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Early Establishment of a Viral Reservoir

August 15, 2014

Early Establishment of a Viral Reservoir

  1. Richard T. Ellison III, MD

Seeding of a viral reservoir occurs within 3 days after simian immunodeficiency virus infection of rhesus monkeys.

  1. Richard T. Ellison III, MD

The hope of curing early HIV infection depends on the ability of antiretroviral therapy (ART) to prevent development of a persistent viral reservoir. But how early does reservoir seeding occur? To answer this, researchers studied 20 rhesus monkeys that were inoculated intrarectally with simian immunodeficiency virus (SIV) and then either left untreated or given tenofovir, FTC, and dolutegravir for 24 weeks beginning 3, 7, 10, or 14 days after exposure.

ART initiated at 3 days prevented SIV viremia, as well as development of measurable humoral or cellular immune response, in four of four monkeys. In addition, SIV proviral DNA was never detectable in peripheral blood mononuclear cells in these animals. Proviral DNA was found in inguinal lymph node and colorectal gastrointestinal mononuclear cells while the monkeys were on ART, albeit at lower levels than in animals that were untreated or started on ART later after exposure. After ART was discontinued, SIV viremia was found in all of the exposed animals, although viremia onset was delayed in those started on treatment at 3 days.

Comment

This work suggests that with SIV, a persistent viral reservoir is established even before the onset of viremia. The findings complement early data from the New York Department of Health suggesting that postpartum AZT is most effective in protecting infants if given within 48 hours after birth (NEJM JW Infect Dis Jan 1 1999) and the recent report of HIV rebound in the “Mississippi baby,” who appeared to have been cured with ART initiation 30 hours after birth. Such early seeding of the viral reservoir highlights the necessity of starting postexposure prophylaxis for HIV as quickly as possible after exposure and reminds us how difficult it will be to cure HIV infection.

  • Disclosures for Richard T. Ellison III, MD at time of publication Grant / research support NIH-NIAID

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ADE LONGE Physician, Neurology

Intresting

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