Dolutegravir Is Associated With Lower Odds of Gestational Diabetes Compared to Other Antiretroviral Therapy Regimens Among Pregnant Women in India: A Cross-Sectional Analysis.

INTRODUCTION: In non-pregnant adults living with HIV, dolutegravir is associated with weight gain and increased type 2 diabetes risk. In pregnancy, data on the effect of dolutegravir on gestational diabetes (GDM) risk is inconclusive. Data are particularly limited in Asian populations, where diabetes risk is especially high and not always associated with weight gain. We examined the association of dolutegravir with GDM among women living with HIV in India. METHODS: We combined data from two cohorts of pregnant women living with HIV conducted at BJ Government Medical College in Pune, India-the PRACHITi study (2016-2019) and the PRAGATHi study (2023-present). Women were screened for GDM with the fasting 2-h 75 g oral glucose tolerance test and diagnosed by World Health Organization criteria. Demographics, anthropometrics, antiretroviral therapy (ART), CD4 count and HIV viral load were collected at screening. Multivariate logistic regression was used to determine the association between current dolutegravir use and GDM. RESULTS: Of 254 women living with HIV, 99.2% (n = 252) were on ART, of whom 66.3% (n = 167) were on dolutegravir-, 22.6% (n = 57) were on efavirenz- and 6.3% (n = 16) were on protease inhibitor (PI)-based ART. Overall, median CD4 count was 549.5 cells/mm3 (IQR 401-753), and 82.2% (n = 198) had undetectable viral load. Median body-mass index (BMI) was 21.3 kg/m2 (IQR 19.4-23.8). The prevalence of GDM was 11.8% (N = 30). Among women on dolutegravir-based ART, the prevalence was 10.8% (N = 18); among women on efavirenz-based ART, the prevalence was 12.3% (N = 7), and the prevalence was 25% (N = 4) among women on PI-based ART. Compared to women not taking dolutegravir, women taking dolutegravir had similar age and BMI but greater weight gain from the second to the third trimester (3.7 vs. 2.9 kg, p <0.01) and infant birthweight percentile (14.2 vs. 6.9, p <0.01). On multivariate logistic regression, dolutegravir use was associated with lower odds of GDM than other ART (aOR 0.2, 95% CI 0.1-1.0) irrespective of viral load and time on ART. Older age (aOR 1.1, 95% CI 1.1-1.2) and second-trimester BMI (aOR 1.2 per kg/m2, 95% CI 1.1-1.3) were also associated with GDM. CONCLUSIONS: Women on dolutegravir had lower odds of GDM compared to women taking other ART, despite greater weight gain. Ongoing studies are investigating the possible anti-inflammatory mechanisms.