Longitudinal Hepatic and Metabolic Trajectories Following Dolutegravir Initiation in Antiretroviral Therapy (ART)-Naïve People Living With HIV: A Prospective Cohort Study From South India.

Background Dolutegravir (DTG)-based combination antiretroviral therapy (cART), specifically the tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) regimen, is being widely prescribed for the management of people living with HIV (PLHIV) in India and other low- and middle-income countries. Although DTG is well-tolerated, concerns persist regarding its hepatic and metabolic safety. Prospective real-world data characterizing the longitudinal hepatic and metabolic trajectories following DTG initiation in antiretroviral therapy (ART)-naïve South Asian PLHIV remain limited. Therefore, we conducted a prospective study to determine the incidence and grading of liver enzyme elevation (LEE) and characterize the longitudinal trajectories of alanine aminotransferase (ALT), anthropometric, and glycemic parameters over six months in ART-naïve PLHIV initiated on the TLD regimen. Methodology We conducted a six-month prospective cohort study and followed 101 ART-naïve adult PLHIV initiated on the TLD regimen at a tertiary care hospital in Bengaluru, India. Serum ALT, weight, body mass index (BMI), waist circumference, and random blood sugar (RBS) were measured at baseline and at one, two, three, and six months. Repeated-measures analysis of variance (rmANOVA) was used to assess longitudinal trends; paired-samples t-test compared baseline and six-month values for waist circumference; chi-square tests examined categorical associations. Results All 101 enrolled participants completed the six-month follow-up. The mean age was 36.5 ± 11.2 years, and 67 (66.3%) participants were male. Any-grade LEE occurred in 22 (21.8%) participants. Mean ALT rose transiently from 26 ± 14 IU/L at baseline to a peak of 32 IU/L at one month, then declined progressively to 27 ± 17 IU/L at six months; the overall trajectory was not statistically significant (F(1.94, 192.29) = 1.114, P = 0.329). All participants with LEE remained asymptomatic; no jaundice, coagulopathy, or hepatic encephalopathy was observed in this cohort. Statistically significant increases were noted in weight +1.79 kg (F(2.02, 201.87) = 12.549, P < 0.001), and mean BMI +0.71 kg/m² (F(2.00, 199.90) = 13.117, P < 0.001). Mean RBS rose by only +1.06 mg/dL (F(3.71, 370.96) = 2.274, P = 0.066) and waist circumference by +0.17 cm (t(100) = 1.42, P = 0.159) - neither change reached statistical significance. LEE was not significantly associated with age (t(99) = 0.298, P = 0.766), sex (χ²(1) = 3.02, P = 0.082, φ = 0.17), concurrent anti-tuberculosis therapy (Fisher's exact P = 0.116), or alcohol use (χ²(1) = 0.001, P = 0.973, φ = 0.003). Conclusions In ART-naïve South Indian PLHIV initiating DTG-based cART, LEEs were relatively common but were predominantly mild, asymptomatic, and self-limited. LEE was characterized by an early rise in ALT followed by a spontaneous decline in most cases by six months despite uninterrupted therapy, a pattern that may reflect hepatic adaptation. In contrast, body weight and BMI increased progressively throughout follow-up, suggesting that hepatic and metabolic responses to DTG may follow distinct trajectories. Overall, ALT elevations were predominantly mild and self-limited, indicating favorable hepatic tolerability of DTG-based cART in this cohort while highlighting the need for continued metabolic monitoring.