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Lack of Detectable HIV-1 Molecular Evolution during Suppressive Antiretroviral Therapy

Kearney, MF and Spindler, J and Shao, W and Yu, S and Anderson, EM and O'Shea, A and Rehm, C and Poethke, C and Kovacs, N and Mellors, JW and Coffin, JM and Maldarelli, F (2014) Lack of Detectable HIV-1 Molecular Evolution during Suppressive Antiretroviral Therapy. PLoS Pathogens, 10 (3). ISSN 1553-7366

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Abstract

A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed HIV-1 genetic variation and divergence in patients' plasma before cART, during suppression on cART, and after viral rebound. Single-genome sequences of plasma HIV-1 RNA were obtained from HIV-1 infected patients prior to cART (N = 14), during suppression on cART (N = 14) and/or after viral rebound following interruption of cART (N = 5). Intra-patient population diversity was measured by average pairwise difference (APD). Population structure was assessed by phylogenetic analyses and a test for panmixia. Measurements of intra-population diversity revealed no significant loss of overall genetic variation in patients treated for up to 15 years with cART. A test for panmixia, however, showed significant changes in population structure in 2/10 patients after short-term cART (<1 year) and in 7/10 patients after long-term cART (1-15 years). The changes consisted of diverse sets of viral variants prior to cART shifting to populations containing one or more genetically uniform subpopulations during cART. Despite these significant changes in population structure, rebound virus after long-term cART had little divergence from pretherapy virus, implicating long-lived cells infected before cART as the source for rebound virus. The appearance of genetically uniform virus populations and the lack of divergence after prolonged cART and cART interruption provide strong evidence that HIV-1 persists in long-lived cells infected before cART was initiated, that some of these infected cells may be capable of proliferation, and that on-going cycles of viral replication are not evident.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kearney, MF
Spindler, J
Shao, W
Yu, S
Anderson, EM
O'Shea, A
Rehm, C
Poethke, C
Kovacs, N
Mellors, JWjwm1@pitt.eduJWM1
Coffin, JM
Maldarelli, F
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSiliciano, Robert F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 10
Number: 3
DOI or Unique Handle: 10.1371/journal.ppat.1004010
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
ISSN: 1553-7366
Date Deposited: 01 Jul 2014 16:32
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/22127

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