Title |
The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy
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Published in |
Nature Medicine, January 2000
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DOI | 10.1038/71577 |
Pubmed ID | |
Authors |
Bharat Ramratnam, John E. Mittler, Linqi Zhang, Daniel Boden, Arlene Hurley, Fang Fang, Catherine A. Macken, Alan S. Perelson, Martin Markowitz, David D. Ho |
Abstract |
Replication-competent HIV-1 can be isolated from infected patients despite prolonged plasma virus suppression by anti-retroviral treatment. Recent studies have identified resting, memory CD4+ T lymphocytes as a long-lived latent reservoir of HIV-1 (refs. 4,5). Cross-sectional analyses indicate that the reservoir is rather small, between 103 and 107 cells per patient. In individuals whose plasma viremia levels are well suppressed by anti-retroviral therapy, peripheral blood mononuclear cells containing replication-competent HIV-1 were found to decay with a mean half-life of approximately 6 months, close to the decay characteristics of memory lymphocytes in humans and monkeys. In contrast, little decay was found in a less-selective patient population. We undertook this study to address this apparent discrepancy. Using a quantitative micro-culture assay, we demonstrate here that the latent reservoir decays with a mean half-life of 6.3 months in patients who consistently maintain plasma HIV-1 RNA levels of fewer than 50 copies/ml. Slower decay rates occur in individuals who experience intermittent episodes of plasma viremia. Our findings indicate that the persistence of the latent reservoir of HIV-1 despite prolonged treatment is due not only to its slow intrinsic decay characteristics but also to the inability of current drug regimens to completely block HIV-1 replication. |
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Mendeley readers
Geographical breakdown
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Japan | 1 | <1% |
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Student > Ph. D. Student | 21 | 20% |
Student > Master | 15 | 14% |
Other | 8 | 8% |
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Other | 13 | 12% |
Unknown | 13 | 12% |
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Mathematics | 3 | 3% |
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