Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation. (17th July 2018)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: AIDS. Volume 32:Number 11(2018)
• Publication Date: 2018-07-17
• Subjects: CXCR4 co-receptor -- HIV -- HIV blips -- HIV type-1 -- inflammation -- low-level viremia -- phylogenetics -- X4-viruses; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001824
• Languages: English
• ISSNs: 0269-9370

Abstract

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. Abstract : Supplemental Digital Content is available in the text