Rebound of HIV and reappearance of HIV reservoirs in patients treated with IL-2& combination antiretroviral drugs following cessation of therapy

ll as therapies that preserve and enhance HIV-specific immunity."

In the current report, the authors discuss two patients treated with highly active antiretroviral therapy (HAART - three or more anti-HIV drugs including a protease inhibitor) for 33 and 30 months, respectively. Both patients also had received intermittent intravenous infusions of IL-2 for 42 and 50 months, respectively. Before discontinuing therapy, both had levels of HIV in their plasma below 50 copies per milliliter of blood, the detection limit of the viral load assay used in the study. IL-2 is a regulatory protein of the immune system that has potent effects on the proliferation, differentiation and activity of CD4+ T cells and other immune system cells.

The researchers then used a sensitive culture technique to look for replication-competent HIV in the resting CD4+ T cells from the blood of these individuals and found none - even when they cultured up to 330 million cells from each individual. They then performed lymph node biopsies on the two patients and still could not isolate viable HIV.

"In these patients, we observed both a reduction of plasma virus to less than 50 copies per milliliter of blood and a marked diminution of an important viral reservoir - the pool of latently infected, resting CD4+ T cells," says Dr. Chun. "But the question still remained whether levels of HIV would remain low following discontinuation of therapy."

"The answer, unfortunately, was a resounding no," he adds. "When these patients discontinued HAART, virus was detected in the plasma of both individuals within three weeks, and the pool of resting CD4+ T cells carrying replication-competent HIV emerged shortly thereafter."

Dr. Chun adds: "Our data suggest that there may well be other HIV reservoirs in addition to resting CD4+ T cells which are responsible for the rebound in plasma viremia, a hypothesis that will be illuminated by further studies."

Co-authors of Drs. Chun and Fauci i

Contact: Greg Folkers
NIH/National Institute of Allergy and Infectious Diseases

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