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Persistence of viral reservoirs in multiple tissues after antiretroviral therapy suppression in a macaque RT-SHIV model

Kline, C and Ndjomou, J and Franks, T and Kiser, R and Coalter, V and Smedley, J and Piatak, M and Mellors, JW and D Lifson, J and Ambrose, Z (2013) Persistence of viral reservoirs in multiple tissues after antiretroviral therapy suppression in a macaque RT-SHIV model. PLoS ONE, 8 (12).

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Abstract

Although antiretroviral therapy (ART) can suppress HIV-1 replication sufficiently to eliminate measurable plasma viremia, infected cells remain and ensure viral recrudescence after discontinuation of ART. We used a macaque model of HIV-1/AIDS to evaluate the location of infected cells during ART. Twelve macaques were infected with RT-SHIVmne, a SIV containing HIV-1 reverse transcriptase, conferring sensitivity to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ten to fourteen weeks post-infection, 6 animals were treated with 3 or 4 antiretroviral drugs for 17-20 weeks; 6 control animals remained untreated. Viral DNA (vDNA) and RNA (vRNA) were measured in peripheral blood mononuclear cells (PBMC) and at necropsy in multiple tissues by quantitative PCR and RT-PCR. The majority of virally infected cells were located in lymphoid tissues with variable levels in the gastrointestinal tract of both treated and untreated animals. Tissue viral DNA levels correlated with week 1 plasma viremia, suggesting that tissues that harbor proviral DNA are established within the first week of infection. PBMC vDNA levels did not correlate with plasma viremia or tissue levels of vDNA. vRNA levels were high in lymphoid and gastrointestinal tissues of the untreated animals; animals on ART had little vRNA expressed in tissues and virus could not be cultured from lymph node resting CD4+ cells after 17-20 weeks on ART, indicating little or no ongoing viral replication. Strategies for eradication of HIV-1 will need to target residual virus in ART suppressed individuals, which may not be accurately reflected by frequencies of infected cells in blood. © 2013 Kline et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kline, Ccjk14@pitt.eduCJK14
Ndjomou, J
Franks, T
Kiser, R
Coalter, V
Smedley, J
Piatak, M
Mellors, JWjwm1@pitt.eduJWM1
D Lifson, J
Ambrose, Zzaa4@pitt.eduZAA4
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorMattapallil, Joseph JUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 18 December 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0084275
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Date Deposited: 16 Jun 2014 16:36
Last Modified: 26 Feb 2019 19:55
URI: http://d-scholarship.pitt.edu/id/eprint/21855

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