An experimental HIV antibody has successfully suppressed the deadly virus for six months without additional treatment, a trial in monkeys has found.
The therapy may have targeted the viral reservoir – populations of long-lived, latently infected cells that harbour the virus and that lead to resurgent viral replication when suppressive therapy is discontinued.
The findings may inform strategies that attempt to achieve sustained, drug-free viral remission in people living with HIV.
After receiving a course of antiretroviral therapy for their HIV-like infection, about half of a group of monkeys infused with a broadly neutralising antibody to HIV combined with an immune stimulatory compound suppressed the virus for six months without additional treatment.
“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, Director the US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
“The findings from this early stage research offer further evidence that achieving sustained viral remission without daily medication might be possible,” Fauci said.
“This potential application is yet another example of how the research community is using powerful, broadly neutralising antibodies in multiple experimental applications to protect against and treat HIV,” he said.
In the study, scientists from Beth Israel Deaconess Medical Center (BIDMC) led by Dan Barouch, first infected 44 rhesus macaques with simian human immunodeficiency virus (SHIV), an HIV-like virus commonly used in nonhuman primate studies.
They then initiated daily antiretroviral therapy (ART) during acute infection to suppress the virus to below detectable levels in the monkey’s blood.
After 96 weeks of continuous ART, researchers divided the monkeys into four equal groups: a group that received five infusions of the HIV bNAb known as PGT121; a group that received ten administrations of GS-9620, an immune stimulant under development at Gilead Sciences; a group that received both therapies; and a control group that received neither.
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.
The experiment was designed to determine whether this combination of antibody and immune stimulant could reduce the viral reservoir while virus replication was well controlled by 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.
“Our findings suggest that the development of interventions to activate and eliminate a fraction of the viral reservoir might be possible,” said Barouch.
“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,” he said.
Published Mar 5, 2018