Discovery presents new challenges to efforts to eradicate HIV -
The most critical barrier to cure HIV-1 infection is the presence of the viral reservoir cells in which the HIV virus can remain dormant for many years and avoid elimination by antiretroviral drugs. Very little was known when and where the viral reservoir is established during acute HIV-1 infection, or the extent to which it is sensitive to early antiretroviral therapy (ART).
Now, a research team led by investigators at Beth Israel Medical Center Deaconess (BIDMC) in collaboration with the US Military HIV Research Program showed that the viral reservoir is established surprisingly soon after the virus simian immunodeficiency intrarectal (SIV) infection of rhesus monkeys and before detectable viremia
results appear online in the journal Nature .
"Our data show that in this animal model, the viral reservoir was seeded much earlier after infection than previously recognized," says lead author Dan H. Barouch, MD, PhD, Director Centre of virology and vaccine research at BIDMC and member of steering committee of the Ragon Institute of MGH, MIT and Harvard. "We found that the reservoir was created in the tissues during the first days of infection, before the virus has even been detected in the blood. "
This finding coincides with the news recently reported the resurgence of HIV in the" Mississippi baby, "which was believed to have been cured by early administration of ART. "the sad news of the virus to rebound further in the child emphasizes the need to understand the early and refractory viral reservoir that is established very soon after HIV infection in humans" adds Baruch, a professor of medicine at Harvard medical School.
in this new study, the suppressive ART initiated scientific team into groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIV infection. Animals treated at day 3 after infection showed no evidence of virus in the blood and does not generate specific immune response SIV. However, after six months of suppressive ART, all animals in the study had viral resurgence when treatment was stopped.
While early initiation of antiretroviral therapy has led to a delay in the time to viral rebound (the time taken for virus replication to be observed in the blood after stopping ART) compared to a later treatment, the inability to eliminate the viral reservoir with very early initiation of ART suggests that additional strategies are needed to cure HIV infection.
"remarkably early seeding the viral reservoir in the early days of infection was sobering and presents new challenges for HIV-1 eradication efforts," the authors write. "Overall, our data suggest that very early initiation of ART, ART prolonged period, and probably additional interventions that activate viral reservoir will be required for HIV-1 eradication."
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