiretroviral therapy, a daily anti-TB regimen proved superior to a thrice-weekly regimen in terms of efficacy and emergence of rifampicin resistance. Trial Registration clinicaltrials.gov Identifier:NCT00933790

Background Antiretroviral therapy (ART) associated dyslipidaemia has been reported among children living with HIV (CLHIV) in both developed and developing countries. Not much data is available on changes in blood lipid profile among CLHIV on first-line ART in India. Aims: To study the changes in the Lipid profile among CLHIVs, 12 months after initiating a non-nucleoside reverse transcriptase inhibitor-based (NNRTI) ART Methods A prospective multicentric study enrolled HIV infected children, between 2-12 years of age, initiating NNRTI-based ART in south India. Clinical details, anthropometry and fasting blood for estimating serum total cholesterol (TC), triglyceride (TGL), high-density cholesterol (HDL-c), low-density cholesterol (LDL-c), plasma viral load and CD4 cell counts was collected. These measurements were repeated at 6th and 12th month after ART initiation. Proportion of children with abnormal lipid profile at baseline and 12 months after ART were compared using McNemar test. Generalized linear model was applied to predict factors associated with changes in serum lipid levels 12 months post-ART. Results Of the 393 HIV-infected children, 66 % received Zidovudine and 14 % Stavudine in their ART regimen. After 12 months of ART, TC, LDL-c and HDL-c increased from baseline by a mean of 31mg/dL, 13.7 mg/dL and 19mg/dl, respectively. TC/HDL-c ratio decreased from a mean of 5.1 to 3.5 (all changes, P 200 mg/dL for 3% and 13% of patients, LDL-c was >130 mg/dL for 5% and 8%, HDL-c was 150 mg/dL for 38% and 24%. Baseline HIV viral load >400 copies/mL (P, 0.01) was associated with increase in HDL-c and lower TG levels (P, 0.008). Baseline CD4 %

BACKGROUND: Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression. OBJECTIVES: To study the influence of age drug dose and formulation type nutritional status and CYP2B6 516G>T polymorphism on blood concentrations of nevirapine in children treated with generic antiretroviral drugs. METHODS: A multicentre study was conducted at four sites in India. HIV-infected children receiving generic nevirapine-based fixed-dose combinations were recruited. Trough and 2 h nevirapine plasma concentrations were determined by HPLC. Characterization of the CYP2B6 gene polymorphism was performed using direct sequencing. Clinical and nutritional status was recorded. Groups were compared using the Mann-Whitney U-test and multivariable logistic regression analysis was performed to identify factors contributing to low drug levels. RESULTS: Ninety-four children of median age 78 months were studied; 60% were undernourished or stunted. Stunted children had a significantly lower 2 h nevirapine concentration compared with non-stunted children (P < 0.05); there were no significant differences in trough concentrations between different nutritional groups. Nevirapine levels were significantly higher in children with TT compared with GG and GT CYP2B6 genotypes (P < 0.01). Children