Researchers have made a promising discovery in the fight against HIV, with early research suggesting that a triple therapy could permanently clear the virus from the bodies of infected newborn babies. The treatment, which combines antiretroviral therapy with two broadly neutralizing antibodies and a third antibody that blocks CCR5, a cell-surface co-receptor used by most HIV variants transmitted at birth, has shown significant success in infant macaques.
The study found that none of the individual treatments or simpler two-drug combinations tested by the team reliably prevented infection from becoming established. However, the triple therapy treatment regime was able to prevent viral rebound in all eight animals that received it, even after antiretroviral treatment was stopped.
The treatment used by the investigators combined antiretroviral therapy with two broadly neutralizing antibodies that target the viral envelope, as well as leronlimab, an antibody that blocks CCR5. They tested a number of different treatment regimens 72 hours after exposure when viral infection was confirmed by blood test.
The infected monkeys were either assigned to a control group or given a standard three-drug antiretroviral regime daily for 27 weeks: tenofovir disoproxil fumarate, emtricitabine, and dolutegravir; a one-time injection of two broadly neutralizing anti-HIV-envelope antibodies: PGT121 and VRC07-523LS; and short-term treatment with leronlimab; or a combination of less than three of these treatments.
When the antibody levels were low enough to not be suppressing the virus, the antiretroviral treatment was stopped, and the animals were followed up for a year to monitor for virus rebound. In all eight animals who received the triple therapy, no viral rebound was seen after a year using various tests including CD8-cell depletion.
According to the report, this treatment regime still needs to be tested in humans, and the researchers acknowledge that it is possible that latent virus could be hiding in non-lymphoid tissues like the bone marrow or central nervous system. However, the research is undoubtedly promising, and co-lead author Jonah Sacha, PhD, professor and senior researcher at Oregon Health & Science University, said that the treatment could go to clinical trials immediately to eliminate HIV infection in newborns.
They think the treatment combination works so well because leronlimab blocks HIV from entering cells through the cell surface protein CCR5, combined with the ability of the other therapies to stop viral replication and reduce the amount of virus in the bloodstream. By blocking access, it’s like keeping fuel away from the fire, as HIV really wants to use CCR5 receptors to infect cells.
Most HIV transmitted in the womb uses CCR5 to enter cells, but a small percentage of HIV infections use the alternative co-receptor CXCR4, and some can use either. The approach likely would not work if the virus is entering cells via CXCR4. The study only tested animals in the early stages of infection, but they plan to test if their treatment strategy can also be effective at a later stage of the disease.
In practice, this development could mean that newborns infected with HIV may have a chance at a virus-free life, which would be a significant improvement over current treatment options. This could also have implications for the development of treatments for newly exposed adults. As Sacha said, the next step after testing this treatment in newborns is to test if it can work in newly exposed adults.
The team is now looking to test their treatment strategy at later stages of the disease, and Sacha said that they only tested out to three days, but they want to know if it could work a week after infection, two weeks, or even further after infection. The goal is to determine how far after infection the treatment can still purge the virus.
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Researchers like Sacha are making progress in the fight against HIV and other diseases, such as those related to aging, and their work is key to improving human health.
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