Results of a phase 3 PURPOSE 1 HIV prevention study done among adolescent girls and young women in South Africa and Uganda show that there were no HIV infections in HIV-negative women who received 6 monthly (twice yearly) injectable investigational drug Lenacapavir - an injectable form of PrEP (pre-exposure prophylaxis) drug developed by Gilead Sciences. In other words, an HIV negative woman will need just two injections a year of this long acting drug to remain safe from acquiring HIV through the sexual route.

An independent Data and Safety Monitoring Committee found this new regimen to be safe and 100% effective, with no infections seen among study participants, and recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants. 

Mitchell Warren, Executive Director of AVAC, calls this as one of the most important results we have seen to date in an HIV prevention study. “Adding additional HIV prevention options means more people may find an option that is right for them. Beyond expanded choice, a twice-yearly injection has the potential to transform the way we deliver HIV prevention to people who need and want it most – from an easier to follow regimen for individuals to a decreased burden on healthcare systems that are stretched to the limit”, he said. 

PURPOSE 1 is a phase-3, double-blinded, multi-centre, randomised study to evaluate safety and efficacy of twice yearly long-acting injectable lenacapavir, and daily oral Descovy (emtricitabine and tenofovir alafenamide) for pre-exposure prophylaxis in adolescent girls and young women at risk of HIV infection. 

The study enrolled over 5,300 cis-gender adolescent girls and young women aged 16-26 years across 25 sites in South Africa and 3 sites in Uganda. The participants were randomised into 3 groups in a 2:2:1 ratio. 

- The 1st group received twice-yearly Lenacapavir, 

- The 2nd group took once-daily oral Descovy (emtricitabine and tenofovir alafenamide), and 

- The 3rd group was given once-daily oral Truvada (emtricitabine and tenofovir disoproxil fumarate).

There were zero incident cases of HIV infection among 2,134 women in the Lenacapavir group and 16 incident cases among 1,068 women in the Truvada group. HIV incidence in the Descovy group was numerically similar (39 incident cases among 2,136 women) to that in the Truvada group.

The results demonstrated superiority of twice-yearly injectable Lenacapavir over once-daily oral Truvada or Descovy. 

In the study, Lenacapavir, Descovy and Truvada - all were generally well-tolerated and no new safety concerns were identified. 

Access barriers need to be dismantled if the best of health services have to reach everyone equitably

Deep rooted gender and structural inequalities and poverty deny many women and adolescent girls their sexual rights, deprive them of their bodily autonomy, and expose them to various forms of physical and emotional violence, as well as heighten the risk of HIV - especially in low- and middle-income countries. 

As per UNAIDS data, globally 4000 adolescent girls and young women (aged 15–24 years) were infected with HIV every week in 2022, and more than 80% of them live in sub-Saharan Africa. In this region, there were 210,000 new HIV infections among adolescent girls and young women in 2022. The new long acting PrEP can go a long way in controlling new HIV infections in young women and girls - provided we also dismantle patriarchy and remove all other access barriers.

A companion phase 3 study, PURPOSE 2, is underway in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the US, testing twice-yearly lenacapavir for PrEP among cis-gender men who have sex with men, transgender women, transgender men, and gender non-binary people. Results from this study are expected by early 2025.

The regulatory filing for lenacapavir for PrEP will include the results of both PURPOSE 1 and currently-underway study PURPOSE 2 (if positive) to ensure that Lenacapavir can be approved for multiple populations and communities that are most in need of additional HIV prevention options.

Eliminate delays in rolling out new health technologies

Many countries have not yet fully rolled out existing PrEP (or not rolled it out at all in public services). Every new HIV infection that occurs, is a grim reminder we could have done better in terms of prevention - and more importantly - in making prevention services accessible to all with equity and dignity.

Regulatory agencies must start preparing to fast track regulatory review and introduction plans for the twice yearly long acting injectable Lenacapavir. Also, communities, policy makers, funders and programme implementers must start to re-design HIV prevention programmes and prepare health systems to be able to deliver the new drug- once it is approved- to the people for whom it is intended, without unnecessary delays. 

Lessons learned from the rollout of daily oral PrEP, and, more recently, the Dapivirine vaginal ring and injectable Cabotegravir, can help speed regulatory approval and guideline development in key countries, as well as community understanding and acceptance of Lenacapavir for PrEP.

"There is no time to waste if we are to translate these exciting clinical trial results into actual public health impact and expand the toolbox of HIV prevention choices," says Mitchell Warren of AVAC. 

For the unversed, PrEP helps prevent people from getting HIV. It is for people who are HIV-negative, but are at risk of getting HIV. It means taking prescription medicine routinely before exposure to HIV to prevent getting it. The most common way to get HIV is through sex or injection drug use. PrEP can reduce the chance of getting HIV through sex by 99%. It also reduces getting HIV from injection drug use by at least 74%. However, PrEP medication does not protect against other sexually transmitted infections.