Beyond the Numbers: Weight Gain Risk Factors, Implications, and Interventions among Individuals with HIV

Abstract

Background: Advancements in antiretroviral therapy (ART) have significantly improved life expectancy, leading to an increased prevalence of older adults with HIV. This population may face challenges related to age-related comorbidities in addition to HIV and possibly antiretroviral therapy-related comorbidities. Among those, weight gain has emerged as an increasingly recognized problem raising clinical concern. This narrative review provides an overview of existing data and outlines risk factors, implications, and management strategies including ART switch, lifestyle modifications, and the use of weight-reducing pharmacologic agents. Body of evidence: Recent studies support the concept that weight gain following ART initiation is multifactorial and is associated with demographic-, HIV-, lifestyle-, and ART-related risk factors. Female sex, Black race, individuals presenting with low CD4 T-cell count and elevated HIV-1 viral load appear to be particularly susceptible to this weight gain. The impact of ART, including integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF), on weight gain is undergoing reassessment as accumulating evidence elucidates weight-suppressive effects of older agents like efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). In reviewing evidence from ART switch studies, concerns have emerged regarding whether ART directly causes weight gain among persons with HIV (PWH), or if the observed weight gain is a consequence of discontinuing older agents that previously mitigated such effects. Management strategies includes careful assessment of ART, striking a balance between efficacy and adverse effect profiles, and the use of weight loss pharmaceuticals as adjuncts to lifestyle modification through diet and exercise. Summary: Weight gain among PWH requires a comprehensive and individualized management approach which considers the unique needs of individuals with HIV. Risk factors for weight gain among PWH have been identified, however, the underlying mechanism remains poorly understood. More studies are needed to understand the pathogenesis of weight gain, individual variability, long-term implications on cardiometabolic factors and other comorbidities, and optimal management strategies.