RESUMO
OBJECTIVE: During effective antiretroviral therapy (ART), low-level plasma viremias (LLV) (HIV RNA >30-1000âcopies/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 30âcopies/ml, LLV were detected in 33 of 82 (40%), with a LLV median HIV RNA of 73âcopies/ml. Participants with vs. without LLV had significantly higher pre-ART plasma HIV RNA (Pâ<â0.001) and PBMC HIV DNA (Pâ<â0.007); 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 (Pâ=â0.004) and LLV with more X4 variants (Pâ=â0.02). 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.
Assuntos
Antirretrovirais/uso terapêutico , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV/classificação , HIV/genética , Viremia/tratamento farmacológico , DNA Viral/sangue , HIV/isolamento & purificação , Humanos , Leucócitos Mononucleares/virologia , Peru , Filogenia , Plasma/virologia , Estudos Prospectivos , RNA Viral/sangue , Análise de Sequência de DNA , Viremia/virologiaRESUMO
OBJECTIVE: Inflammatory biomarkers associated with cardiovascular disease are elevated in HIV-infected persons. These biomarkers improve with antiretroviral therapy (ART) but do not normalize to values observed in HIV-uninfected adults. Little is known regarding biomarkers of inflammation in HIV-infected Peruvians, in whom an increased burden of infectious diseases may exacerbate inflammation, and women, in whom sex difference may alter inflammation compared with men. METHODS: Peruvians initiating first-line ART were enrolled in a prospective observational study. Individuals with suppression of HIV RNA plasma loads to less than 30âcopies/ml when determined quarterly over 24 months of ART, had biomarkers of inflammation and cellular activation measured pre-ART and at 24-months of ART, and evaluated for associations with sex and clinical parameters. RESULTS: Pre-ART high-sensitivity C-reactive protein (hsCRP) values of men were in the high-risk cardiovascular disease category (>3.0âmg/l) more frequently compared with women (Pâ=â0.02); most women's values were in the low/average-risk categories. At 24 months of suppressive ART, hsCRP concentrations decreased in men (Pâ=â0.03), but tended to increase in women, such that the proportion with high-risk hsCRP did not differ by sex. Pre-ART, soluble CD163 concentrations were higher in women compared with men (Pâ=â0.02), and remained higher after 24 months of suppressive ART (Pâ=â0.02). All other inflammatory biomarkers (Pâ<â0.03) decreased across sexes. Biomarker concentrations were not associated with BMI or coinfections. CONCLUSION: Elevated inflammatory biomarkers persisted despite 24 months of suppressive ART in a subset of Peruvians, and to a greater extent in women compared with men. These findings suggest that lifestyle or pharmacologic interventions may be required to optimize the health of HIV-infected Peruvians, particularly women.