Weight Change with Long-Acting Cabotegravir Plus Rilpivirine in People with HIV: Targeted Review and Meta-Analysis

INTRODUCTION: Weight gain with modern antiretroviral therapy has raised concerns about long-term metabolic implications, particularly with integrase strand transfer inhibitor‑based regimens. However, evidence regarding the metabolic implications of long‑acting cabotegravir plus rilpivirine remains limited. This targeted review and meta-analysis aimed to evaluate weight outcomes in adults with HIV receiving long‑acting cabotegravir plus rilpivirine. METHODS: A targeted literature review was conducted via the PubMed database to identify peer-reviewed studies reporting changes in body weight among adults with HIV receiving long-acting cabotegravir plus rilpivirine. Studies that met predefined eligibility criteria underwent quantitative synthesis using random-effects meta-analysis. Among eligible studies, absolute weight change was stratified and evaluated at ≤1 year and >1 year; weight change relative to oral antiretroviral therapy controls was analyzed at ≤1 year. Moderator and exploratory regression analyses supplemented these findings as available. RESULTS: Long-acting cabotegravir plus rilpivirine was associated with a statistically significant mean weight increase at ≤1 year (0.92 kg; P = .006) compared to baseline. No significant differences in mean weight change were observed between long‑acting cabotegravir plus rilpivirine and oral antiretroviral therapy through ≤1 year (P = .225). At >1 year, long‑acting cabotegravir plus rilpivirine produced a significant pooled weight gain (P < .001), exceeding the ≤1-year pooled mean by approximately 1.3 kg. Moderator analyses indicated greater weight gain in cohorts with fewer male participants (P = .047); no differences were observed between once- and twice-monthly dosing. Compared with oral antiretroviral therapy controls, long‑acting cabotegravir plus rilpivirine was associated with greater weight gain in studies using mixed-class antiretroviral therapy comparators versus those using only integrase strand transfer inhibitor-based antiretroviral therapy regimens (P < .001). DISCUSSION: Long‑acting cabotegravir plus rilpivirine is associated with modest early weight gain that may increase with longer exposure. Limited evidence suggests similar weight-related outcomes to contemporary integrase strand transfer inhibitor‑based antiretroviral therapy regimens. Further research is warranted to better characterize mediators of weight gain and long-term metabolic implications associated with long‑acting cabotegravir plus rilpivirine use. CONCLUSION: These findings support the potential for progressive weight gain with prolonged use of long-acting cabotegravir plus rilpivirine and reinforce the importance of continued monitoring of weight-related changes in people with HIV receiving this regimen.