1581. Weight and Metabolic Changes with Long-Acting Lenacapavir in a Combination Regimen in Treatment-Naïve People with HIV-1 at Week 80

Abstract

Background: Lenacapavir (LEN) is a highly potent, long-acting, first-in-class inhibitor of HIV-1 capsid protein approved for the treatment of HIV-1 infection in adults with multidrug resistance in combination with other antiretrovirals. CALIBRATE is an ongoing phase 2 study in people with HIV-1 (PWH) who are newly initiating treatment. At Week 80 (W80), subcutaneous (SC) and oral LEN, in combination with other antiretrovirals, maintained high rates of virologic suppression. In PWH initiating treatment, weight increases associated with a return to health effect have been observed. This analysis examined weight and metabolic changes to the W80 timepoint. Methods: Participants were randomized (2:2:2:1) to 1 of 4 treatment groups (TG). TG1 and TG2 both received SC LEN (927 mg) every 6 months + oral once daily (QD) emtricitabine/tenofovir alafenamide (F/TAF) for 28 weeks, after which virologically suppressed participants continued a 2-drug maintenance regimen: SC LEN (927 mg) with oral QD TAF (TG1) or oral QD bictegravir (BIC) (TG2). TG3 received oral QD LEN + F/TAF, and TG4 received oral QD BIC/F/TAF throughout. The metabolic profile of LEN was assessed from baseline to W28 and after initiating the 2-drug maintenance regimen to W80. Due to the small sample size, no statistical testing was performed. Results: 182 participants (7% female, 52% Black) were randomized and dosed (n=52, 53, 52, 25 in TG1 to TG4, respectively). Baseline median age was 29 years; 15% had baseline viral load >100,000 c/mL. Baseline median weight and body mass index (BMI) were 78.2 kg and 25.8 kg/m2, respectively. Weight, BMI, and fasting lipid profiles for each treatment group through W80 are presented. Conclusion: In this phase 2 study of treatment-naïve PWH, treatment regimens that included SC or oral LEN in combination with other antiretroviral agents led to expected weight gain and increase in BMI, consistent with the return to health phenomenon, and were not associated with clinically relevant increases in lipids.