Gilead Sciences’ GS-9620 spurred the immune systems of macaque monkeys infected with an HIV-like virus and led to sustained viral suppression in two of the animals for months after stopping antiretroviral (ARV) treatment, aidsmap reports. Researchers treated 11 SIV-infected macaques (SIV is a simian cousin of HIV) with one of two investigational toll-like receptors (TLR7 agonists) GS-986 or GS-9620, or a placebo. Findings were presented at the 2016 Conference on Retroviruses and Opportunistic Infections (CROI) in Boston.
The researchers began treating the monkeys with Truvada (tenofovir/emtricitabine) and Tivicay (dolutegravir) 65 days after they were infected with SIV; the animals all achieved and maintained viral suppression. After 467 days of infection, a respective two, two and three monkeys received GS-986 at 0.1 milligrams per kilogram, GS-9620 at 0.05 mg/kg, or a placebo every other week until they had received 10 doses. Then the animals received a three-month break from treatment, after which they returned to their same treatment protocol until they had received nine more doses, or 19 total. The four other monkeys were given GS-9620 at 0.15 mg/kg every other week for 10 doses, then received a seven-month break and did not start up again on GS-9620.
At the end of these protocols, all the animals were taken off Truvada and Tivicay.
The researchers found that the repeated doses of GS-986 or GS-9620 led to viral blips, or transient virus replicating to the point of detection. The blips stopped after doses 11 through 19. Two of the nine monkeys that received the TLR7 agonists—one was given 0.1 mg/kg of GS-986 and the other GS-9620 at 0.15 mg/kg—have maintained a fully suppressed viral load for at least three months after stopping ARV treatment. The TLR7-treated monkeys showed little to no change in their interferon-alfa levels, while showing increased immune activation, including in CD4 and CD8 cells.
The experimental treatment was well tolerated.
GS-9620 has entered a Phase 1b clinical trial in HIV-positive humans receiving ARV treatment. In addition, the treatment is currently in a Phase II trial as a hepatitis B virus (HBV) treatment.
To read the aidsmap article, click here.
To read a Gilead press release on the research, click here.
To read the conference abstract, click here.