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

Marta E. Bull, Caroline Mitchell, Jaime Soria, Sheila Styrchak, Corey Williams-Wietzikoski, Jillian Legard, Jennifer McKernan-Mullin, Kelli Kraft, Frankline Onchiri, Joshua Stern, Sarah Holte, Kevin J. Ryan, Edward P. Acosta, Alberto La Rosa, Robert W. Coombs, Eduardo Ticona, Lisa M. Frenkel

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1389-1401
Number of pages13
JournalAIDS
Volume32
Issue number11
DOIs
StatePublished - 17 Jul 2018

Bibliographical note

Funding Information:
Source of funding: National Institutes of Health (NIH), National Institutes of Allergy and Infectious Disease grants: R01 AI071212, R01 AI091550. This publication was supported in part by the University of Washington Center for AIDS Research P30 AI027757, AI068636, and AI106701.

Publisher Copyright:
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc.

Keywords

  • CXCR4 co-receptor
  • HIV
  • HIV blips
  • HIV type-1
  • X4-viruses
  • inflammation
  • low-level viremia
  • phylogenetics

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