A large clinical trial in South Africa and Uganda has shown that a twice-yearly injection of a new pre-exposure prophylaxis drug offers young women complete protection against HIV infection.
The trial tested whether injecting lenacapavir for six months would provide better protection against HIV infection than two other drugs, both taken as daily tablets. All three drugs are pre-exposure prophylaxis (or PrEP) drugs.
Physician-researcher Linda-Gail Bekker, principal investigator of the South African part of the study, tells Nadine Dreyer what makes this breakthrough so important and what to expect next.
Tell us about the trial and its objectives
The Purpose 1 trial with 5,000 participants took place at three sites in Uganda and 25 sites in South Africa to test the effectiveness of lenacapavir and two other drugs.
Lenacapavir (Len LA) is a capsid fusion inhibitor. It interferes with the HIV capsid, a protein shell that protects HIV’s genetic material and the enzymes needed for its replication. It is given just under the skin, once every six months.
The randomized controlled trial, sponsored by drug developer Gilead Sciences, tested several things.
The first question was whether a twice-yearly injection of lenacapavir was safe and would provide better protection against HIV infection as PrEP for women aged 16 to 25 than Truvada F/TDF, a widely used daily PrEP pill that has been available for more than a decade.
Second, the trial also tested whether Descovy F/TAF, a new daily tablet, was as effective as F/TDF. The new F/TAF has superior pharmacokinetic properties to F/TDF. Pharmacokinetics refers to the movement of a drug into, through, and out of the body. F/TAF is a smaller tablet and is used in men and transgender women in high-income countries.
The trial had three arms. The young women were randomly assigned to one of the arms in a 2:2:1 ratio (Len LA: F/oral TAF: F/oral TDF) in a double-blind manner. This means that neither the participants nor the researchers knew which treatment the participants were receiving until the end of the clinical trial.
In East and Southern Africa, young women are the most affected by new HIV infections. They also struggle to adhere to daily PrEP treatment, for a number of social and structural reasons.
During the randomized phase of the trial, none of the 2,134 women who received lenacapavir acquired HIV. The treatment was 100% effective.
In comparison, 16 of 1,068 women (1.5%) who took Truvada (F/TDF) and 39 of 2,136 (1.8%) who received Descovy (F/TAF) acquired HIV.
The results of a recent independent assessment by a data safety monitoring board led to a recommendation that the blinded phase of the trial be stopped and that all participants be offered the choice of PrEP.
This committee is an independent panel of experts set up at the start of a clinical trial. They review unmasked data at specific times during the trial to monitor progress and safety. They ensure that a trial is not continued if there is clear harm or benefit in one group compared to others.
What is the significance of these trials?
This advance gives great hope that we have a proven and highly effective solution.
prevention tool to protect people from HIV.
Last year, 1.3 million new HIV infections were recorded worldwide. While this is down from the 2 million infections recorded in 2010, it is clear that at this rate we will not reach the UNAIDS target for 2025 (fewer than 500,000 infections worldwide) or even the goal of ending AIDS by 2030.
PrEP is not the only prevention tool.
PrEP should be offered alongside HIV self-testing, access to condoms, testing and treatment of sexually transmitted infections, and access to contraception for women of reproductive age.
In addition, young men should be offered medical male circumcision for health reasons.
But despite these options, we have not yet reached the point where we are able to stop new infections, especially among young people.
For young people, the daily decision of whether to take a pill, use a condom or take a pill at the time of sex can be very difficult.
Scientists and HIV activists hope that having to make this “prevention decision” only twice a year could reduce unpredictability and barriers.
For a young woman who has difficulty getting to a clinic appointment in the city or who cannot keep her pills down without facing stigma or violence, an injection just twice a year is the option that could protect her from HIV.
What happens now?
The Purpose 1 trial is expected to continue, but now in an “open-label” phase. This means that study participants will no longer be “blinded”: they will be told whether they were in the “injectable” group, the oral TDF group, or the oral TAF group.
They will be offered the choice of PrEP they prefer as the trial continues.
A sister trial is also underway: Objective 2 is being conducted in a number of regions, including some sites in Africa, among cisgender men and transgender and non-binary people who have sex with men.
It is important to conduct trials in different groups because we have seen differences in effectiveness. Whether the intercourse is anal or vaginal is important and may impact effectiveness.
How long will it take before the drug is marketed?
We read in a press release from Gilead Sciences that in the coming months, the company will submit the dossier with all the results to a number of country regulatory agencies, including the Ugandan and South African regulators.
The World Health Organization will also review the data and may make recommendations.
We then hope that this new drug will be adopted in WHO and country guidelines.
We also hope that the drug will be tested in more studies to better understand how to integrate it into real-world settings.
Price is a critical factor in ensuring access and distribution in the public sector where it is desperately needed.
Gilead Sciences said it would offer licenses to companies that make generic drugs, another key way to lower prices.
In an ideal world, governments could purchase this vaccine at an affordable price and offer it to everyone who wants and needs protection against HIV.
Linda-Gail Bekker, Professor of Medicine and Deputy Director of the Desmond Tutu HIV Centre at the Institute of Infectious Diseases and Molecular Medicine, University of Cape Town
This article is republished from The Conversation under a Creative Commons license. Read the original article.