Dolutegravir-Based Regimen Associated With Greater Weight Gain in Treatment-Naive Individuals

Weight gain associated with antiretroviral therapy (ART), specifically integrase strand transfer inhibitor (INSTI)-based regimens, has been a focus of recent studies, some of which have identified a link between switching to INSTI regimens and metabolic changes in virologically suppressed people living with HIV (PLWH).

In a new study published in Clinical Infectious Diseases, investigators with Vanderbilt University Medical Center sought to evaluate whether treatment-naive PLWH experienced a similar weight gain when initiating dolutegravir-based ART compared with other ART regimens.

A total of 1152 adult treatment-naïve PLWH in the Vanderbilt Comprehensive Care Clinic cohort initiated either an INSTI regimen or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART between January 2007 and June 2016. Among them, 356 began INSTI-based ART (135 dolutegravir, 157 elvitegravir, and 64 raltegravir). Eighty six percent of the participant were male, and 49% were white, with a median age of 35 years, a median body mass index (BMI) of 25.1 kg/m², and a media CD4+ T-cell count of 318 cells/mm³.

Between both ART classes, virologic suppression at 18 months was similar, while weight gain was statistically significant among PLWH who initiated the dolutegravir-based regimen. At the 18-month mark, PLWH on dolutegravir gained 6.0 kg compared with 2.6 kg for NNRTI (p<0.05), and 0.5 kg for elvitegravir (p<0.05).

"Treatment-naïve PLWH starting dolutegravir-based regimens gained significantly more weight at 18 months than those starting NNRTI-based and elvitegravir-based regimens," investigators concluded.

Jason Schafer, PharmD, MPH, BCPS-AQ ID, BCIDP, AAHIVP, associate professor and clinical pharmacy specialist in HIV ambulatory care at Thomas Jefferson University, and Contagion® Section Editor of HIV/AIDS, explained the clinical significance of the findings for the community of HIV care providers.

“Weight gain is very common after initiating ART. In those with advanced disease who are underweight when starting therapy, weight gain can prolong survival. On the other hand, in those who are overweight or obese, weight gain with ART can increase risks for diabetes, hypertension, and cardiovascular disease,” Schafer said.

“The results of several observational studies now suggest that integrase inhibitor-based ART may be associated with greater weight than comparator regimens; and dolutegravir may be associated with the most weight gain,” he continued. “The mechanisms, risk factors, consequences, and extent of INSTI-associated weight gain remain unclear. Clinically, [although] weight gain may be more common with INSTI-based ART, these regimens are also commonly more effective, safer, and better tolerated than their comparators, which will continue to tip the scales in favor of their use.”