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Recovery of replication-competent HIV despite prolonged suppression of plasma viremia.

Science (New York, N.Y.)

therapeutic use, CD4-Positive T-Lymphocytes, immunology, virology, Coculture Techniques, Drug Resistance, Microbial, genetics, Drug Therapy, Combination, HIV Infections, drug therapy, HIV-1, isolation & purification, physiology, Humans, Immunologic Memory, Indinavir, Anti-HIV Agents, Lamivudine, Lymphocyte Activation, Mutation, RNA, Viral, analysis, blood, T-Lymphocyte Subsets, Viral Load, Viremia, Virus Activation, Virus Latency, Virus Replication, Zidovudine

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      Abstract

      In evaluating current combination drug regimens for treatment of human immunodeficiency virus (HIV) disease, it is important to determine the existence of viral reservoirs. After depletion of CD8 cells from the peripheral blood mononuclear cells (PBMCs) of both patients and normal donors, activation of patient CD4 lymphocytes with immobilized antibodies to CD3 and CD28 enabled the isolation of virus from PBMCs of six patients despite the suppression of their plasma HIV RNA to fewer than 50 copies per milliliter for up to 2 years. Partial sequencing of HIV pol revealed no new drug resistance mutations or discernible evolution, providing evidence for viral latency rather than drug failure.

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      9360926

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