Lenacapavir: A potential game-changer in HIV prevention – what stands in the way?

Leora Pillay is the Lead: HIV Prevention Advocacy, and Clare Morrison, Senior Advisor: HIV Prevention Advocacy at Frontline AIDS.

Initial results from the LEN-LA PURPOSE 1 trial are very promising. This study, involving 5,300 HIV-negative cisgender women aged 16 to 25 in Uganda and South Africa, found that LEN-LA is both highly effective and safe, with no HIV infections reported amongst the study participants.

These results are reinforced by promising initial findings from the PURPOSE 2 trial, focusing on cisgender men who have sex with men, transgender men, transgender women, and non-binary people from Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. In this trial, 99.9% of people remained HIV-negative, with only two cases of HIV infection amongst 2,180 participants. In both trials, the independent monitoring board recommended ending the blind phase of the trial early and offering open-label LEN-LA to all participants.

Researchers are conducting further trials among cisgender women and are testing LEN-LA in other populations including people who use drugs. The results from these studies are expected towards the end of this year and should provide further insights into LEN-LA’s effectiveness for different communities.

Could this be a game-changer?

Unlike daily oral PrEP or cabotegravir (CAB-LA), which requires administration every two months, LEN-LA only needs to be injected twice a year. Having a longer dosing interval is hugely advantageous. It means fewer trips to the clinic, and it is more discreet. LEN-LA is also another option to add to the HIV prevention toolbox, ultimately giving people more choice, flexibility and control over their health.

Why does this breakthrough matter?

This announcement is timely, given the alarming UNAIDS data presented at the recent International AIDS conference. Although there has been a slight decline in HIV incidence in Sub-Saharan Africa, globally we are still grappling with a serious HIV prevention crisis, with 1.3 million people acquiring HIV in 2023. In at least 28 countries, the number of new HIV cases is rising, as key populations — including men who have sex with men, trans and gender diverse people, sex workers and people who use drugs — and their sexual partners remain overlooked by many HIV programmes.

At the same time, new HIV infections among adolescent girls in Sub-Saharan Africa are still alarmingly high, with around 340,000 new cases reported last year alone. While new infections are declining faster among young men, evidence shows that young women, and especially adolescent girls, remain disproportionately affected.  

For Frontline AIDS partners working to address the prevention crisis, making new HIV prevention technologies like LEN-LA accessible to all could potentially be a game–changer, but there are many obstacles to overcome.  

What have we learned from previous innovations?

While innovations like LEN-LA hold great promise, the trajectory of other recent advances in HIV prevention, such as CAB-LA and the dapivirine ring, suggests that we must balance our optimism with determination. Despite its initial approval in 2021, CAB-LA has yet to reach many of the countries where Frontline AIDS and our partners work, including those involved in the trials.

The current insufficient supply of CAB-LA looks likely to extend until 2027, and affordability remains a significant issue. Approval and funding for the dapivirine ring across Africa also remain massive obstacles to getting the tool into communities.

The ongoing challenges with CAB-LA underscore the need for early planning for the introduction of LEN-LA. Frontline AIDS and many of our partners from around the world have challenged Gilead, the company that has developed LEN-LA, on its plans to restrict the production of low cost, generic versions of LEN-LA. After recently withdrawing from negotiations with the Medicines Patent Pool, Gilead has committed solely to voluntary licenses, typically granted to a limited number of companies, which are unlikely to support the large-scale production needed. Additionally, Gilead has chosen to postpone seeking regulatory approval for LEN-LA and plans to implement a yet-to-be-disclosed tiered pricing model that will set prices for low- and middle-income countries. From past experience, tiered prices are often significantly higher than the price that could be achieved through generic production. In middle-income countries, these prices are frequently unaffordable.

Combined, these approaches risk delaying LEN-LA’s rollout and limit its availability to high-incidence, low-resource countries. This means many middle-income countries are excluded, including those in regions with rising HIV rates, such as Latin America, Eastern Europe, Central Asia, and the Middle East and North Africa region. Rita Wahab, the Regional Coordinator of MENA Rosa highlighted that “The MENA region is in crisis with rising HIV incidence. Gilead’s decision on delaying the rollout of Lencapavir to various regions will delay our ability to prevent HIV and continue to fuel inequality such as the denial of the rights of women at risk to access PrEP, resulting in further HIV infections in the MENA region.”

Should LEN-LA only be approved as PrEP for key populations, this strategy will miss people vulnerable to HIV infection in the regions where it is approved, as well as key populations outside of these regions.

What should happen next?

While celebrating scientific breakthroughs like LEN-LA is important, substantial changes are needed to ensure its success. Expanding options alone will not meet global targets. These products must be approved and accessible at large scale, with affordable prices. We also need to plan more proactively to speed up regulatory approvals and ensure successful real-world implementation.

To achieve this, Gilead must prioritise access to LEN-LA for communities when making licensing, approval, and pricing decisions, especially in regions with rising HIV epidemics. A broader, open licensing approach through the Medicines Patent Pool (MPP) could help to increase timely and low-cost production of LEN-LA and to accelerate its distribution, with game-changing potential for the 1.3 million people currently acquiring HIV each year.

Ensuring that LEN-LA reaches those in urgent need requires more than just innovation; it demands a commitment to accessibility, to affordability, and to truly centering the voices, needs and perspectives of communities and people on the frontline.