Document Detail


Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.
MedLine Citation:
PMID:  23014521     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Interest in targeting HIV reservoirs is fueling trials that may decrease reservoir size and/or induce viral replication. Therefore, we aimed to develop strategies to sensitively measure changes in these parameters in patients on and off antiretroviral therapy (ART). Achieving these goals may help evaluate the effects of future clinical trials.
DESIGN: To determine the relationship between measurements of total and integrated HIV DNA and their role as markers of reservoir size and ongoing replication, these parameters were measured during the first year of ART, during long-term effective ART, and during a clinical trial aimed at targeting reservoirs.
METHODS: Total and integrated HIV DNA were measured in patient samples using quantitative PCR techniques. CD4(+)T cell counts and plasma viremia were also monitored.
RESULTS: Unintegrated HIV DNA became undetectable during the first year of ART. Total and integrated HIV DNA levels were generally equal in well controlled patients on ART, and low-level plasma viremia correlated best with integration measures. Finally, patients who controlled plasma viremia (<400 copies/ml) during interferon-α monotherapy exhibited a decrease in the level of integrated but not total HIV DNA and a rise in the ratio of total to integrated HIV DNA over time.
CONCLUSION: Our findings suggest that appearance of unintegrated HIV DNA reflects residual HIV expression and de-novo reverse transcription, providing insight into the mechanism by which interferon-α reduces the HIV reservoir. We conclude that concurrent measurements of total and integrated HIV DNA provide information regarding reservoir size and ongoing replication in trials targeting HIV.
Authors:
Angela M Mexas; Erin H Graf; Matthew J Pace; Jianqing J Yu; Emmanouil Papasavvas; Livio Azzoni; Michael P Busch; Michele Di Mascio; Andrea S Foulkes; Stephen A Migueles; Luis J Montaner; Una O'Doherty
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  26     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-06-03     Revised Date:  2014-05-26    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  2295-306     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / pharmacology*,  therapeutic use
Biological Markers / metabolism
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes / drug effects
Clinical Trials as Topic
DNA, Viral / drug effects*
Disease Reservoirs / virology
Female
HIV Infections / drug therapy*
HIV-1 / drug effects*,  genetics*
Humans
Interferon-alpha / pharmacology*,  therapeutic use
Male
Middle Aged
Polymerase Chain Reaction
Viral Load / drug effects
Viremia / virology
Virus Integration / drug effects
Virus Replication / drug effects
Grant Support
ID/Acronym/Agency:
5K08AI073102/AI/NIAID NIH HHS; K02 AI078766/AI/NIAID NIH HHS; K02AI078766/AI/NIAID NIH HHS; K08 AI073102/AI/NIAID NIH HHS; P30 AI 045008/AI/NIAID NIH HHS; P30 CA10815/CA/NCI NIH HHS; R21 AI087461/AI/NIAID NIH HHS; R21 AI087461/AI/NIAID NIH HHS; T32 AI007632/AI/NIAID NIH HHS; U01 AI065279/AI/NIAID NIH HHS; U01AI065279/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Biological Markers; 0/DNA, Viral; 0/Interferon-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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