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A large clinical trial in South Africa and Uganda found that twice-yearly injections of a new pre-exposure prophylaxis drug completely protected young women from HIV infection. The study tested whether a six-month injection of lenacapavir was more effective at protecting against HIV infection than two other drugs, both given once daily. All three medications are pre-exposure prophylaxis (or PrEP). Physician and scientist Linda Gale Becker, principal investigator in the South African part of the study, explains with Nadine Dreyer why this milestone is so important and what awaits us. Aim 1 study was conducted with 5,000 participants 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, the protein coat that protects HIV's genetic material and the enzymes needed for replication. It is injected directly under the skin every six months. A randomized controlled trial sponsored by drug developer Gilead Sciences tested several things.

First, the six-month injection of lenacapavir is safer and more effective against HIV infection than Truvada F/TDF, the currently widely used daily PrEP pill for PrEP in women ages 16 to 25. The question was whether it could be a good defensive effect. receive. More than 10 years. Second, the study also tested whether a new daily pill, Descovy F/TAF, was as effective as F/TDF. New F/TAF has better pharmacokinetic properties than F/TDF. Pharmacokinetics is the movement of drugs in, through and out of the body. F/TAF is a small pill used for trans men and women in high-income countries. The process consisted of three parts. Young women were randomly assigned to both groups in a double-blind manner in a ratio of 2:2:1 (Len LA: Oral F/TAF: Oral F/TDF). This means that neither the participants nor the researchers knew what treatment the participants were receiving until the end of the clinical trial. In East and Southern Africa, young women bear the brunt of new HIV infections. They also find it difficult to maintain daily PrEP treatment for social and structural reasons.

During the randomization phase of the study, none of the 2,134 women who received lancapavir became infected with HIV. The efficiency was 100%. In comparison, 16 of 1,068 women (1.5%) taking Truvada (F/TDF) and 39 of 2,136 women (1.8%) taking Descovy (F/TAF) became infected with HIV. The results of a recent independent review by the Data Safety Monitoring Board led to the recommendation to stop the “blind” phase of the study and offer all participants a choice of PrEP. This committee is an independent expert panel that is established at the start of the clinical trial. They will review unblinded data and monitor progress and safety at specific points during the study. They ensure that the process does not continue if the apparent harm or benefit to one arm is greater than the other. This development gives us great hope that we now have a proven and highly effective prevention tool to protect people from HIV. Last year, 1.3 million people worldwide were newly diagnosed with HIV. Although this is a decrease from 2 million in 2010, it is clear that in some cases UNAIDS continues to fall short of its target for the number of new HIV infections in 2025 (less than 500,000 people worldwide). The goal of eradicating AIDS may not even be achieved. 2030.

PrEP should be offered alongside HIV self-testing, access to condoms, screening and treatment for sexually transmitted infections, and access to contraceptives for women of childbearing age. In addition, young men should have access to medical male circumcision for health reasons. However, despite these options, we are not yet at the point where we can stop new infections, particularly among young people. It is very difficult for young people to decide every day whether to take the pill, use a condom or take the pill during sex. HIV scientists and activists hope young people realize these “prevention decisions” are made just twice a year to reduce unpredictability and barriers. For young women who have difficulty getting an appointment at a clinic in the city or who cannot take their medications without facing stigma or violence, preventing HIV infection with just two injections per year can be helpful. The Aim 1 trial is planned to continue, but is currently in the “open label” phase. This means that the study participants are “unblinded”. Participants were informed whether they were in the “injection” group, the oral TDF group, or the oral TAF group. As the trial progresses, you will be asked to select the PrEP you want. The trial against the sisters is also underway. Goal 2 is being implemented in many regions, including some settings in Africa, with cisgender men, transgender people and non-binary people who have sex with men.

It is important to conduct experiments between different groups because we observe differences in performance. Gender, whether anal or vaginal, is important and can affect performance. In a press release from Gilead Science, we read that the company will present a document containing all the results to regulators in several countries, particularly Uganda and South Africa, in the next two months. The World Health Organization can also review the data and make recommendations. We hope that this new drug will be included in the WHO and national recommendations. We hope that the drug will be tested in further studies to better understand how it can be used in practice. Cost is an important consideration when access and transport are urgently needed in the public sector. Gilead Sciences has announced that it will license companies to make generic drugs, another key way to keep prices low. In an ideal world, governments could afford it and make it available to everyone who wants and needs HIV protection.