Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals.
AIDS
; 31(10): 1405-1414, 2017 06 19.
Article
em En
| MEDLINE
| ID: mdl-28358734
ABSTRACT
OBJECTIVE:
To assess if the reduction in HIV-1 RNA in CD4 T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART).DESIGN:
Clinical trial (NCT01285050).METHODS:
Next-generation sequencing was used to study total RNA from activated CD4 T cells (CD38 and human leukocyte antigen - antigen D related (HLA-DR) expressing) collected from 19 treatment-naïve HIV-1/hepatitis C virus-infected patients before and early after ART initiation (≥12 weeks after plasma HIV-1 RNA <50 copies/ml). To validate comparisons, pre and post-ART measures were adjusted for input RNA and overall read number.RESULTS:
As expected, ART use was associated with a median [interquartile range (IQR)] 4.3% (2.2-8.3) reduction in the proportion of activated CD4 T cells (Pâ=â0.0008). Whereas in those activated CD4 T cells no consistent differences in overall gene expression were detected, interferon-stimulated gene expression declined (Pâ<â2â×â10). Pre-ART, sorted activated CD4 T cells contained a median (IQR) of 959 (252-1614) HIV-1 reads/10 reads compared with 72 (55-152) HIV-1 reads/10 reads after at least 12 weeks of suppressive ART (Pâ=â8â×â10). The decrease in HIV-1 reads in activated CD4 T cells was associated with the change in plasma HIV-1 RNA levels (râ=â0.77, Pâ=â2â×â10) and the change in the proportion of activated CD4 T cells (râ=â0.70, Pâ=â0.0016).CONCLUSION:
Months of ART led to a marked decrease in cell-associated HIV-1 RNA and interferon-stimulated genes expression in activated CD4 T cells that were strongly associated with the reduction in the proportion of activated CD4 T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Viral
/
Ativação Linfocitária
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Linfócitos T CD4-Positivos
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Infecções por HIV
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HIV-1
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Female
/
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article