Exploring the impact of Cabotegravir‐Rilpivirine long‐acting on weight gain, body composition and quality of life in adults living with HIV

Introduction: Long-acting injectable antiretroviral therapy (ART) with Cabotegravir (CAB) and Rilpivirine (RPV) offers an alternative to daily oral regimens, improving adherence and patient satisfaction. However, its impact on body composition and metabolism remains underexplored. Methods: We conducted a prospective cohort study involving 29 people with HIV initiating CAB + RPV LA at a single centre in Italy. Body composition was assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) at baseline, 24 and 48 weeks. Anthropometrics, laboratory parameters and patient-reported outcomes were also collected. Statistical comparisons across time points were performed using paired tests (p < 0.05 considered significant). Results: At 48 weeks, weight and BMI remained stable. Waist circumference significantly decreased (median 97 (IQR 91–102) to 94 (IQR 89–98) cm, p = 0.026), with no significant change in total fat percentage or visceral adipose tissue. A modest but statistically significant increase in trunk/limb fat ratio (mean 1.19 (SD 0.39) to 1.25 (SD 0.41), p = 0.035). Lean mass and muscle function were unchanged. BIA findings confirmed stable fat mass and body water compartments. Virologic suppression was maintained in all participants throughout follow-up. High-density lipoprotein (HDL) cholesterol increased significantly, accompanied by a rise in total cholesterol, while low-density lipoprotein (LDL) cholesterol, triglycerides and the total cholesterol/HDL ratio remained stable. Serum creatinine significantly decreased, mainly among individuals switching from bictegravir- or dolutegravir-based regimens. Glycaemia, insulin, HOMA-IR, Metabolic Score for Insulin Resistance (METS-IR), liver enzymes and hepatic steatosis and fibrosis indices remained stable. Adverse events, mostly injection-site reactions, decreased over time. Only one participant discontinued treatment. Treatment satisfaction improved throughout the study. Conclusion: CAB + RPV LA was not associated with significant weight gain, clinically relevant changes in body composition or adverse metabolic effects over 48 weeks. Virologic suppression was maintained, renal laboratory parameters improved in prior INSTI users and treatment was well tolerated with increasing satisfaction. These findings support CAB + RPV LA as a safe, effective and metabolically neutral alternative to daily oral ART.