To Switch or not to Switch: are there any Antiretroviral Strategies to Attenuate Weight Gain in People with HIV?

Weight gain and development of obesity has been well-described with contemporary antiretroviral therapy (ART), and management has proven difficult. It remains unclear whether weight gain can be mitigated or reversed by switching ARV classes. We aim to summarize recent literature on ART switch to attenuate weight gain. Recent studies have recognized integrase strand transfer inhibitors (INSTI) and tenofovir alafenamide (TAF) as significant independent contributors to weight gain. The mechanisms for weight gain may stem from adipose tissue hypertrophy and fibrosis. The reversibility of the weight gain appears to be limited, with trials evaluating switching to more “weight-neutral” ART not proving effective. Discontinuing INSTI- and/or TAF-based regimens has not led to significant changes in weight, suggesting that alternative strategies may be required to modify weight trajectories in individuals who experience excessive weight gain after initiating INSTI-based ART.