A large clinical trial in South Africa and Uganda has shown that a twice-yearly injection of a new pre-exposure prophylaxis (PrEP) drug provides young women with total protection against HIV infection. This trial brings new hope for HIV prevention, particularly for young women in regions heavily affected by the virus.
Key Findings:
- Trial Details: The Purpose 1 trial involved 5,000 participants and tested the efficacy of lenacapavir and two other PrEP drugs.
- Lenacapavir Efficiency: None of the 2,134 women who received lenacapavir contracted HIV, demonstrating 100% effectiveness.
- Comparison: In contrast, 16 of the 1,068 women taking Truvada (F/TDF) and 39 of the 2,136 women on Descovy (F/TAF) contracted HIV.
The Trial’s Significance
Trial Structure and Goals
The Purpose 1 trial was conducted at three sites in Uganda and 25 sites in South Africa. The trial aimed to test the efficacy of lenacapavir, a fusion capsid inhibitor, compared to Truvada (F/TDF) and Descovy (F/TAF), both daily pills. Lenacapavir interferes with the HIV capsid, preventing the virus from replicating.
Randomized Controlled Trial
Participants were randomly assigned to one of three groups in a 2:2:1 ratio:
| Group | Treatment |
|---|---|
| Lenacapavir | Injection every six months |
| F/TAF | Daily oral pill |
| F/TDF | Daily oral pill |
Neither participants nor researchers knew which treatment was being received until the trial concluded.
Target Population
Young women, aged 16 to 25, bear the brunt of new HIV infections in eastern and southern Africa. Daily PrEP regimens are challenging to maintain due to social and structural barriers, making a biannual injection an attractive alternative.
Results and Implications
Efficacy and Safety
The trial’s randomised phase showed lenacapavir’s 100% effectiveness in preventing HIV. By comparison, the infection rates for Truvada and Descovy were 1.5% and 1.8%, respectively.
Impact on HIV Prevention
The independent data safety monitoring board recommended ending the trial’s blinded phase due to lenacapavir’s clear benefit. All participants will now be offered a choice of PrEP.
Broader Significance
This breakthrough is a significant step towards reducing new HIV infections, aligning with UNAIDS goals to lower global new infections to under 500,000 by 2025 and to end AIDS by 2030.
Future Directions
Open Label Phase
The Purpose 1 trial will continue in an open label phase, where participants will know their treatment group and can choose their preferred PrEP method.
Additional Research
A sister trial, Purpose 2, is underway among cisgender men, transgender, and nonbinary people who have sex with men. This trial will further explore lenacapavir’s effectiveness in different populations.
Regulatory Approvals
Gilead Sciences plans to submit trial results to regulators, including those in Uganda and South Africa. The World Health Organization will also review the data and may issue recommendations.
Access and Affordability
Gilead Sciences intends to offer licenses to generic drug manufacturers to reduce costs. Affordable pricing is crucial for widespread access, particularly in public sectors where the need is greatest.
Long-Term Impact
Ideally, governments will purchase lenacapavir at affordable prices, offering it to all who need protection against HIV. This new drug has the potential to transform HIV prevention and significantly reduce new infections globally.
The success of lenacapavir in the Purpose 1 trial marks a major advancement in HIV prevention. With 100% effectiveness in preventing HIV in young women, this biannual injection offers a promising alternative to daily PrEP pills, addressing critical barriers to adherence. As regulatory reviews and further studies proceed, lenacapavir could become a key tool in the global fight against HIV.
Linda-Gail Bekker, the principal investigator for the South African part of the study, has received honoraria for advisories from Gilead Sciences, ViiV Healthcare, and Merck Pty Ltd. She is a professor of medicine and deputy director of the Desmond Tutu HIV Centre at the University of Cape Town.
