Landmark Approval for HIV Prevention
In June 2025, the U.S. Food and Drug Administration (FDA) approved the twice-yearly injectable form of lenacapavir (Yeztugo) for HIV pre-exposure prophylaxis (PrEP). This approval was supported by data from the PURPOSE 1 and PURPOSE 2 Phase 3 trials, which showed high efficacy in diverse groups. In the PURPOSE 1 trial, cisgender women had 100% efficacy, while the PURPOSE 2 trial, including cisgender men, transgender women, and gender non-binary individuals, reported 96% efficacy. Lenacapavir is currently the only available twice-yearly HIV prevention option, potentially improving adherence compared to daily oral regimens.
Global Guidance and Expanded Access Efforts
Following FDA approval, the World Health Organization (WHO) recommended injectable lenacapavir for HIV prevention in July 2025. A key focus is global access, especially in countries with high HIV rates. Manufacturer Gilead Sciences is working with organizations like the Global Fund and PEPFAR to provide the drug at no profit in 120 countries until generic options are ready. Partnerships with generic manufacturers in India are also in place to speed up the availability of more affordable versions. These initiatives aim to make lenacapavir accessible and overcome cost barriers.
Latest Clinical Trial Findings
Ongoing research continues to evaluate lenacapavir. Data presented at CROI in March 2025 showed positive safety and efficacy results in adolescents. Adolescents in the PURPOSE 1 trial had similar drug levels and safety profiles to adults, with no HIV infections. Additionally, early results from a Phase 1 study explored investigational once-yearly lenacapavir, showing promising safety and pharmacokinetic data for a potentially even longer-acting option.
Preferences for Long-Acting PrEP
A sub-study of the PURPOSE 1 trial examined preferences for PrEP. Participants often preferred twice-yearly injectable lenacapavir over daily oral pills due to increased confidence in not missing doses, a greater sense of protection, and better compatibility with their lifestyles, particularly among adolescents.
Comparison of Major PrEP Options
Lenacapavir adds a new option to HIV prevention. Below is a comparison of common PrEP methods:
| Feature | Oral PrEP (e.g., Truvada, Descovy) | Long-Acting Injectable PrEP (Cabotegravir) | Long-Acting Injectable PrEP (Lenacapavir) | |
|---|---|---|---|---|
| Dosing Frequency | Daily oral pill | Every 2 months | Every 6 months | |
| Administration | Oral | Intramuscular injection | Subcutaneous injection | |
| Key Challenge | Adherence issues | Less frequent than oral, but more frequent than lenacapavir | High initial cost | Potential for resistance in rare cases |
| Trial Efficacy | High when adhered to | High in clinical trials | Extremely high (96–100%) in Phase 3 trials | |
| Availability | Widely available, generic options exist | Widely available since 2021 | Approved in 2025, rollout ongoing |
Future Implications and Ongoing Challenges
Lenacapavir's approval and WHO recommendation are significant for HIV prevention. Its long-acting nature could improve adherence, potentially impacting the epidemic, especially in underserved populations. Positive adolescent data is also important for this vulnerable group. Challenges remain, mainly regarding access and cost. The drug's success depends on global efforts to expand access and generic production to overcome the initial high price. Research into once-yearly versions continues to explore even more convenient options. Collaboration among governments, health organizations, and manufacturers is vital for lenacapavir to fulfill its potential in combating the HIV epidemic.
Conclusion
The latest news about lenacapavir injections is largely positive, highlighted by the June 2025 FDA approval for twice-yearly PrEP. This provides a highly effective, long-acting prevention method that can help overcome adherence and stigma challenges. Supported by WHO guidelines, promising adolescent data, and plans for global partnerships, the outlook for HIV prevention is improving. While cost is a major hurdle, efforts to make the drug accessible in resource-limited settings demonstrate a commitment to reaching those in need. The twice-yearly lenacapavir shot represents a new phase in the fight against HIV, with research already exploring even longer-lasting formulations.
