A large clinical trial in South Africa and Uganda has shown that a twice-yearly injection of a new pre-exposure prophylaxis drug provides young women with complete protection against HIV infection.
The trial examined whether a six-monthly injection of lenacapavir would provide better protection against HIV infection than two other drugs, both daily pills. All three drugs are pre-exposure prophylaxis (or PrEP) medications.
Physician-scientist Linda-Gail Bekker, lead investigator of the South African part of the study, tells Nadine Dreyer what makes this breakthrough so significant and what to expect next.
Tell us about the test and what is its purpose?
The Aim 1 trial was conducted at three locations in Uganda and 25 locations in South Africa with 5,000 participants to test the efficacy of lenacapavir and two other drugs.
Lenacapavir (Lane LA) is a fusion capsid inhibitor. It interferes with the HIV capsid, a protein shell that protects HIV’s genetic material and the enzymes needed for replication. It is injected just under the skin once every six months.
The randomized controlled trial, sponsored by drug developer Gilead Sciences, tested several things.
The first was whether a six-monthly injection of lenacapavir was safe and would provide better protection against HIV infection for women aged 16 to 25, compared with Truvada F/TDF, a daily PrEP pill that is widely in use and has been available for more than a decade.
Secondly, the trial also examined whether Descovy F/TAF, a new daily pill, was as effective as F/TDF. The new F/TAF has better pharmacokinetic properties than F/TDF. Pharmacokinetic means the movement of the drug into, through, and out of the body. F/TAF is a smaller pill and is used among men and transgender women in high-income countries.
The trial had three arms. Young women were randomly assigned to one of the arms in a 2:2:1 ratio (Len LA: F/TAF oral: F/TDF oral) in a double-blinded manner. This means that neither the participants nor the researchers knew which treatment the participants were receiving until the clinical trial ended.
In eastern and southern Africa, young women are the population that bears the brunt of new HIV infections. For a variety of social and structural reasons, they also find it challenging to maintain a daily PrEP routine.
During the randomized phase of the trial, none of the 2,134 women who took lenacapavir developed HIV infection. Its effectiveness was 100 percent.
By comparison, 16 (or 1.5%) of 1,068 women who took Truvada (F/TDF) and 39 (or 1.8%) of 2,136 women who took Descovy (F/TAF) became infected with the HIV virus.
The results of a recent independent data safety monitoring board review recommended that the “blinded” phase of the trial should be stopped and all participants should be offered the option of PrEP.
This board is an independent committee of experts appointed at the start of a clinical trial. They look at unblinded data at scheduled times during the trial to monitor progress and safety. They ensure that the trial does not continue if there is a harm or clear benefit in one arm compared to the others.
What is the significance of these tests?
This success raises great hope that we have a proven, highly effective prevention tool to protect people from HIV.
There were 1.3 million new HIV infections worldwide last year. Although this is less than the 2 million infections seen in 2010, it is clear that at this rate we will not meet the HIV new infection target set by UNAIDS (less than 500,000 globally) by 2025 or possibly even the goal of ending AIDS by 2030.
PrEP isn’t the only prevention tool.
PrEP should be provided alongside HIV self-testing, access to condoms, testing and treatment for sexually transmitted infections, and access to contraception for women of childbearing potential.
Additionally, young men should also be given access to medical male circumcision for health reasons.
But despite these options, we are not yet at the point where we can prevent new infections, especially among young people.
For young people, the daily decision of whether to take the pill, use a condom or have sexual intercourse can be very challenging.
HIV scientists and activists hope that allowing young people to make this “prevention decision” just twice a year could reduce unpredictability and barriers.
For a young woman who struggles to get an appointment at a clinic in the town or who cannot afford medication without facing stigma or violence, twice-a-year injections are the only option that can keep her free from HIV.
what happens now?
The plan is that the Objective 1 trial will continue, but now in an “open label” phase. This means that study participants will be “unblinded”: they will be told whether they have been in the “injectable” or oral TDF or oral TAF groups.
They will be given the option of PrEP of their choice as the trial continues.
Another trial is also underway: Aim 2 is being tested among cisgender men, and transgender and nonbinary people who have sex with men, in several regions, including some places in Africa.
It is important to test across different groups because we have seen differences in effectiveness. Whether the sex is anal or vaginal is important and may impact effectiveness.
When will the medicine come into the market?
We read in the press statement from Gilead Sciences that in the next few months the company will submit the dossier with all the results to regulators in several countries, specifically the Ugandan and South African regulators.
The World Health Organization will also review the data and may issue recommendations.
We hope that this new drug will be included in the World Health Organization and country guidelines.
We also hope that this drug will be tested in more studies to better understand how to incorporate it into the real world.
Price is a critical factor in ensuring access and delivery to the public sector where it is desperately needed.
Gilead Sciences has said it will license its products to companies that make generic drugs, another important way to lower prices.
In an ideal world, governments would be able to purchase it at affordable rates and it would be made available to everyone who wants it and needs protection from 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.
(Except for the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)
