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HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study.

ABSTRACT: In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV-chronic co-infection without anti-HCV treatment, 32 HIV patients with HCV spontaneous clearance and 29 HIV-monoinfected patients. rCD4+ T-cells were isolated and total DNA was extracted. HIV viral reservoir was measured by Alu-LTR qPCR. Differences between groups were calculated with a generalized linear model. Overall, 63.9% were men, median age of 41 years and Caucasian. Median CD4+ and CD8+ T-lymphocytes were 725 and 858 cells/mm3, respectively. CD4+ T nadir cells was 305 cells/mm3. Proviral HIV-1 DNA size was significantly increased in chronic HIV/HCV-coinfected compared to HIV-monoinfected patients (206.21?±?47.38 vs. 87.34?±?22.46, respectively; P?=?0.009), as well as in spontaneously clarified HCV co-infected patients when compared to HIV-monoinfected individuals (136.20?±?33.20; P?=?0.009). HIV-1/HCV co-infected patients showed a larger HIV-1 reservoir size in comparison to HIV-monoinfected individuals. This increase could lead to a greater complexity in the elimination of HIV-1 reservoir in HIV-1/HCV-coinfected individuals, which should be considered in the current strategies for the elimination of HIV-1 reservoir.

SUBMITTER: Lopez-Huertas MR

PROVIDER: S-EPMC6447590 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study.

López-Huertas Maria Rosa MR Palladino Claudia C Garrido-Arquero Marta M Esteban-Cartelle Beatriz B Sánchez-Carrillo Marta M Martínez-Román Paula P Martín-Carbonero Luz L Ryan Pablo P Domínguez-Domínguez Lourdes L Santos Ignacio De Los IL Moral Sara De La Fuente SF Benito José Miguel JM Rallón Norma N Alcamí José J Resino Salvador S Fernández-Rodríguez Amanda A Coiras Mayte M Briz Verónica V

Scientific reports 20190403 1

In HIV-1/HCV-coinfected patients, chronic HCV infection leads to an increased T-lymphocyte immune activation compared to HIV-monoinfected patients, thereby likely contributing to increase HIV-1 reservoir that is the major barrier for its eradication. Our objective was to evaluate the influence of HCV coinfection in HIV-1 viral reservoir size in resting (r) CD4+ T-cells (CD25-CD69-HLADR-). Multicenter cross-sectional study of 97 cART-treated HIV-1 patients, including 36 patients with HIV and HCV- ...[more]

PMID: 30944340

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Project description:Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as preferential candidates.

Dataset Information

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study.

Publications

HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study.

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