An HIV-like virus established a reservoir of latently infected cells within three days of infection among a group of monkeys in a recent study. Treating the virus with antiretrovirals (ARVs) for six months starting the day of infection or up to two days postinfection prevented viral rebound after treatment was interrupted, with a diminishing success rate the more treatment initiation was delayed.
In a previous study, researchers found that SIVmac251, an HIV-like virus engineered for research in nonhuman primates, established a reservoir within three days. After infecting rhesus monkeys rectally, the researchers started the animals on ARVs on days 3, 7, 10 or 14 following infection. Even treatment started as early as day 3 did not prevent viral rebound after ARVs were discontinued following six months of treatment.
Publishing their findings in Nature Communications, the research team conducted a similar experiment including four groups of five rhesus monkeys, which they started on treatment six hours after infection or on day 1, day 2 or day 3 postinfection. The animals were treated with daily injections of Truvada (tenofovir disoproxil fumarate/emtricitabine) plus Tivicay (dolutegravir). Their plasma viral load was monitored every two to four weeks throughout the study.
Before beginning ARVs, one monkey had a detectable viral load of 572 on day 3 after infection. All animals maintained an undetectable viral load throughout treatment.
Twenty-four weeks after starting them on ARVs, the study authors took all the animals off treatment. None of the five monkeys that started treatment the day of infection experienced viral rebound, compared with 20 percent (1 of 5), 60 percent (3 of 5) and 100 percent (5 of 5) of those started on treatment on day 1, day 2 and day 3 following infection, respectively. All viral rebounds occurred between 10 and 21 days after treatment was interrupted.
The scientists found a correlation between viral rebound and the integration of viral DNA in lymph node CD4 cells.
The study authors concluded, “These data demonstrate that the viral reservoir is seeded within the first few days of infection and that early ART initiation limits the viral reservoir.” However, they noted, “We cannot exclude the possibility that an extended period of [ARV treatment] suppression [of greater than] 6 months may reduce the frequency of viral rebound in the early treatment groups.”
To read the study, click here.