A systematic review of evidence on weight change following initiation of long-acting cabotegravir for the prevention or treatment of HIV.

Abstract

Background: Weight gain is an increasingly recognized concern among people receiving antiretroviral therapy (ART) and may increase the risk of non-communicable diseases. Integrase inhibitors (INSTIs) such as dolutegravir (DTG) have been associated with weight gain, but the metabolic effects of long-acting cabotegravir (CAB-LA), another INSTI, for HIV treatment and prevention remain incompletely characterized. We conducted a systematic review to synthesize evidence on weight and body mass index (BMI) changes associated with CAB-LA-based regimens across ART and pre-exposure prophylaxis (PrEP) trials.

Methods: We systematically searched major biomedical databases, Medline, Embase, Cochrane CENTRAL, supplemented by Google Scholar and proceedings from key HIV conferences to identify grey literature for randomized controlled trials that evaluated CAB-LA as PrEP or CAB-LA-based regimen as ART between 01st January 2010 to 01st August 2025, with no language restrictions. Two reviewers independently screened studies, extracted data and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Given substantial heterogeneity in outcome reporting across studies, evidence was synthesized narratively following the Synthesis Without Meta-analysis (SWiM) guidance. Findings were summarized by intervention type (PrEP or ART), sex/gender and geographical setting.

Results: Of 1998 records identified, 234 were removed as duplicates, 1764 were screened at title and abstract level, and 42 full-text articles were assessed. This resulted in 11 reports from eight randomized controlled trials, with follow-up ranging from 41 to 185 weeks. Overall, weight remained stable or only increased modestly in both intervention and comparator groups across studies. Among HIV-negative individuals receiving CAB-LA for PrEP, weight gain was observed in both intervention and comparator groups, with no consistent evidence of excess weight gain attributable to CAB-LA. In HPTN 077, weight gain was similar between CAB-LA and placebo recipients, while HPTN 083 and HPTN 084 reported annualized weight gains ranging from 1.23 to 2.4 kg/year in CAB-LA recipients and 0.37 to 2.1 kg/year in comparator groups. Among people living with HIV receiving ART, weight changes at 48 weeks ranged from -0.4 to +1.8 kg with CAB-LA plus long-acting rilpivirine (RPV-LA) and 0.0 to +1.5 kg with comparator regimens, with no consistent evidence of greater weight gain in the CAB-LA plus RPV-LA arms. Only one trial among ART-experienced adults in Africa (CARES) reported greater weight gain with CAB-LA plus RPV-LA than with continued oral therapy (mean weight gain 1.5 kg vs. 0.0 kg, respectively), with more pronounced effects in women compared to men (2.1 kg vs. -0.2 kg). The overall risk of bias was low to moderate.

Conclusions: CAB-LA-based regimens were associated with only small increases in weight in both the prevention and treatment of HIV, with no consistent evidence of excess weight gain relative to standard comparators. Continued monitoring will be important as long-acting antiretroviral therapies are scaled up, particularly among women and individuals from Africa.