Lenacapavir as pre-exposure prophylaxis for HIV prevention

Area of Science:

• Infectious Diseases
• Virology
• Pharmacology

Background:

• Sub-Saharan Africa bears a disproportionate burden of HIV, with young women and girls most affected.
• Low global uptake of pre-exposure prophylaxis (PrEP) and suboptimal adherence in vulnerable populations necessitate innovative strategies.
• Long-acting formulations, such as lenacapavir, offer a promising alternative to daily oral PrEP.

Purpose of the Study:

• To evaluate the efficacy and safety of long-acting injectable lenacapavir for HIV prevention.
• To compare lenacapavir with existing oral PrEP regimens and other long-acting injectables.
• To assess benefits and harms, including new HIV infections, adverse events, and mortality.

Main Methods:

• A systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted.
• Searches included CENTRAL, PubMed, and trial registers up to May 2025.
• Two RCTs involving 8660 participants compared injectable lenacapavir with oral PrEP (F/TDF or F/TAF).

Main Results:

• Lenacapavir demonstrated a large reduction in new HIV infections at 52 weeks compared to oral PrEP (RR 0.07, high-certainty evidence).
• A slight reduction in serious adverse events (SAEs) was observed with lenacapavir (RR 0.78, high-certainty evidence).
• Lenacapavir showed little to no difference in overall adverse events (AEs) but increased injection site reactions (moderate-certainty evidence).

Conclusions:

• Injectable lenacapavir is highly effective in preventing HIV infections, offering a significant improvement over oral PrEP.
• While injection site reactions are more common, lenacapavir is generally well-tolerated, with rare discontinuations.
• Lenacapavir represents a crucial advancement in HIV prevention, particularly for individuals struggling with daily oral adherence.