Antiretroviral Treatment Aimed at Primates Targets, Suppresses Viral Reservoir
HIV therapies have improved to the point that combinations of antiretroviral (ARV) drugs routinely knock down the virus so effectively that standard tests cannot detect it in the blood. Researchers have long sought strategies that would allow people to stop taking their ARVs without the virus rebounding—a functional rather than complete cure, because patients would still harbor the virus, which integrates its genes into the DNA of a host’s cells.
Yet save for a few notable exceptions, almost everyone who has stopped taking ARVs has seen the virus jump back to high levels a few weeks later. To keep the virus at bay, HIV-infected people must take ARVs for life.
Now, in a new study, approximately half of a group of monkeys infused with a broadly neutralizing antibody to HIV combined with an immune stimulatory compound suppressed the virus for six months without additional treatment.
The team from Beth Israel Deaconess Medical Center (BIDMC), supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) was led by Dan Barouch. They first infected 44 rhesus macaques with simian human immunodeficiency virus (SHIV).
Then they initiated daily antiretroviral therapy (ART
) during acute infection to suppress the virus to below detectable levels in the monkey’s blood- for 96 weeks. Researchers continued to administer ART throughout this period and afterward for 16 additional weeks. Antibody levels were undetectable for at least eight weeks prior to discontinuation of ART.After discontinuation of ART, virus rebounded in the blood of all 11 of 11 control monkeys after a median of 21 days. By contrast, six of 11 monkeys that received the combination of PGT121 and GS-9620 showed a delayed viral rebound after a median of 112 days, and five of 11 animals in the combination group did not rebound for at least 168 days after discontinuing ART.
The animals in the combination group that did rebound demonstrated viral loads that were more than 100-fold lower than the control group.
The monkeys treated with the combination also had markedly less viral DNA in their lymph nodes, suggesting that the reservoir was reduced but not eliminated.
The addition of GS-9620 appeared to extend both the length of viral suppression and the magnitude of reduction in the viral reservoir. Examining how this occurred, and expanding on this strategy, may help scientists determine a way to safely reduce the viral reservoir in humans, with the eventual goal of allowing people living with HIV to suppress the virus without regular medication.
“HIV excels at evading the immune system by hiding out in certain immune cells. The virus can be suppressed to very low levels with antiretroviral therapy, but quickly rebounds to high levels if a person stops taking medications as prescribed,” said Anthony S. Fauci, M.D., NIAID Director. “The findings from this early stage research offer further evidence that achieving sustained viral remission without daily medication might be possible. This potential application is yet another example of how the research community is using powerful, broadly neutralizing antibodies in multiple experimental applications to protect against and treat HIV.”
“Our findings suggest that the development of interventions to activate and eliminate a fraction of the viral reservoir might be possible,” said Dr. Barouch, principal investigator of the study and director of the Center for Virology and Vaccine Research at BIDMC. “Although we are still a long way off from having a cure for HIV, our data suggest a strategy for targeting the viral reservoir that can be further explored.”
