Once-a-month HIV PrEP could be the future and replace daily pills
Women who are at risk of HIV infection and are using HIV pre-exposure prophylaxis (PrEP) on a daily basis might in the near future have to use only one pill a month, if a trial conducted in SA and other parts of the world is successful.
This week the efficacy study, which is led by the University of Washington, received a $122m grant from the Bill & Melinda Gates Foundation to test the effectiveness of a once-a-month oral pill to prevent HIV.
The five-year grant will support the implementation of a phase 3 randomised trial of an antiretroviral drug, islatravir, among women in seven countries in Sub-Saharan Africa — SA, Uganda, Kenya, Malawi, Eswatini, Zimbabwe, and Zambia.
Known as Impower 22, the clinical trial, which will start screening in Africa in June, will evaluate the efficacy and safety of monthly oral islatravir compared to a daily preventive pill. The study will involve 4,500 healthy, HIV-uninfected women aged 16 to 45.
About 4,000 will be from 21 African sites and 500 women will be from the US. Islatravir belongs to a new class of ARV drugs called NRTTIs (nucleoside reverse transcriptase translocation inhibitors) in development by Merck for the treatment and prevention of HIV infection.
Dr Connie Celum, lead investigator and professor of global health, medicine and epidemiology, described the study as having the potential to be a “game changer”. “The whole field is moving towards less adherence-dependent and easier strategies for users of HIV prevention.”
She said different formulations and delivery mechanisms are needed that are highly effective, safe and convenient for populations at increased risk for HIV infection.
“For some people, a daily pill is easy. But when you’re talking about populations where sexual activity is stigmatised, particularly young African women, men who have sex with men, or female sex workers, there are a lot of barriers to taking a pill a day,” she said.
The UN's global goal for 2020 was 3m oral PrEP users, but by the end of the year, fewer than 1m worldwide had started taking the pills. While the current standard of care — daily oral pills — effectively protects those who use it consistently, the ability of people to adhere to that regimen is a major concern.
A paper which Celum and her global health colleague Dr Jared Baeten penned last year found that some of the greatest doubts about taking PrEP were voiced by young African women, who account for about 25% of new HIV infections globally.
Participants in the study will receive either a daily dose of emtricitabine-tenofovir (which is approved as PrEP) and a placebo or islatravir once a month and a daily placebo that looks like emtricitabine-tenofovir. Researchers will then compare the rate of infection in the two trial arms. The overarching hypothesis is that monthly oral islatravir will be superior to the daily pill, as defined by HIV incidence, safety, and tolerability.
Enrolment will start with women aged 18 or above. Once the medication is deemed safe by an independent external data monitoring board, the younger end of the age range will be lowered from 18 to 16 to begin data collection on adolescent women. This will be one of the first studies that will give women who become pregnant the choice to continue with the drug under investigation or switch to open label daily emtricitabine-tenofovir.
Data from early phase studies have found islatravir to have the highest potency among current nucleoside analogues. It also has a favourable safety profile, lack of food requirements, and no significant interaction problems with other drugs. If the trial is successful, islatravir will be submitted to the US Food and Drug Administration for review.
“If we’re going to impact the HIV epidemic through prevention, we have to do it at a much larger scale. If you only had to take one little tablet once per month and not deal with daily pill-taking and storage, that’s a totally different ball game," said Celum.