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Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation.
- Source :
-
AIDS (London, England) [AIDS] 2018 Jul 17; Vol. 32 (11), pp. 1389-1401. - Publication Year :
- 2018
-
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.<br />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.<br />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).<br />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.
- Subjects :
- DNA, Viral blood
HIV isolation & purification
Humans
Leukocytes, Mononuclear virology
Peru
Phylogeny
Plasma virology
Prospective Studies
RNA, Viral blood
Sequence Analysis, DNA
Viremia virology
Anti-Retroviral Agents therapeutic use
Genotype
HIV classification
HIV genetics
HIV Infections drug therapy
HIV Infections virology
Viremia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5571
- Volume :
- 32
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- AIDS (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 29683841
- Full Text :
- https://doi.org/10.1097/QAD.0000000000001824