[ad_1]
A large clinical trial in South Africa and Uganda has shown that a twice-a-year injection of a new pre-exposure prophylaxis drug provides young women with complete protection against HIV infection. The trial examined whether a six-month 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, chief investigator for 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 test and what is its purpose?
The Aim 1 trial with 5,000 participants was conducted at three sites in Uganda and 25 sites in South Africa to test the efficacy of lenacapavir and two other drugs. lenacapavir (Len LA) is a fusion capsid inhibitor. It interferes with the HIV capsid, a protein shell that protects HIV’s genetic material and enzymes needed for replication. It is injected just under the skin once every six months. The randomized controlled trial, sponsored by drug developers 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 randomised to one arm in a 2:2:1 ratio (lane 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 number of social and structural reasons, they also find it challenging to maintain a daily PrEP regime.
During the randomized phase of the trial, none of the 2,134 women taking lenacapavir developed HIV. It had 100 percent efficacy. By comparison, 16 (or 1.5%) of the 1,068 women taking Truvada (F/TDF) and 39 (1.8%) of the 2,136 women taking Descovy (F/TAF) became infected with the HIV virus. Results of a recent independent data safety monitoring board review recommended that the “blinded” phase of the trial should be stopped and all participants be given 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 breakthrough raises great hope that we have a proven, highly effective prevention tool to protect people from HIV. Last year there were 1.3 million new HIV infections worldwide. 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 for 2025 (less than 500,000 globally) 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. In addition, young men should be offered medical male circumcision for health reasons. But despite these options, we have not reached the point where we are able to prevent new infections, especially among young people.
For young people, the daily decision to take the pill or use a condom or when to have sex can be very challenging. HIV scientists and activists hope that young people may find that making this “prevention decision” only twice a year can reduce unpredictability and barriers. For a young woman who struggles to get an appointment at a clinic in a city or who cannot take the pills without facing stigma or violence, the twice-a-year injection is the only option that can keep her free from HIV.
what happens now?
The plan is that the Aim 1 trial will continue, but now in the “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 choice of whichever PrEP they prefer as the trial continues. Another trial is also underway: Aim 2 is being conducted 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 Gilead Sciences’ press statement that in the next few months the company will submit dossiers with all the results to regulators in several countries, especially 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 adopted in WHO and country guidelines.
We also hope that we will see this drug tested in more studies to better understand how to incorporate it into real-world situations. Price is a key factor in ensuring access and distribution in the public sector where it is most needed. Gilead Sciences has said it will license it to companies that make generic drugs, which is another important way to bring down prices. In an ideal world, governments would be able to purchase it affordably and it would be given to everyone who wants it and needs protection from HIV.
[ad_2]
