How we know a new medicine is so effective at preventing HIV transmission

Professor Linda-Gail Bekker was the lead scientist on a large clinical trial that found an effective way for women to massively reduce their risk of contracting HIV. Archive photo: Ashraf Hendricks

• A large clinical trial found that a twice-yearly injectable drug is extremely effective at preventing HIV transmission to HIV-negative women.
• The trial was conducted in South African and Uganda. Over 5,000 girls and young women participated.
• But the drug, lenacapavir, is currently only available in some high-income countries, at the whopping price of over R800,000 per person per year.
• Yet a study has found it could be produced for about R700 per year.
• For that to happen, pharmaceutical giant Gilead Sciences will have to allow other companies to manufacture generic versions of the drug.

News that a twice-yearly injectable HIV drug was found to be 100% effective for preventing HIV transmission, in a recent study, conducted in South Africa and Uganda, headlined the recent AIDS2024 conference.

The drug is called lenacapavir. It can be used by HIV-negative women to prevent them from contracting HIV through sex. This is known as pre-exposure prophylaxis or PrEP.

Lenacapavir is a new type of HIV drug called a capsid inhibitor. It is very long-acting and is given as a subcutaneous injection (this means the injection is given in the fatty tissue, just below the skin) every six months.

After presenting the results from PURPOSE 1 at the AIDS2024 conference, lead researcher Linda-Gail Bekker from the Desmond Tutu HIV Centre, Cape Town, described them as “beyond wonderful”.

PURPOSE 1

PURPOSE 1 was a trial in which the volunteers were girls and young women aged 16 to 25 conducted in 25 clinics in South Africa and three in Uganda – where the annual incidence of HIV was at least 3.5% a year.

The participants were randomly assigned to receive either: (1) lenacapavir every six months, or (2) daily oral emtricitabine and tenofovir alafenamide, or (3) daily oral emtricitabine and tenofovir disoproxil fumarate. Everyone in the study received the alternate injectable or oral placebo. This is a dummy drug so that the participants and the researchers were “blind” to who received what.

This is known as a randomised, double-blind, placebo-controlled trial. It is the highest standard type of clinical trial in medicine.

Daily oral emtricitabine and tenofovir alafenamide PrEP is currently only approved for use in men and transwomen in high-income countries. So the study was also looking at this regimen in women.

Daily oral emtricitabine and tenofovir disoproxil fumarate is currently the most widely-used PrEP regimen and was included as the control (standard of care to compare the experimental drugs to).

The researchers measured the efficacy of lenacapavir and tenofovir alafenamide by comparing the incidence of HIV with the estimated background incidence (the rate of HIV in the population without PrEP) and also compared its efficacy to oral emtricitabine and tenofovir disoproxil fumarate.

Among 5,338 participants who were HIV-negative at the start of the study, there were 55 HIV infections: none in 2,134 participants in the lenacapavir group, 39 in 2,136 participants in the emtricitabine and tenofovir alafenamide group and 16 infections among 1,068 participants in the emtricitabine and tenofovir disoproxil fumarate group.

The HIV incidence with lenacapavir was significantly lower than background HIV incidence and that with emtricitabine and tenofovir disoproxil fumarate. The term “significantly” has a strict meaning in medical research. It means the result cannot reasonably be explained by chance. Lenacapavir injections are more effective than the oral regimens.

But, HIV incidence with emtricitabine and tenofovir alafenamide was not significantly different from background HIV incidence or that with emtricitabine and tenofovir disoproxil fumarate. (In other words, the difference between these two arms could simply be due to chance.)

Participant retention (when participants stay in the study) was high (over 90%) and similar across the groups.

More than 90% of lenacapavir injections were on time but adherence in the oral PrEP groups was low. Very few participants in both oral PrEP groups took even one or two pills a week (based on drug levels measured in dried blood spot samples in 10% of the group). Low drug levels of oral PrEP were highly significantly related to the risk of HIV.

Poor adherence will explain the poor results for the oral PrEP – which can be very effective if taken daily. Women’s uptake of and adherence to oral PrEP remains limited and these results only highlight the urgent need for long-acting options, such as lenacapavir.

The study generated results much earlier than expected. At the interim analysis (when the researchers look at how the different groups are doing part way through the study) in May 2024, when half the participants reached 52 weeks follow-up, they found that lenacapavir was so effective that the two groups receiving oral PrEP were stopped and lenacapavir was offered to everyone.

PURPOSE 1 did not require participants to use contraception (unless they wished to prevent pregnancy) – which is unusual in studies of new drugs. There were 510 pregnancies, including 193 in the lenacapavir group. Approximately half of these were still ongoing when the results were presented. This will provide important safety information about lenacapavir in pregnancy and during breastfeeding and this approach deserves praise and should be more common in studies of new drugs.

Since the AIDS2024 conference the study has also been published in the New England Journal of Medicine, the world’s leading medical journal.

Access and pricing

Lenacapavir for PrEP could be produced by generic manufacturers at a price of $35–40 (about R680) per person per year – according to data also presented at the conference.

This analysis reported that lenacapavir could achieve sufficiently low pricing to enable broad access worldwide.

But this would require the originator manufacturer, Gilead Sciences, to license pharmaceutical companies to manufacture generic lenacapavir. No such voluntary licence has yet been agreed to.

At the moment, lenacapavir is far too expensive for most countries. It is currently sold for treatment in high-income countries at the vast sum of up to $44,819 (over R800,000) per person per year.

Unsurprisingly PURPOSE 1 results, as well as the pricing analysis, have attracted a lot of attention, including from Winnie Byanyima, head of UNAIDS. In the AIDS2024 opening ceremony Byanyima called for immediate plans for global access to lenacapavir PrEP especially in the countries that took part in the research.

Polly Clayden has been writing about HIV for decades. She was a founder of the HIV advocacy organisation i-Base.

More about HIV

• South Africans are living longer, mostly thanks to HIV treatment 01 December 2023
• Court ruling means that pharmacists can prescribe to people with HIV 15 August 2023
• The maths that helped South Africa tackle HIV 29 March 2023

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