In a study presented by lead author Dan Barouch, 5 of 11 monkeys that were treated with both a TLR7 agonist (GS-9620) plus a broadly neutralizing antibody (PGT121) did not rebound after stopping antiretroviral therapy.
After receiving a course of antiretroviral therapy for their HIV-like infection, 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. According to a press release, the therapy may have targeted the viral reservoir—populations of long-lived, latently infected cells that harbor the virus and that lead to resurgent viral replication when suppressive therapy is discontinued.
In the study, researchers 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.
Several different anti-HIV bNAbs are currently being tested in animal models and humans for both the prevention and treatment of HIV infection. Compared with ART, which needs to be taken daily, antibodies to HIV tend to last longer in the body and have shown promise as candidates for long-acting HIV therapeutics and prevention modalities. PGT121, the bNAb evaluated in this study, is being studied in two currently enrolling clinical trials in humans being conducted at Beth Israel Deaconess Medical Center.