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

AUTHOR(S)
Ramratnam, Bharat; Mittler, John E.; Zhang, Linqi; Boden, Daniel; Hurley, Arlene; Fang, Fang; Macken, Catherine A.; Perelson, Alan S.; Markowitz, Martin; Ho, David D.
PUB. DATE
January 2000
SOURCE
Nature Medicine;Jan2000, Vol. 6 Issue 1, p82
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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[sup +] 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 10[sup 7] 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.
ACCESSION #
8817824

 

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