None of the over 2,000 young women and girls injected twice a year with a new drug, lenacapavir, contracted HIV in one of the most important advances in HIV prevention.

Gilead Sciences announced these results last Friday, reporting that its Phase 3 PURPOSE 1 trial, conducted in South Africa and Uganda involving 2,134 women and girls aged 16-25, had been so successful that it was terminating early.

Its announcement has been widely hailed as a huge breakthrough in the HIV sector where a vaccine has been elusive, and a range of groups urged Gilead to priorise early access to lenacapavir.

The injectable was compared with Truvada and Descovy, two pills taken daily that have proven successful as pre-exposure HIV prophylaxis (PrEP). 

Sixteen of the 1,068 women in the Truvada group and 39 of the 2,136 women in the Descovy group contracted HIV during the trial. 

During a scheduled review of results, the trial’s independent data and safety monitoring board (DSMB) found the lenacapavir regimen was safe and highly effective. The trial, expected to run until September, was terminated early based on its success. Results of the trial have not been peer-reviewed yet.

The age group targeted by the trial is the worst affected by HIV in southern Africa. In 2022, over three-quarters of infections in 15 to 24-year-olds in the region were girls and women, according to UNAIDS.

“Every week, 4,000 adolescent girls and young women aged 15–24 years became infected with HIV globally in 2022, and 3,100 of these infections occurred in sub-Saharan Africa,” added UNAIDS.

One of the ‘most important results’

“This is one of the most important results we’ve seen to date in an HIV prevention study,” said Mitchell Warren, executive director of AVAC, a non-profit HIV prevention advocacy organisation.

“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.” 

Professor Linda-Gail Bekker, director of the Desmond Tutu HIV Centre in South Africa, said that the twice-a-year injectable could provide a “critical new choice” to prevent HIV.

“While we know traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills, as well as potentially help increase PrEP adherence and persistence given its twice-yearly dosing schedule,” added Bekker.

Gilead expects results by early 2025 from the programme’s other trial, PURPOSE 2, which is assessing twice-yearly lenacapavir for PrEP in men who have sex with men, transgender and non-binary people, currently underway in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the US. 

Cost of access?

Lenacapavir (marketed as Sunlenca) was approved in the US in 2022  for “heavily treatment-experienced adults with multi-drug resistant  HIV-1 infection and for treatment of people living with HIV who have been on other HIV treatment regimes which are currently failing”.

However, Gilead charges $40,000 per patient per year in the US, reports aidsmap. 

When announcing the PURPOSE 2 results, Gilead acknowledged  the “importance of helping to enable access in order for twice-yearly lenacapavir for PrEP, if approved by regulatory authorities, to achieve the broadest impact”. 

“In light of today’s milestone and the company’s ongoing commitment to communities affected by HIV, Gilead intends to brief community partners and provide a public statement regarding its planned access approach for high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries,” said the company.

Gilead’s statement was welcomed by African HIV medicines access group AfroCAB in an open letter to its CEO, Daniel O’Day.

“Replacing 365 pills of oral PrEP with just two injections is a life-changing transition and urgently needed option, as millions of our brothers and sisters, friends, and neighbours face challenges of stigma, pill burden, and adherence, leaving them unprotected against HIV acquisition,” said AfroCAB.

“To forge a new pathway forward for [lenacapavir], we call on stakeholders to act now. After thousands of our community members have taken part in clinical trials for LEN and other injectable PrEP products, it is time that pharmaceutical companies, governments, and donors play their part in driving access among the communities that supported the science.”

“We expect to see a timeline that takes into account a full analysis of PURPOSE 1 data and the coming data from PURPOSE 2 from Gilead as soon as possible, and we urge regulatory agencies to prepare to fast track regulatory review,” Warren added.

“We also call on [the World Health Organization] to be prepared to quickly include lenacapavir, if approved by regulatory agencies, in HIV prevention guidelines. 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.”

Meanwhile, Unitaid urged Gilead to make access to lenacapavir a priority, calling for “the terms of their access strategies – including any voluntary licensing agreements – [to be] transparent, global health-oriented, and equitable”.

“Lack of prompt and broad action would jeopardise translating the clinical trial results into real-life impact,” said Unitaid, which offered to work with Gilead to enable access, including “quality-assured, low-cost generics”.

“Unitaid is dedicated to leveraging its recent investment through the Wits Reproductive Health and HIV Institute to facilitate market shaping interventions on long-acting PrEP options (in partnership with the Clinton Health Access Initiative), as well as its continued support to enabling elements such as the key work of WHO and the WHO Prequalification program, the Medicines Patent Pool and other intellectual property grants, to ensure access to this life-saving product is as broad as possible,” the organisation said in a statement last week.

Image Credits: Gilead, Diana Polekhina/ Unsplash.