Research led by the Frederick National Laboratory for Cancer Research (FNL) and Gilead Sciences shows the potential for a new drug that might only need to be taken twice a year to prevent HIV infection. The drug manufacturer is planning a clinical trial.  

The drug, Lenacapavir, recently approved by the Food and Drug Administration as a treatment for multi-drug resistant HIV infection, can be taken twice a year instead of daily, like most other antiretroviral drugs that fight AIDS. 

The research on Lenacapavir seeks to extend its use beyond that of a treatment to that of a preventative for HIV. The study, conducted in monkeys, focused on blocking intravenous viral transmission, which would be specifically relevant to people who inject drugs and are vulnerable to HIV. 

"We didn't want too many variables," said study co-leader Gregory Del Prete, Ph.D. of FNL's AIDS and Cancer Virus Program. "We have the most experience with intravenous infection for the virus used for this study, and injection drug use is one important element in how the [AIDS] pandemic is sustained." About 10% of new HIV cases occur through intravenous transmission. 

The research group tested Lenacapavir using a genetically altered version of HIV, which allows the virus to grow in certain monkey species – something HIV-1 itself cannot do. The virus (stHIV-A19) is 94% identical to HIV-1. They used stHIV-A19 in pigtail macaques, instead of using simian immunodeficiency virus (SIV) in rhesus macaques, the most common model for AIDS studies, because SIV is much less sensitive to Lenacapavir than HIV and may not accurately reflect how Lenacapavir will perform against HIV. Their findings appeared in the September 2023 issue of eBioMedicine

First the group demonstrated that stHIV-A19 is as sensitive to Lenacapavir as HIV-1 is to the drug. Next, they demonstrated that Lenacapavir maintains high levels of drug in pigtail macaques for prolonged periods after injection. Then they went on to give Lenacapavir to the laboratory animals. Three received a single injection of the drug, four got a control injection, and three received a daily three-drug antiretroviral therapy designed to effectively block viral infection. All 10 were injected with the virus. In the animals that received Lenacapavir, virus injections occurred 30 days after the Lenacapavir injections. 

The four control animals became infected. But after more than a year, the three that received Lenacapavir remained uninfected, as did the ones receiving daily antiretroviral therapy. So, Lenacapavir performed just as well as daily antiretroviral therapy in blocking infection. 

"It's very potent, perhaps more potent than any HIV drug currently used in humans," Del Prete said. "Low levels of the drug are very effective." 

The Centers for Disease Control and Prevention estimates that people who inject drugs can reduce their risk of HIV infection by 74 percent to 84 percent by faithfully adhering to a daily preventative drug regimen. But they must strictly follow the daily schedule, or the protection can be lost. Some people do better than others with the day-to-day requirement, so a long-acting drug could overcome some of the limitations of the everyday regimen. 

“While reduction of sexual HIV-1 transmissions will be critical for substantially reducing the overall incidence of HIV-1 infection, reduced transmission rates in [people who inject drugs] will also contribute meaningfully to efforts to reduce the public health impacts of the HIV pandemic,” the scientists concluded. 

The research was a collaboration of Frederick National Laboratory, Gilead Sciences, and Rockefeller University. As a result of its findings, Gilead Sciences is opening a clinical trial to test Lenacapavir as a long-acting HIV preventative treatment for people who inject drugs.  

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