High Continued Adherence of Lenacapavir in Individuals Who Use Substances and Alcohol

Adherence for twice-yearly lenacapavir (Yeztugo) was over 90%—and in some cases higher—in individuals who engaged in recreational drug and alcohol use. This subset preliminary finding was part of Gilead’s PURPOSE 2 study (Figure). This adherence went across multiple doses.

“One of the great things that we found in this analysis is that adherence was sustained across multiple doses. So not only were people coming in to get their first dose of lenacapavir, but they were coming back at 6 and 12 months to get their second and third doses, and that was not affected by their substance use patterns,” said Jesse Clark, MD, MSc, professor in residence in the Department of Medicine within the Division of Infectious Disease and in the Department of Family Medicine at the David Geffen School of Medicine at UCLA in Los Angeles, California. “This is especially important because people who use substances are at highest risk for acquiring HIV, and their adherence to daily oral medications is often affected by their substance use patterns.”

According to Clark et al, “Of 2183 participants randomized to LEN [lenacapavir], 767/2061 (37.2%) reported any drug use, 17/2092 (0.8%) injected drugs, 409/2058 (19.9%) used stimulants, 33/2086 (1.6%) used opioids, and 841/2074(40.5%) had monthly or more binge-drinking episodes at baseline.”

Clark maintained that even with recreational drug and alcohol use, twice-yearly injections simplify the process of staying adherent. 

“They only need to get the injection once every 6 months, so they're much more likely to maintain adherence. And the great thing about this analysis showed that adherence was maintained across multiple follow-up visits,” he said.

Clark pointed out that an upcoming trial, the PURPOSE 4 study, will look at the safety and efficacy of lenacapavir among people who inject drugs.

Reference
Clark J, Agwu AL, Buchbinder S, et al. Favorable adherence and safety of twice-yearly subcutaneous lenacapavir for PrEP among PURPOSE 2 participants who used substances. Abstract presented at: IDWeek 2025; October 19-22, 2025; Atlanta, GA.