A viral reservoir of HIV-1, the umbrella term for the cells in which the virus lies dormant and out of reach of antiretroviral drugs, represents the most critical barrier to the development of a cure for HIV-1 infection. Very little has been uncovered about when and where a viral reservoir, also known as a latent reservoir, is established during acute HIV-1 infection, or the extent to which it is susceptible to early antiretroviral therapy (ART).
Now, in a study published online July 20 in Nature, a research team led by investigators at Beth Israel Deaconess Medical Center report that a viral reservoir is established strikingly early after intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before detectable viremia. For this work, the Beth Israel Deaconess scientists collaborated with colleagues in the U.S. Military HIV Research Program.
“Our data show that a viral reservoir was seeded substantially earlier after infection than was previously recognized,” says team leader Dan Barouch ’99, an HMS professor of medicine and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess. “A reservoir was established in tissues during the first few days of infection, before the virus was even detected in the blood.”
This discovery coincides with recent reports of the resurgence of HIV in the “Mississippi baby,” who was thought to have been cured by early administration of ART. “This unfortunate news further emphasizes the need to understand the early and refractory viral reservoir that is established quickly following HIV infection in humans,” adds Barouch.
In this new study, the team administered ART to groups of monkeys on days 3, 7, 10, and 14 after intrarectal SIV infection. Animals treated on day three showed no evidence of viremia and did not generate any SIV-specific immune responses. Nevertheless, all of the animals in the study exhibited viral resurgence when treatment was stopped after six months.
“The seeding of a viral reservoir within the first few days of infection presents new challenges to HIV-1 eradication efforts,” says James Whitney, an HMS instructor in medicine at the Center for Virology and Vaccine Research at Beth Israel Deaconess, and lead author of the study. “Our data suggest that extremely early initiation of ART, extended ART duration, and probably additional interventions that activate a viral reservoir will be required for HIV-1 eradication.”
Image: Jan Hinsch/Science Source