Randomized Trial of Metformin With Anti-Tuberculosis Drugs for Early Sputum Conversion in Adults With Pulmonary Tuberculosis.

BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).

High Prevalence of Lipid Abnormalities and Insulin Resistance Among Antiretroviral Naïve HIV-infected Children in India.

BACKGROUND: As large numbers of children are accessing antiretroviral therapy (ART) in India, we evaluated the dietary intake, growth pattern and risk of metabolic complications like dyslipidemia and insulin resistance among ART-naïve HIV-infected children (CLHIV). METHODS: CLHIV 2-12 years of age, at the time of initiating ART in Chennai and Bangalore, were assessed for their dietary intake, anthropometry, blood CD4 cell count, HIV-1 viral load, fasting serum lipids, glucose and insulin. Homeostatic model assessment-insulin resistance was derived. RESULTS: Three hundred and ninety CLHIV (mean age [SD]: 8 [3] yrs; median viral load: 141,000 [25,876-436,000] copies/mL) were started on non-nucleoside reverse transcriptase inhibitor-based ART. Perinatal infection was documented among 97%. Sixty percent of children were in stage 3 or 4 of World Health Organization clinical staging of HIV/AIDS. Food insecurity was seen in 40% of households. A total of 204 children (52.4%) were stunted and 224 (57.6%) were underweight. Stunting seemed to be more prevalent with increasing age (0-4 years: 48%; >9 years: 60%). Mean intakes of calories, iron, folate and calcium were significantly less than recommended dietary allowances across all age groups. Dyslipidemia, in terms of any abnormal triglycerides or total cholesterol or low-density lipoprotein cholesterol (excluding high-density lipoprotein cholesterol), was seen in approximately 40% of children; insulin resistance in 17%; and C-reactive protein in risk range of metabolic syndrome in 24% of children. CONCLUSIONS: In the background of high food insecurity and malnutrition, cardiometabolic abnormalities were seen in 20%-35% of ART-naïve CLHIV in India emphasizing close monitoring of these children for long-term cardiovascular morbidities after initiation of ART.