Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 8, Pages 4819-4824Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0736332100
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Funding
- NIAID NIH HHS [AI43752, U01 AI038858, AI51982, AI29164, K24 AI051982, U01 AI027670, R37 AI029164, AI36214, P30 AI036214, R01 AI043752, AI38858, AI27670] Funding Source: Medline
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Viral replication and latently infected cellular reservoirs persist in HIV-infected patients achieving undetectable plasma virus levels with potent antiretroviral therapy. We exploited a predictable drug resistance mutation in the HIV reverse transcriptase to label and track cells infected during defined intervals of treatment and to identify cells replenished by ongoing replication. Decay rates of subsets of latently HIV-infected cells paradoxically decreased with time since establishment, reflecting heterogeneous lymphocyte activation and clearance. Residual low-level replication can replenish cellular reservoirs; however, it does not account for prolonged clearance rates in patients without detectable viremia. In patients receiving potent antiretroviral therapy, the latent pool has a heterogeneous and dynamic composition that comprises a progressively increasing proportion of stable lymphocytes. Eradication will not be achieved with-complete inhibition of viral replication alone.
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