Research carried out in infant macaques suggests that treatment with antiretroviral therapy plus three antibody therapies could permanently clear human immunodeficiency virus (HIV) from the body of infected newborn babies.
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, a cell-surface co-receptor used by most HIV variants transmitted at birth.
Notably, none of the individual treatments, or simpler two-drug combinations tested by the research team, reliably prevented infection from becoming established.
As reported in Nature Microbiology, 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.
“The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” said co-lead author Jonah Sacha, PhD, professor and senior researcher at Oregon Health & Science University, in a press statement. “The next step after that is to test if this can work in newly exposed adults.”
In this study, the researchers infected infant macaques with simian HIV to model babies infected with HIV. Despite advances in treatments and protection from HIV, more than 120,000 babies are born infected with the virus every year.
The team 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. Controls and animals who did not receive all three therapies did rebound after CD8-cell depletion.
The researchers are not exactly sure why this treatment combination works so well, but they think it might be linked to leronlimab’s ability to block HIV 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 blood stream.
“For reasons we don’t understand, HIV really wants to use CCR5 receptors to infect cells,” Sacha said. “By blocking access, it’s like you’ve kept fuel away from the fire.”
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 researchers note that their 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 the researchers plan to test if their treatment strategy can also be effective at a later stage of the disease.
“We only tested out to three days,” Sacha said. “Could it work a week after infection? Two weeks? How far can you go after infection, and still purge the virus?”
