HIV Breakthrough: A large clinical trial in South Africa and Uganda has demonstrated that a twice-yearly injection of a new pre-exposure prophylaxis (PrEP) drug, lenacapavir, provides young women with total protection against HIV infection. During the randomised phase of the trial, none of the 2,134 women who received lenacapavir contracted HIV, showcasing 100% efficacy.
The Trial and Its Objectives in HIV Breakthrough
The Purpose 1 trial, involving 5,000 participants, took place at three sites in Uganda and 25 sites in South Africa. It aimed to test the efficacy of lenacapavir and two other PrEP drugs. Lenacapavir, a fusion capsid inhibitor, interferes with the HIV capsid—a protein shell that protects HIV’s genetic material and enzymes needed for replication. Administered just under the skin once every six months, lenacapavir was tested for its safety and effectiveness compared to Truvada (F/TDF) and Descovy (F/TAF), both daily pills.
The trial had three arms: participants were randomly assigned to receive lenacapavir, F/TAF oral, or F/TDF oral in a 2:2:1 ratio in a double-blinded fashion. This means neither the participants nor the researchers knew which treatment was being administered until the trial concluded.
Results and Significance in the HIV Breakthrough
The trial’s results were compelling. None of the women who received lenacapavir contracted HIV, while 16 of the 1,068 women (1.5%) who took Truvada and 39 of the 2,136 women (1.8%) who received Descovy contracted the virus. This led an independent data safety monitoring board to recommend stopping the trial’s blinded phase, offering all participants a choice of PrEP.
Linda-Gail Bekker, principal investigator for the South African part of the study, emphasized the significance of these findings. The breakthrough provides a highly effective prevention tool against HIV, which is crucial given that young women in eastern and southern Africa are disproportionately affected by new infections.
Challenges and Future Directions
What has been hindering the HIV Breakthrough? Despite existing prevention tools like PrEP, HIV self-testing, access to condoms, screening and treatment for sexually transmitted infections, and medical male circumcision, new infections, especially among young people, have not been eradicated. Daily preventive measures can be challenging for young people due to social and structural barriers. However, a twice-yearly injection like lenacapavir could reduce these barriers, offering a more practical prevention option.
Moving forward, the Purpose 1 trial will continue in an “open label” phase, where participants will be informed of their treatment group and can choose their preferred PrEP method. A sister trial, Purpose 2, is also underway among cisgender men, transgender, and nonbinary people who have sex with men.
Regulatory Review and Implementation of the HIV Breakthrough
Gilead Sciences plans to submit the trial results to regulators in Uganda, South Africa, and other countries within the next few months. The World Health Organization will also review the data and may issue recommendations. The hope is that lenacapavir will be adopted into WHO and national guidelines, making it accessible to those in need.
What lenacapavir means in the HIV Breakthrough
The introduction of lenacapavir as a twice-yearly injection represents a significant advancement in HIV prevention. By offering a highly effective, less burdensome prevention method, it holds the potential to dramatically reduce new HIV infections, especially among young women in high-risk regions. Ensuring affordability and accessibility through generic drug licensing and public sector distribution will be critical to maximizing its impact.
Linda-Gail Bekker, a prominent HIV researcher, has received honoraria for advisories from Gilead Sciences, ViiV Healthcare, and Merck Pty Ltd. She serves as a Professor of Medicine and Deputy Director of the Desmond Tutu HIV Centre at the University of Cape Town’s Institute of Infectious Disease and Molecular Medicine.
