In a significant leap forward in the fight against HIV, twice-yearly lenacapavir for prevention of the virus in cisgender women has been found to be safe and 100 percent effective as long-acting pre-exposure prophylaxis (PrEP), say the results from a recent Phase 3 clinical trial.

In trials conducted among young women in Uganda and South Africa, the injection administered only twice a year could herald a breakthrough poised to revolutionise HIV prevention strategies and has the potential to drastically reduce the rates of new infections among one of the populations with the highest infection rates on the continent.

Lenacapavir, a novel injectable antiretroviral medication, is a first-in-class capsid inhibitor that works by targeting the HIV capsid protein, a crucial component of the virus’s structure.

The drug acts at multiple steps in the life cycle of the virus, with the overall effect of inhibiting HIV-1 replication at both the early and late stages. By inhibiting this protein, lenacapavir prevents the virus from replicating and establishing infection within the host.

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Long-acting PrEP formulations are an important option for people who experience barriers to daily pill-taking.

Its long-acting formulation, requiring administration only twice a year, represents a significant advantage over current PrEP options that often require daily or more frequent dosing.

According to the paper published last week, by the National Institutes of Health (NIH)’s National Institute of Allergy and Infectious Diseases , not a single participant of the 2,134 women in the Phase 3 clinical trials that received lenacapavir contracted HIV, underscoring its efficacy and offering hope for a new era in HIV prevention.

By comparison, 16 of the 1,068 women (or 1.5 percent) who took Truvada, a daily pill that has been available for more than a decade taken daily against HIV infection, and 39 of 2,136 women (1.8 percent) who received a newer daily pill called Descovy were infected.

This 100 percent effectiveness rate is particularly noteworthy given the myriad challenges in preventing HIV transmission, including adherence to medication regimens and access to healthcare services. This represents a significant scientific advance for cisgender women, a population for whom biomedical HIV prevention evidence has been limited until now.

Gilead Sciences, Inc, the sponsor of the study, said Lenacapavir is administered every six months, making it the most durable HIV prevention method to have shown efficacy in this population.

The NIH-funded HIV Prevention Trials Network is implementing two Gilead-sponsored studies in the United States of lenacapavir in people who inject drugs, and is assessing its effectiveness in men who have sex with men, in transgender people.

Cisgender women, who have been disproportionately affected by the HIV epidemic, often face numerous barriers to effective HIV prevention, including socio-economic factors, limited access to healthcare, and gender-based violence. Lenacapavir’s bi-annual dosing schedule could alleviate some of these challenges by simplifying the prevention regimen and reducing the HIV burden on healthcare systems.

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Furthermore, participants in the trial reported minimal side effects, aligning with previous studies that have demonstrated the drug’s tolerability, a crucial aspect in ensuring that those at risk of HIV can use the drug without significant adverse effects, further supporting adherence and overall health outcomes.

However, while the trial results are promising, there are still hurdles to overcome before lenacapavir can be widely implemented.

Regulatory approvals, pricing, and ensuring equitable access are critical factors that must be addressed.

Long-acting cabotegravir, administered once every two months, already is used in the United States and is increasingly available in low- and middle-income countries. Cabotegravir is however currently priced at $22 200 per year, more than 185 times higher than the $60–$119 estimated cost-effectiveness threshold for middle-income countries (MICs).

The controlled-release monthly dapivirine vaginal ring is approved for HIV PrEP in cisgender women in several African countries.

The outstanding question is access, with Gilead charging $42,250 per patient per year for lenacapavir, in the United States, where it is approved as a treatment for HIV, the scientists in the NIH-funded Lenacapavir trial noted that equitable access is essential for realising the benefits of long-acting PrEP, particularly in geographic areas and among populations experiencing steady or increasing HIV incidence.