Twice-yearly PrEP injections hailed as HIV prevention breakthrough

Findings presented at AIDS2024 suggest that twice-yearly PrEP injections could be a promising HIV prevention option for adolescent girls and young women.  

What is the research about? 

The PURPOSE I trial involved around 5,300 cisgender adolescent girls and young women (ages 16-26) in South Africa (25 sites) and Uganda (3 sites). The trial ran between 2021 and 2023. Its aim was to evaluate twice-yearly PrEP injections using the antiretroviral lenacapavir and a new version of daily PrEP pills.  

The women were split into three groups. One group received a lenacapavir PrEP injection in the abdomen every six months. One group were given daily PrEP pills using emtricitabine–tenofovir disoproxil fumarate (F/TDF). This is the standard PrEP pills formula. The third group were given PrEP pills containing emtricitabine/tenofovir alafenamide (F/TAF), which is a newer type of regimen. 

All participants received one-to-one drug adherence counselling. They were also given placebo injections and pills to avoid study bias.  

Women who became pregnant were reassessed and given further information and counselling. They were allowed to continue in the trial if they wanted to. 

Why is this research important? 

Around the world, more than 6 million people have used PrEP pills. But research suggests that taking daily PrEP pills and getting refills can be hard to do due to practical issues and stigma.  

PrEP injections provide an alternative to PrEP pills. Injections are more discrete to use than daily medication. They are also more convenient because they last longer. The longest-acting PrEP injection currently available is cabotegravir. This can be given every other month. Now a number of countries have approved twice-yearly PrEP injections and are running trials. These trials may result in six-monthly PrEP injections becoming widely available one day. AVAC has described this as “one of the most significant advances in HIV prevention in the history of the response”. 

What did they find out? 

During the study, 55 women got HIV. There were 0 infections among women in the lenacapavir group, 39 infections among women in the F/TAF group and 16 infections among women in the F/TDF (standard PrEP) group. 

For comparison, HIV incidence among adolescent girls and young women in the study areas was 2.4%. 

This means that lenacapavir injections were 100% effective. The twice-yearly injection was significantly better than either of the daily PrEP pills. This is because adherence was much lower in the daily PrEP pill groups than the injection group. Women in the PrEP pill groups with medium to good adherence (taking at least two to four PrEP pills per week) were significantly less likely to get HIV than women in those groups with low adherence.  

Mild injection-site reactions were the most common side effect. These were higher in the lenacapavir group (69%) than in the placebo injection groups (35%). The next most common side effects were headaches and urinary tract infections. No major safety concerns were found with any PrEP formula. 

There were 510 pregnancies during the trial. No birth-related safety concerns were reported. 

What does this mean for HIV services? 

These are encouraging results. If twice-yearly lenacapavir injections are approved for wider use in these and other countries, it will provide adolescent girls and young women (and potentially other people at high risk of HIV) with the most convenient and discreet PrEP option yet.  

The goal is to provide a range of HIV prevention options so that individuals can work out which one is the best for them. This includes the PrEP vaginal ring, PrEP pills and bi-monthly injections. You can read more about PrEP options on our page. There is also a shareable, easy-to-understand video that outlines the choices for young people 

It is also worth reading AVAC’s statement on how to speed up regulatory review and rollout for lenacapavir, and its joint civil society call to action which outlines what needs to happen next.