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PMID: 10516049 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Evolution of envelope sequences of human immunodeficiency virus type 1 in cellular reservoirs in the setting of potent antiviral therapy.

Journal of virology ·Vol. 73 ·No. 11 ·1999-11-00 ·Pages 9404-12

Günthard HF, Frost SD, Leigh-Brown AJ, Ignacio CC, Kee K, Perelson AS, Spina CA, Havlir DV, Hezareh M, Looney DJ, Richman DD, Wong JK

Abstract

In human immunodeficiency virus (HIV)-infected patients treated with potent antiretroviral therapy, the persistence of latently infected cells may reflect the long decay half-life of this cellular reservoir or ongoing viral replication at low levels with continuous replenishment of the population or both. To address these possibilities, sequences encompassing the C2 and V3 domains of HIV-1 env were analyzed from virus present in baseline plasma and from viral isolates obtained after 2 years of suppressive therapy in six patients. The presence of sequence changes consistent with evolution was demonstrated for three subjects and correlated with less complete suppression of viral replication, as indicated by the rapidity of the initial virus load decline or the intermittent reappearance of even low levels of detectable viremia. Together, these results provide evidence for ongoing replication. In the remaining three patients, virus recovered after 2 years of therapy was either genotypically contemporary with or ancestral to virus present in plasma 2 years before, indicating that virus recovery had indeed resulted from activation of latently infected cells.

MeSH Terms
Amino Acid Sequence Anti-HIV Agents/therapeutic use Cloning, Molecular Drug Therapy, Combination Evolution, Molecular HIV Envelope Protein gp120/chemistry,genetics HIV Infections/drug therapy,virology HIV-1/genetics,physiology Humans Leukocytes, Mononuclear/virology Molecular Sequence Data Phylogeny RNA, Viral/blood Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Viral Load Virus Latency Virus Replication
Chemicals
Anti-HIV Agents HIV Envelope Protein gp120 RNA, Viral
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Günthard H F
University of California, San Diego, USA.
Frost S D
Leigh-Brown A J
Ignacio C C
Kee K
Perelson A S
Spina C A
Havlir D V
Hezareh M
Looney D J
Richman D D
Wong J K
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.11.9404-9412.1999
Published
1999-11-00
Pages
9404-12
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC112975
Subset
IM
Grants
NIAID NIH HHS · AI 27670 · United States
NIAID NIH HHS · R01 AI043752 · United States
NIAID NIH HHS · U01 AI027670 · United States
NIAID NIH HHS · R37 AI029164 · United States
NCRR NIH HHS · R01 RR006555 · United States
NIAID NIH HHS · U01 AI038858 · United States
NIAID NIH HHS · P30 AI036214 · United States
NIAID NIH HHS · AI 43752 · United States
NIAID NIH HHS · AI 01361 · United States
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External Links
PubMed source DOI: 10.1128/JVI.73.11.9404-9412.1999 PMC Full Text View journal details
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