1581. Weight and Metabolic Changes with Long-Acting Lenacapavir in a Combination Regimen in Treatment-Naïve People with HIV-1 at Week 80
Authors: Kumar Princy N , Goldstein Deborah A , Hengel Richard L , Gaur Aditya H , Wurapa Anson K , Khalsa Ann M , Newman Cheryl L , Saunders Gary , Liu Shan-Yu , Dvory-Sobol Hadas , Rhee Martin , Gupta Samir K 
Published: November 2023

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 &gt;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 (Table).

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.

Disclosures
Princy N Kumar, MD, Gilead Sciences, Inc: Grant/Research Support|Gilead Sciences, Inc: Stocks/Bonds|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Stocks/Bonds|Pfizer: Stocks/Bonds|Theratechnologies: Advisor/Consultant|Theratechnologies: Grant/Research Support|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Stocks/Bonds Aditya H Gaur, MD, Gilead Sciences, Inc (Grant support/CTA with St. Jude): Grant/Research Support|Janssen (Grant support/CTA with St. Jude): Grant/Research Support|Viiv (Grant support/CTA with St. Jude and Serve on Pediatric Advisory Board): Board Member|Viiv (Grant support/CTA with St. Jude and Serve on Pediatric Advisory Board): Grant/Research Support Anson K Wurapa, MD, Gilead Sciences, Inc: Clinical Trial Investigator Ann M. Khalsa, MD, Gilead Sciences, Inc: Advisor/Consultant|Gilead Sciences, Inc: Grant/Research Support|Gilead Sciences, Inc: Honoraria|Glaxo Smith Kline: Advisor/Consultant|Viiv: Advisor/Consultant Cheryl L Newman, MD, Gilead Sciences, Inc: Grant/Research Support|GSK Viiv: Grant/Research Support|GSK Viiv: Honoraria|Janssen: Grant/Research Support|Merck: Grant/Research Support Gary Saunders, BSc, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Shan-Yu Liu, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Hadas Dvory-Sobol, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Martin Rhee, MD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Samir K. Gupta, MD, Gilead Sciences: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support