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Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation

OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30–1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expande...

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Autores principales: Bull, Marta E., Mitchell, Caroline, Soria, Jaime, Styrchak, Sheila, Williams-Wietzikoski, Corey, Legard, Jillian, McKernan-Mullin, Jennifer, Kraft, Kelli, Onchiri, Frankline, Stern, Joshua, Holte, Sarah, Ryan, Kevin J., Acosta, Edward P., La Rosa, Alberto, Coombs, Robert W., Ticona, Eduardo, Frenkel, Lisa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039404/
https://www.ncbi.nlm.nih.gov/pubmed/29683841
http://dx.doi.org/10.1097/QAD.0000000000001824
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author Bull, Marta E.
Mitchell, Caroline
Soria, Jaime
Styrchak, Sheila
Williams-Wietzikoski, Corey
Legard, Jillian
McKernan-Mullin, Jennifer
Kraft, Kelli
Onchiri, Frankline
Stern, Joshua
Holte, Sarah
Ryan, Kevin J.
Acosta, Edward P.
La Rosa, Alberto
Coombs, Robert W.
Ticona, Eduardo
Frenkel, Lisa M.
author_facet Bull, Marta E.
Mitchell, Caroline
Soria, Jaime
Styrchak, Sheila
Williams-Wietzikoski, Corey
Legard, Jillian
McKernan-Mullin, Jennifer
Kraft, Kelli
Onchiri, Frankline
Stern, Joshua
Holte, Sarah
Ryan, Kevin J.
Acosta, Edward P.
La Rosa, Alberto
Coombs, Robert W.
Ticona, Eduardo
Frenkel, Lisa M.
author_sort Bull, Marta E.
collection PubMed
description OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30–1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naive Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed. Inflammatory biomarker concentrations were measured pre and during ART. Single-genome amplification (SGA) derived HIV env and pol genotypes from pre-ART and LLV specimens. Antiretroviral levels during ART assessed adherence. Statistical associations and phylogenetic relationships were examined. RESULTS: Among 82 participants with median plasma HIV RNA less than 30 copies/ml, LLV were detected in 33 of 82 (40%), with a LLV median HIV RNA of 73 copies/ml. Participants with vs. without LLV had significantly higher pre-ART plasma HIV RNA (P < 0.001) and PBMC HIV DNA (P < 0.007); but, during ART, their antiretroviral drug levels were similar. LLV env sequences were monotypic in 17 of 28 (61%) and diverse in 11 of 28 (39%) participants. Those with the monotypic vs. diverse LLV pattern had elevated hsCRP and sCD163 (P = 0.004) and LLV with more X4 variants (P = 0.02). CONCLUSION: In individuals with monotypic LLV sequences, higher levels of pre-ART HIV DNA and RNA, systemic inflammation and X4 viruses suggest an interaction between inflammation and the production of virions from proliferating infected cells, and that naïve T cells may be a source of LLV.
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spelling pubmed-60394042018-07-20 Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation Bull, Marta E. Mitchell, Caroline Soria, Jaime Styrchak, Sheila Williams-Wietzikoski, Corey Legard, Jillian McKernan-Mullin, Jennifer Kraft, Kelli Onchiri, Frankline Stern, Joshua Holte, Sarah Ryan, Kevin J. Acosta, Edward P. La Rosa, Alberto Coombs, Robert W. Ticona, Eduardo Frenkel, Lisa M. AIDS Basic Science OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30–1000 copies/ml) can be detected intermittently. We hypothesized that systemic inflammation is associated with LLV either as the cause or result of the production of virions from clonally expanded cells. METHODS: Prospective cohort study of HIV-infected ART-naive Peruvians enrolled prior to ART and followed for 2 years. Plasma HIV RNA and peripheral blood mononuclear cell (PBMC) HIV DNA concentrations were quantified pre-ART from individuals whose plasma HIV RNA was ART-suppressed. Inflammatory biomarker concentrations were measured pre and during ART. Single-genome amplification (SGA) derived HIV env and pol genotypes from pre-ART and LLV specimens. Antiretroviral levels during ART assessed adherence. Statistical associations and phylogenetic relationships were examined. RESULTS: Among 82 participants with median plasma HIV RNA less than 30 copies/ml, LLV were detected in 33 of 82 (40%), with a LLV median HIV RNA of 73 copies/ml. Participants with vs. without LLV had significantly higher pre-ART plasma HIV RNA (P < 0.001) and PBMC HIV DNA (P < 0.007); but, during ART, their antiretroviral drug levels were similar. LLV env sequences were monotypic in 17 of 28 (61%) and diverse in 11 of 28 (39%) participants. Those with the monotypic vs. diverse LLV pattern had elevated hsCRP and sCD163 (P = 0.004) and LLV with more X4 variants (P = 0.02). CONCLUSION: In individuals with monotypic LLV sequences, higher levels of pre-ART HIV DNA and RNA, systemic inflammation and X4 viruses suggest an interaction between inflammation and the production of virions from proliferating infected cells, and that naïve T cells may be a source of LLV. Lippincott Williams & Wilkins 2018-07-17 2018-07-02 /pmc/articles/PMC6039404/ /pubmed/29683841 http://dx.doi.org/10.1097/QAD.0000000000001824 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0
spellingShingle Basic Science
Bull, Marta E.
Mitchell, Caroline
Soria, Jaime
Styrchak, Sheila
Williams-Wietzikoski, Corey
Legard, Jillian
McKernan-Mullin, Jennifer
Kraft, Kelli
Onchiri, Frankline
Stern, Joshua
Holte, Sarah
Ryan, Kevin J.
Acosta, Edward P.
La Rosa, Alberto
Coombs, Robert W.
Ticona, Eduardo
Frenkel, Lisa M.
Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation
title Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation
title_full Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation
title_fullStr Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation
title_full_unstemmed Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation
title_short Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation
title_sort monotypic low-level hiv viremias during antiretroviral therapy are associated with disproportionate production of x4 virions and systemic immune activation
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039404/
https://www.ncbi.nlm.nih.gov/pubmed/29683841
http://dx.doi.org/10.1097/QAD.0000000000001824
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