Full results confirm potential breakthrough in HIV prevention
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Key takeaways:
- No women who received an investigational HIV prevention drug acquired HIV in a phase 3 study.
- The drug lenacapavir is administered via injection just two times per year.
In June, Gilead Sciences announced that its investigational long-acting antiretroviral drug lenacapavir prevented 100% of new HIV infections during a phase 3 trial conducted among cisgender women in Africa.
Experts have heralded the result as another potential breakthrough in HIV prevention. Unlike oral PrEP, which has been available for more than a decade and must be taken daily, newer HIV prevention drugs can be administered as long-lasting injections, allowing people to go months between doses. One such injectable, ViiV Healthcare’s cabotegravir, is already approved by the FDA and is administered every 2 months.
Lenacapavir was developed to be administered in even longer intervals — every 26 weeks, or just twice per year — extending even further the time that a patient can go without receiving medication.
The medication appears to be a success. Positive interim data from the PURPOSE 1 trial that were first reported by Gilead in June have now been published in full in The New England Journal of Medicine and presented at a major scientific meeting, the International AIDS Conference in Munich.
The randomized trial enrolled more than 5,300 HIV-negative cisgender adolescent girls and young women aged 16 to 25 years in South Africa and Uganda and randomly assigned them in a 2:1:1 ratio to receive either subcutaneous injections of lenacapavir every 26 weeks or take one of Gilead’s daily oral PrEP medications — emtricitabine/tenofovir alafenamide fumarate (FTC/TAF) or emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).
None of the more than 2,100 participants who received lenacapavir in the trial acquired HIV, according to the researchers. Incident infections did occur among participants in the trial’s other two arms — 39 among more than 2,100 participants taking FTC/TAF and 16 among more than 1,000 participants who took FTC/TDF. The researchers noted that adherence to the oral medications was low.
Speaking to reporters before the conference, International AIDS Society President Sharon Lewin, PhD, deemed it “a truly extraordinary result.”
“It is very exciting that we could soon have an HIV prevention option that is safe, highly effective and can be given just twice a year,” Lewin said.
Lenacapavir was so effective that the randomized and blinded phase of the trial was stopped in June and participants in the daily oral PrEP arms were given the option beginning July 8 to receive injections of lenacapavir instead.
To boot, the study population of PURPOSE 1 was unique — not just for its inclusion of cisgender women, who are often excluded from HIV studies, but also because it was the first trial of an HIV prevention medication that intentionally included pregnant women, according to Gilead. The trial also enrolled participants from another subpopulation often left out of HIV research: adolescents.
“This trial sets a new benchmark on how prevention trials should be run,” Linda-Gail Bekker, MBChB, PhD, told reporters.
Bekker, who leads the Desmond Tutu HIV Centre at the University of Cape Town and is CEO of the Desmond Tutu Health Foundation, presented the findings from the trial at the conference.
“We rolled the age down to 16 and 17 years old, so we will have data in adults, in pregnant and lactating people and in minors,” Bekker explained.
According to Bekker, there are three other PURPOSE trials underway to assess lenacapavir in other populations. Gilead said it expects results from the second trial, PURPOSE 2, in late 2024 or early 2025 and will use those data — if they are positive — to submit regulatory filings to get lenacapavir approved for HIV PrEP, including in the United States, where it is already available as ART for patients whose HIV is resistant to other available therapies, or who are intolerant of other ART regimens.
As with other HIV medications, the cost of lenacapavir could be a barrier to uptake. In a statement, Gilead said “it is too early” to say how much the drug will cost, although the company has pledged to make it available in resource-limited countries with a high incidence of HIV by offering licenses to generic drug makers.
Bekker, a self-described advocate of low-cost HIV medications, told reporters that Gilead has also said it will offer tiered pricing for countries that contributed data to the PURPOSE trials.
“I feel very strongly that the countries that contribute these kind of data need to be in the line for access — if not first, then as soon as possible,” she said.
References:
- Bekker L-G, et al. Abstract SS0407. Presented at: AIDS 2024; July 22-26, 2024; Munich.
- Bekker L-G, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2407001.
- Updated statement on global access planning for lenacapavir for HIV prevention. https://www.gilead.com/news-and-press/company-statements/updated-statement-on-global-access-planning-for-lenacapavir-for-hiv-prevention. Published July 24, 2024. Accessed July 24, 2024.
Perspective
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Clinical research in HIV used to be so exciting! New drugs and new combinations along with the still-novel tool of accurate viral load testing enabled us to make huge strides in controlling the virus and allowed prolonged survival in patients with a previously relentlessly progressing fatal disease.
But exciting trial results are still a "thing" in our field! One of those breakthroughs is seen in the report from the PURPOSE 1 controlled, randomized trial of twice-yearly injected lenacapavir, a recently developed antiretroviral drug, compared with current oral daily drugs as PrEP in preventing new HIV infections in uninfected women and girls in Africa. While oral PrEP was again shown to be very effective, with 55 new infections among more than 3,200 participants, there were no infections — none — among the 2,134 participants randomly assigned to the long-acting injection arm. With no doubt, these results are a dramatic game-changer in the crucial issue of HIV prevention.
Although important questions remain — What will be the cost in low-resource settings? Will health care systems be able to implement such treatment efficiently? Will this prove effective in men? — we have entered a new era in global efforts to end the HIV epidemic. The study also raises the bar for any possible vaccine rollout. Unless a vaccine is 100% effective for life, many women might find twice-yearly PrEP an attractive alternative and its inclusion as background prevention for ethical reasons in vaccine trials will undoubtedly make those studies even more difficult than is now the case. But those challenges cannot reduce our excitement for this striking and encouraging report.
The HIV epidemic has been a scourge for over 40 years. Perhaps an end may be in sight.
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Bekker L-G, et al. Abstract SS0407. Presented at: AIDS 2024; July 22-26, 2024; Munich.
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