Twice-yearly lenacapavir for PrEP reduces HIV infections by 96%

Twice-yearly injections of the capsid inhibitor drug lenacapavir can prevent the vast majority of HIV infections, according to a Phase 3 clinical trial published Wednesday in the New England Journal of Medicine.

HIV pre-exposure prophylaxis (PrEP) has emerged as a crucial tool for fighting the global HIV epidemic, but researchers say daily pill regimens remain an obstacle to treatment adherence. "Long acting antiretrovirals have raised the bar with respect to the reach, efficacy and effectiveness that can be achieved in our efforts to prevent HIV," said Onyema Ogbuagu, MBBCh, associate professor of medicine and pharmacology at Yale School of Medicine and director of the Yale Antivirals and Vaccines Research Program, who was the senior author of the study.

The trial enrolled 3,271 cisgender men and gender-diverse people and compared HIV twice-yearly lenacapavir injection to background infection rates and to Truvada, a daily pill for PrEP. Researchers say among 2,179 participants in the lenacapavir group, they found only two incident HIV infections – a 96% reduction compared to background HIV incidence. The Truvada group had nine incident cases among 1,086 participants. No new or significant safety concerns were identified.

The trial found lenacapavir decreased HIV incidence by 89% compared to Truvada. "Our study showed that twice-yearly injectable lenacapavir, beyond protecting 99.9% of recipients from acquiring HIV, superiorly outperformed a standard of care oral comparator,  was safe and well tolerated," Ogbuagu said.

Researchers say the nine participants in the Truvada group who experienced incident HIV infection showed evidence of low or no treatment adherence, underscoring the importance of PrEP options that fit a variety of patients and lifestyles. "With these results, we now have a new, potent and proven tool that can allow us expand and strengthen efforts to end HIV transmission globally," Ogbuagu added.

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