Scientists have generally believed that HIV and its monkey equivalent, SIV, gain a permanent foothold in the body very early after infection, making it difficult to completely eliminate the virus even after antiretroviral therapy has controlled it. Now NIH-supported researchers report that SIV can become entrenched in tissues fewer than 3 days after infection, before the virus is detectable in blood plasma (the liquid part) or blood cells.
Led by Dan H. Barouch, M.D., Ph.D., of Beth Israel Deaconess Medical Center and the Ragon Institute, in collaboration with the U.S. Military HIV Research Program, the scientists infected 20 monkeys with a high dose of SIV and divided them into five groups. Four groups received triple-drug antiretroviral therapy for 6 months starting at 3, 7, 10 or 14 days after infection. The fifth group was not treated. The scientists tested the monkeys for SIV in their blood and tissues and for anti-SIV immune responses, and confirmed that the drug regimen fully suppressed viral replication in all the treated animals.
During treatment, testing detected immune responses to SIV in the blood of all monkeys except those that started treatment 3 days post infection. SIV DNA was detectable in cells of the gut and lymph nodes in all of the monkeys, and in blood cells of all but the day 3-treated monkeys.
After 6 months, the scientists halted treatment and the virus again became detectable in the blood of all the monkeys.
Together, these findings indicate that starting therapy for SIV 3 days post infection blunted the development of virus in blood but did not prevent it from establishing a permanent reservoir in tissues, including cells of the gut and lymph nodes. These data show that an irreversible viral reservoir is established very early following SIV infection in this animal model, and that early antiretroviral therapy therefore has a limited effect on the SIV reservoir in this model.
Whitney et al. Rapid seeding of the viral reservoir prior to SIV viremia in rhesus monkeys. Nature DOI: 10.1038/nature13594 (2014).
Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is available for comment.
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