HIV Prevention Updated: WHO Suggests Yearly Doses of Lenacapavir Twice a Year
In a significant move to combat the global HIV epidemic, the World Health Organization (WHO) has issued new guidelines recommending the use of injectable lenacapavir as an additional option for pre-exposure prophylaxis (PrEP) to help prevent HIV. The recommendation is based on safety and efficacy findings from various studies and clinical trials, most notably PURPOSE 1 and PURPOSE 2.
Lenacapavir, marketed as Yeztugo for HIV prevention and Sunlenca for HIV treatment, is a novel antiviral medication belonging to the "HIV capsid inhibitor" class. It targets the HIV-1 capsid protein, a structure critical for viral replication and integration into human cells. Unlike most HIV medications, lenacapavir disrupts multiple essential processes, making it an attractive drug to study further.
In the PURPOSE clinical trials, investigators found an almost 100% reduction in new HIV infections among participants who received lenacapavir as a twice-yearly injectable. The FDA approved lenacapavir (Yeztugo) for PrEP in June 2025, making it the first bi-annual injectable HIV prevention option. This significantly reduces the frequency of dosing compared to oral daily or monthly injectable PrEP, which could improve adherence and access for at-risk populations.
The efficacy of lenacapavir has been remarkable in large clinical trials for both HIV treatment and prevention. In PURPOSE 1, a Phase III PrEP trial, there were no HIV infections in the lenacapavir arm, while early results from PURPOSE 2 showed only two infections among participants receiving the drug. These findings contributed to the drug being named "2024 Breakthrough of the Year" by *Science* magazine, highlighting its "astonishing 100% efficacy" in preventing HIV in one large trial in women and "99.9% efficacy in gender diverse people who have sex with men."
Lenacapavir for PrEP is given as two subcutaneous injections every six months, administered in the abdomen during a single clinic visit. The initiation regimen also includes oral tablets on the day of the first injection and the following day. This long-acting formulation is intended as a convenient and effective alternative for individuals who may struggle with daily or even monthly medication regimens.
The WHO's recommendation for lenacapavir comes as the number of new global HIV infections has decreased by about 39% since 2010, but there are still areas where numbers are increasing, making the need for HIV prevention critical. Paul E. Sax, MD, emphasizes the need for multiple options for preventing HIV among those at risk, including novel PrEP approaches like an investigational once-monthly pill for those who don't like or want injections.
While an effective HIV vaccine is not anticipated in the near future, the approval of lenacapavir marks a significant milestone in the global effort to reduce HIV transmission. It is crucial that everyone who is interested in lenacapavir will have access to it, and that all necessary pieces for initiating and continuing this new PrEP option are identified and rolled out equitably.
| Feature | Lenacapavir (Yeztugo) for PrEP | |-------------------------|----------------------------------------| | Mechanism of Action | Multi-stage capsid inhibitor | | Dosing | Two subcutaneous injections every 6 months (with oral initiation) | | Efficacy | 100% in PURPOSE 1, 99.9% in PURPOSE 2 | | Approval | FDA June 2025 (PrEP) | | Cross-resistance | None observed to date | | Breakthrough | Science “Breakthrough of the Year” 2024| | Convenience | Bi-annual, clinic-based |
- The World Health Organization (WHO) has recommended lenacapavir, marketed as Yeztugo for HIV prevention, as an additional option for pre-exposure prophylaxis (PrEP) due to its significant safety and efficacy findings.
- Lenacapavir, a novel antiviral medication, disrupts multiple essential processes that are critical for HIV replication and integration into human cells.
- In PURPOSE 1 and PURPOSE 2 clinical trials, lenacapavir showed almost 100% reduction in new HIV infections among participants, leading to its FDA approval for PrEP in June 2025.
- Science magazine named lenacapavir the "2024 Breakthrough of the Year", highlighting its astonishing efficacy in preventing HIV in large clinical trials.
- Lenacapavir for PrEP is a long-acting formulation given as two subcutaneous injections every six months, designed as a convenient and effective alternative for individuals who may struggle with daily or monthly medication regimens.
- As the number of new global HIV infections continues to decrease, the need for HIV prevention remains critical, and the WHO emphasizes the importance of multiple options like lenacapavir and investigational once-monthly pills for those who don't like injections.
- While an effective HIV vaccine is not imminent, the approval of lenacapavir marks a significant milestone in the global effort to reduce HIV transmission, with the goal that everyone who is interested in the drug will have access to it equitably.
