Cancer drug venetoclax reduced HIV-infected cells in monkeys, offering potential cure research.
Researchers at Emory University have found that a cancer drug may help remove HIV-infected cells that can remain in the body even when treatment keeps the virus under control. These initial findings came from a study involving rhesus macaques and could offer a new direction in research toward an HIV cure. The drug, called venetoclax, is already approved for treating certain types of cancer and works by blocking a protein called Bcl-2, which helps cells stay alive. Researchers found that Bcl-2 also appears to help some HIV-infected cells remain alive for long periods.
One of the biggest issues in properly treating HIV is the viral reservoir. Antiretroviral therapy (ART) can lower HIV in the blood to very low levels, but it does not remove every infected cell. Some infected cells can remain hidden in the body for years. If ART is stopped, those cells can produce HIV again, causing the virus to return.
The Emory team wanted to see whether venetoclax could reduce this hidden pool of infected cells when treatment with ART was first started. The study used rhesus macaques infected with simian immunodeficiency virus, or SIV, which is commonly used in HIV research because it provides a useful model for studying how infection affects the immune system. Fourteen days after infection, the animals received either ART alone or ART combined with venetoclax. Those receiving the two drugs showed a faster drop in SIV-infected CD4 T cells than those animals receiving ART alone. CD4 T cells are an important part of the immune system and are among the cells targeted by HIV.
The researchers also found that the number of infected cells stayed lower in the animals that received venetoclax for months after the drug was stopped, while ART treatment continued. The result suggested that a short period of venetoclax treatment could have effects that lasted beyond the time when the drug was actually given. The study was only a proof-of-concept experiment, however. The macaques received venetoclax for just ten days, so the findings do not show that the drug can cure HIV in people. Animal studies also cannot predict every possible benefit or risk that could occur in human patients.
Researchers are now studying whether giving venetoclax for a longer period could reduce the HIV reservoir even further. The team is also looking at why some infected cells survive even when Bcl-2 is blocked. Two clinical trials are already underway to study venetoclax in people living with HIV. Those trials will provide more information about whether the drug can safely reduce HIV-infected cells in humans and whether the results seen in macaques can be repeated.
The research does not mean that people with HIV should stop taking ART or replace current treatment with venetoclax. ART remains the standard treatment for controlling HIV and stopping it without medical guidance can cause the virus to resurface quickly. Still, the findings give HIV researchers another possible way to address one of the hardest problems in HIV treatment. Instead of only keeping the virus suppressed, scientists are studying ways to remove the infected cells that allow HIV to remain in the body. If future human studies show that venetoclax can safely reduce this reservoir, the drug could become part of a larger treatment approach, moving one step closer to long-term HIV remission or even a cure.
Sources:
Cancer drug eliminates HIV-infected cells in animal model study
BCL-2 inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques
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