Heterogeneous Clearance Rates of Long-Lived Lymphocytes Infected with HIV: Intrinsic Stability Predicts Lifelong Persistence
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 de...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 8; pp. 4819 - 4824 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
15.04.2003
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved February 12, 2003 To whom correspondence should be addressed. E-mail: j2wong@ucsd.edu. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0736332100 |