Dataset Information

Association of Hepatitis C Virus Infection With CD4/CD8 Ratio in HIV-Positive Women.

ABSTRACT:

Background

Recent studies reported that the CD4/CD8 T-cell ratio is inversely associated with biomarkers traditionally used to measure immune activation and systemic inflammation in highly active antiretroviral therapy-treated HIV-infected (HIV+) patients. The relation of hepatitis C virus (HCV) coinfection with the CD4/CD8 ratio in HIV+ patients is unknown.

Methods

We examined 50,201 CD4/CD8 ratios measured over 20 years in 3 groups of HIV+ women enrolled in the Women's Interagency HIV Study: HCV antibody negative (n = 1734), cleared HCV (n = 231), and chronic HCV (n = 751) in multivariate models. IFNL4-ΔG genotype and HCV viral load were also considered.

Results

Compared with HCV antibody negative status, chronic HCV infection was associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification (β = -0.08; P = 0.002). Cleared HCV (β = -0.10; P = 0.0009), but not IFNL4-ΔG genotype or HCV viral load, was also associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification.

Conclusions

The association of HCV coinfection with CD4/CD8 ratio is consistent with previously observed associations of HCV coinfection with biomarkers traditionally used to measure immune activation and systemic inflammation in HIV+ patients. These data provide additional support for the use of CD4/CD8 ratio for routine monitoring of immune activation and inflammation in HIV+ patients, including those with HIV/HCV coinfection; however, the unexpected association between cleared HCV and lower CD4/CD8 ratio requires additional study.

SUBMITTER: Kuniholm MH

PROVIDER: S-EPMC4874499 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:HIV infection provokes a myriad of pathological effects on the immune system where many markers of CD4+ T cell dysfunction have been identified. However, most studies to date have focused on single/double measurements of immune dysfunction, while the identification of pathological CD4+ T cell clusters that is highly associated to a specific biomarker for HIV disease remain less studied. Here, multi-parametric flow cytometry was used to investigate immune activation, exhaustion, and senescence of diverse maturation phenotypes of CD4+ T cells. The traditional method of manual data analysis was compared to a multidimensional clustering tool, FLOw Clustering with K (FLOCK) in two cohorts of 47 untreated HIV-infected individuals and 21 age and sex matched healthy controls. In order to reduce the subjectivity of FLOCK, we developed an "artificial reference", using 2% of all CD4+ gated T cells from each of the HIV-infected individuals. Principle component analyses demonstrated that using an artificial reference lead to a better separation of the HIV-infected individuals from the healthy controls as compared to using a single HIV-infected subject as a reference or analyzing data manually. Multiple correlation analyses between laboratory parameters and pathological CD4+ clusters revealed that the CD4/CD8 ratio was the preeminent surrogate marker of CD4+ T cells dysfunction using all three methods. Increased frequencies of an early-differentiated CD4+ T cell cluster with high CD38, HLA-DR and PD-1 expression were best correlated (Rho = -0.80, P value = 1.96×10-11) with HIV disease progression as measured by the CD4/CD8 ratio. The novel approach described here can be used to identify cell clusters that distinguish healthy from HIV infected subjects and is biologically relevant for HIV disease progression. These results further emphasize that a simple measurement of the CD4/CD8 ratio is a useful biomarker for assessment of combined CD4+ T cell dysfunction in chronic HIV disease.