study on immunopathogenesis in hiv and hepatitis c coinfection

Conditions: HIV Infection; Hepatitis C Infection; Fibrosis; Inflammation

Summary: liver-related death is the leading cause of mortality in hiv-infected individuals with cd4+ cell counts over 200, and hepatitis c virus (hcv) infection is the greatest risk for liver-related mortality in hiv-positive patients. compared to hcv monoinfected individuals, patients with hiv and hcv coinfection experience accelerated progression of liver fibrosis, which can lead to higher incidence of cirrhosis, end stage liver disease (esld), and death. changes in cd8+ t-cell activation, inflammatory cytokines, and serum markers of tissue injury may offer an immunologic platform to determine factors associated with progressive liver fibrosis in coinfected patients. in this cross-sectional study we will evaluate whether hiv and hcv coinfection patients with well-controlled hiv infection who have an undetectable viral load exhibit abnormal levels of inflammation and immune activation, potentially contributing to advanced liver fibrosis. comparative groups include coinfected patients successfully treated for hepatitis c, or who have absence of hepatitis c viremia through spontaneous clearance, hepatitis c monoinfected patients, and hiv-positive patients with well-controlled hiv infection without hepatitis c. liver fibrosis will be measured by non-invasive methods. the primary objectives of this study are: 1. to determine if there are differences in markers of inflammation and immune activation in subsets of patients with hiv, hepatitis c, and hiv and hepatitis c coinfection. 2. to assess the stage of liver fibrosis using non-invasive methods in subsets of patients with hepatitis c and hiv and hepatitis c coinfection and compare the degree of liver fibrosis with levels of inflammation and immune activation.


Eligibility criteria:
inclusion criteria: * strata a (n=15): patients must be infected with hiv-1 infection without hcv. evidence should include a copy of a laboratory report of testing positive for hiv antibodies and/or hiv viral rna, and a negative antibody test for hcv * strata b (n=15): patients must be infected with hcv infection without hiv. evidence should include a copy of a laboratory report of testing positive for hcv antibodies and hcv viral rna, and a negative antibody test for hiv * strata c (n=15): patients must be co-infected with hiv \& hcv prior to enrollment. evidence should include a copy of a laboratory report of testing positive for hiv or hiv viral rna, and positive tests for hcv antibodies and hcv rna. * strata d (n=15): patients must be co-infected with hiv \& hcv prior to enrollment, with verification of successful treatment or spontaneous clearance for hepatitis c infection. evidence should include a copy of a laboratory report of testing positive for hiv or hiv viral rna, a positive tests for hcv antibodies, and undetectable hcv rna without hepatitis c treatment (spontaneous clearance) or \>6 months after hepatitis therapy (sustained virologic response) * patients should not have esld and/or hcc within 6 months of enrollment. evidence should at least include a physical examination by certified medical practitioner, negative ultrasound of the liver, and laboratory testing consistent with child a and a model for esld (meld) ≤ 10. (note: patients taking atazanavir may be enrolled with elevated total bilirubin if other child and meld criteria are normal.) * treatment with antiretroviral drugs for at least 12 months * undetectable hiv-1 rna (\<75 copies for at least 6 months) * patients must consent to study procedures * patients must be \>18 years of age exclusion criteria: * pregnancy * history of end stage liver disease * active hepatitis b infection * severe illness / discretion of investigator * bmi ≥ 35