Nikhil Gupte

: Infection of HIV is associated with an increased diabetes risk, which also increases tuberculosis risk. It is unknown if similar associations exist with gestational diabetes (GDM). We screened pregnant women living with and without HIV for GDM using oral glucose tolerance testing. In a subgroup of women with latent tuberculosis (positive interferon-gamma [IFN-γ] release assay), we used supernatants from tuberculosis antigen tubes to compare cytokine levels from women with and without GDM, matched by age and HIV status. Of 234 women, 21 (9%) had GDM, 13.9% living with HIV, and 6.5% without HIV (P = 0.06). Compared with women without GDM, women with GDM had lower median IFN-γ (19.1 versus 141.9 pg/mL, P = 0.03) and interleukin-2 (18.7 versus 249 pg/mL, P < 0.01). Our study suggests that HIV infection is associated with an increased risk of GDM, which is associated with decreased Mycobacterium tuberculosis immune responses. Gestational diabetes screening should be prioritized in tuberculosis-endemic countries, especially in women living with HIV.

Background: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. Methods: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. Results: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86–5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01–2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02–1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13–2.07, p = 0.006) and CD4+ counts < 350 cells/mm³ (aSHR = 3.06 vs CD4 > 350 cells/mm³, 95%CI 1.58–5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. Conclusion: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.

Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17–1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26–0.87). Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

India has among the highest rates of infant malnutrition. Few studies investigating the growth patterns of HIV-exposed infants in India or the impact of timing of HIV infection on growth in settings such as India exist.

HIV-infected and HIV-exposed, uninfected infants experience a high burden of infectious morbidity and mortality. Hospitalization is an important metric for morbidity and is associated with high mortality, yet, little is known about rates and causes of hospitalization among these infants in the first 12 months of life.

Distance learning may be useful for building health research capacity. However, evidence that it can improve knowledge and skills in health research, particularly in resource-poor settings, is limited. We compared the impact and acceptability of teaching two distinct content areas, Biostatistics and Research Ethics, through either on-line distance learning format or traditional on-site training, in a randomized study in India. Our objective was to determine whether on-line courses in Biostatistics and Research Ethics could achieve similar improvements in knowledge, as traditional on-site, classroom-based courses. Subjects: Volunteer Indian scientists were randomly assigned to one of two arms. Intervention: Students in Arm 1 attended a 3.5-day on-site course in Biostatistics and completed a 3.5-week on-line course in Research Ethics. Students in Arm 2 attended a 3.5-week on-line course in Biostatistics and 3.5-day on-site course in Research Ethics. For the two course formats, learning objectives, course contents and knowledge tests were identical. Main Outcome Measures: Improvement in knowledge immediately and 3-months after course completion, compared to baseline. Baseline characteristics were similar in both arms (n = 29 each). Median knowledge score for Biostatistics increased from a baseline of 49% to 64% (p < 0.001) 3 months after the on-site course, and from 48% to 63% (p = 0.009) after the on-line course. For the on-site Research Ethics course, median score increased from 69% to 83% (p = 0.005), and for the on-line Research Ethics course from 62% to 80% (p < 0.001). Three months after the course, median gains in knowledge scores remained similar for the on-site and on-line platforms for both Biostatistics (16% vs. 12%; p = 0.59) and Research Ethics (17% vs. 13%; p = 0.14). On-line and on-site training formats led to marked and similar improvements of knowledge in Biostatistics and Research Ethics. This, combined with logistical and cost advantages of on-line training, may make on-line courses particularly useful for expanding health research capacity in resource-limited settings.