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Impact of highly active antiretroviral therapy and immunologic status on hepatitis C virus quasispecies diversity in human immunodeficiency virus/hepatitis C virus-coinfected patients.

ABSTRACT: This study analyzes the effect of highly active antiretroviral therapy (HAART), and thus immunologic status, on hepatitis C virus (HCV) load and quasispecies diversity in patients coinfected with the human immunodeficiency virus (HIV) and HCV. Three cohorts of coinfected patients were analyzed retrospectively over a period of 7 to 10 months: group A was antiretroviral drug naïve at baseline and then on HAART for the remainder of the study, group B did not receive antiretroviral therapy at any point, and group C was on HAART for the entire study. HCV quasispecies diversity was analyzed by sequencing hypervariable region 1. In a longitudinal analysis, there was no significant change from baseline in any immunologic, virologic, or quasispecies parameter in any of the three groups. However, in comparison to groups A and B, group C had significantly higher CD4+- and CD8+-cell counts, a trend toward a higher HCV load, and significantly increased number of HCV clones, entropy, genetic distance, and ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site (Ka/Ks). In addition, CD4+-cell count was positively correlated with HCV load, genetic distance, and Ka. Interestingly, patients infected with HCV genotype 2 or 3 had a significantly higher CD4+-cell count, HCV load, genetic distance, and Ka/Ks than those infected with genotype 1. These results suggest that there is no immediate effect of HAART on HCV but that, with prolonged HAART, immune restoration results in an increase in HCV load and quasispecies diversity.

SUBMITTER: Babik JM

PROVIDER: S-EPMC140862 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature

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Impact of highly active antiretroviral therapy and immunologic status on hepatitis C virus quasispecies diversity in human immunodeficiency virus/hepatitis C virus-coinfected patients.

Babik Jennifer M JM Holodniy Mark M

Journal of virology 20030201 3

This study analyzes the effect of highly active antiretroviral therapy (HAART), and thus immunologic status, on hepatitis C virus (HCV) load and quasispecies diversity in patients coinfected with the human immunodeficiency virus (HIV) and HCV. Three cohorts of coinfected patients were analyzed retrospectively over a period of 7 to 10 months: group A was antiretroviral drug naïve at baseline and then on HAART for the remainder of the study, group B did not receive antiretroviral therapy at any po ...[more]

PMID: 12525628

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Project description:Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have higher levels of immune activation, impaired antigen-specific responses, and accelerated fibrogenesis compared to patients monoinfected with HCV. Whether different direct-acting antiviral (DAA) combinations have differential effects on immunophenotypes and functions following successful HCV therapy remain unknown. Therefore, we aimed to assess the peripheral T-cell immunophenotypes and functions in patients coinfected with HIV/HCV who were successfully treated with combination DAA treatment regimens. We analyzed peripheral blood mononuclear cells (PBMCs) at baseline and at the time of sustained viral response (SVR) from subjects treated with three different combination DAA regimens: daclatasvir (DCV) and asunaprevir (ASV) for 24 weeks (CONQUER 2-DAA), DCV/ASV/beclabuvir (BCV) for 12 weeks (CONQUER 3-DAA), and sofosbuvir (SOF) and ledipasvir (LDV) for 12 weeks (ERADICATE study). We used flow cytometry to assess T-cell phenotypes (activation and exhaustion) and HCV-specific T-cell functions (cytokine secretion and cytotoxicity). Statistical analyses were conducted using the Wilcoxon matched-pairs signed-rank test with P < 0.05 considered significant. Overall, there was an improvement in T-cell exhaustion markers, a decrease in T-cell activation, an increase in the effector memory population, and improved T-cell function after achieving SVR, with the largest effects noted with CONQUER 3-DAA treatment. Conclusion: Treatment with DCV/ASV/BCV in patients coinfected with HIV/HCV resulted in greater restoration of the T-cell impairments and perturbations associated with HIV/HCV coinfection to an extent that was greater than that observed in either two-drug regimens. We showed that different DAA-based therapies have different immunologic outcomes after successful HCV treatment in patients coinfected with HIV/HCV. This information will be beneficial for providers when selecting the regimens for patients coinfected with HIV/HCV.

Dataset Information

Impact of highly active antiretroviral therapy and immunologic status on hepatitis C virus quasispecies diversity in human immunodeficiency virus/hepatitis C virus-coinfected patients.

Publications

Impact of highly active antiretroviral therapy and immunologic status on hepatitis C virus quasispecies diversity in human immunodeficiency virus/hepatitis C virus-coinfected patients.

Similar Datasets

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