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Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal disorder.

ABSTRACT: Both hepatitis C virus (HCV) and human immunodeficiency virus (HIV) penetrate the central nervous system. HIV-associated neuroretinal disorder (HIV-NRD), a visual impairment of reduced contrast sensitivity and reading ability, is associated with cytokine dysregulation and genetic polymorphisms in the anti-inflammatory interleukin 10 (IL-10) signaling pathway. We investigated associations between HCV and HIV-NRD and between HCV and single-nucleotide polymorphisms (SNPs) in the IL-10 receptor 1 (IL10R1) gene.Logistic and Cox regression analysis were used to analyze risk factors for HIV-NRD in 1576 HIV-positive patients who did not have an ocular opportunistic infection at enrollment. Median follow-up was 4.9 years (interquartile range, 2.4-8.8 years). Four IL10R1 SNPs were examined in a subset of 902 patients.The group included 290 patients with chronic HCV infection, 74 with prior infection, and 1212 with no HCV markers. There were 244 prevalent cases of HIV-NRD and 263 incident cases (rate = 3.9/100 person-years). In models adjusted for demographics, HIV treatment and status, liver function, and immune status, both the prevalence and incidence of HIV-NRD were significantly higher in patients with chronic HCV infection (odds ratio = 1.54; 95% confidence interval [CI], 1.03-2.31 and hazard ratio = 1.62; 95% CI, 1.13-2.34, respectively), compared to patients with no HCV markers. Chronic HCV was associated with rs2228055 and 2 additional IL-10R1 SNPs expected to reduce IL-10 signaling. HIV-NRD was not significantly associated with these SNPs.HCV is a possible risk factor for HIV-NRD. Genetic analysis suggests that alterations in the IL-10 signaling pathway may increase susceptibility to HIV-NRD and HCV infection. Inflammation may link HCV and HIV-NRD.

SUBMITTER: Branch AD

PROVIDER: S-EPMC3814824 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal disorder.

Branch Andrea D AD Drye Lea T LT Van Natta Mark L ML Sezgin Efe E Fishman Sarah L SL Dieterich Douglas T DT Meinert Curtis L CL Jabs Douglas A DA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20130930 11

<h4>Background</h4>Both hepatitis C virus (HCV) and human immunodeficiency virus (HIV) penetrate the central nervous system. HIV-associated neuroretinal disorder (HIV-NRD), a visual impairment of reduced contrast sensitivity and reading ability, is associated with cytokine dysregulation and genetic polymorphisms in the anti-inflammatory interleukin 10 (IL-10) signaling pathway. We investigated associations between HCV and HIV-NRD and between HCV and single-nucleotide polymorphisms (SNPs) in the ...[more]

PMID: 24081683

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Project description:PurposePatients with AIDS have an abnormality of retina/optic nerve function, manifested as decreased contrast sensitivity (in the absence of ocular opportunistic infections or media opacity), abnormalities on automated perimetry, and loss of retinal nerve fiber layer, even among those with good visual acuity, termed the "human immunodeficiency virus (HIV) neuroretinal disorder." The objectives of this study were to determine the prevalence, incidence, risk factors, and outcomes of HIV neuroretinal disorder.DesignProspective cohort study.ParticipantsA total of 1822 patients with AIDS without ocular infections or media opacities.MethodsPatients with HIV neuroretinal disorder were identified by a contrast sensitivity <1.50 log units in either eye in the absence of ocular opportunistic infections or media opacity.Main outcome measuresIncidence of HIV neuroretinal disorder, mortality, visual impairment (visual acuity ≤20/50), and blindness (≤20/200) on logarithmic visual acuity charts.ResultsSixteen percent of participants had HIV neuroretinal disorder at enrollment. The estimated cumulative incidence by 20 years after AIDS diagnosis was 51% (95% confidence interval [CI], 46-55). Human immunodeficiency virus neuroretinal disorder was more common in women and African Americans. Risk factors for HIV neuroretinal disorder included hepatitis C infection, low CD4+ T cells, and detectable HIV RNA in the blood. Patients with HIV neuroretinal disorder had a 70% excess mortality versus those without it, even after adjusting for CD4+ T cells and HIV load (hazard ratio [HR], 1.7; 95% CI, 1.3-2.1; P < 0.0001). Patients with HIV neuroretinal disorder had increased risks of bilateral visual impairment (HR, 6.5; 95% CI, 2.6-10.6; P < 0.0001) and blindness (HR, 5.9; 95% CI, 2.8-13.7; P = 0.01) versus those without HIV neuroretinal disorder.ConclusionsHuman immunodeficiency virus neuroretinal disorder is a common finding among patients with AIDS, and it is associated with an increased mortality and an increased risk of visual impairment. Successful antiretroviral therapy decreases but does not eliminate the risk of HIV neuroretinal disorder.

Project description:Hepatitis C virus (HCV) infection has been associated with reduced bone mineral density, but its association with fracture rates is unknown, particularly in the setting of human immunodeficiency virus (HIV) coinfection. Our aims were to determine whether persons with HCV infection alone are at increased risk for hip fracture, compared to uninfected individuals, and to examine whether the risk of hip fracture is higher among HCV/HIV-coinfected persons, compared to those with HCV alone, those with HIV alone, and those uninfected with either virus. We conducted a cohort study in 36,950 HCV/HIV-coinfected, 276,901 HCV-monoinfected, 95,827 HIV-monoinfected, and 3,110,904 HCV/HIV-uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999-2005). Incidence rates of hip fracture were lowest among uninfected persons (1.29 events/1,000 person-years), increased with the presence of either HIV infection (1.95 events/1,000 person-years) or HCV infection (2.69 events/1,000 person-years), and were highest among HCV/HIV-coinfected individuals (3.06 events/1,000 person-years). HCV/HIV coinfection was associated with an increased relative hazard (adjusted hazard ratio [HR] [95% confidence interval; CI]) of hip fracture, compared to HCV-monoinfected (HR, 1.38; 95% CI: 1.25-1.53), HIV-monoinfected (females: HR, 1.76; 95% CI: 1.44-2.16; males: HR, 1.36; 95% CI: 1.20-1.55), and HCV/HIV-uninfected persons (females: HR, 2.65; 95% CI: 2.21-3.17; males: HR, 2.20; 95% CI: 1.97-2.47). HCV monoinfection was associated with an increased risk of hip fracture, compared to uninfected individuals, and the relative increase was highest in the youngest age groups (females, 18-39 years: HR, 3.56; 95% CI: 2.93-4.32; males, 18-39 years: HR, 2.40; 95% CI: 2.02-2.84).Among Medicaid enrollees, HCV/HIV coinfection was associated with increased rates of hip fracture, compared to HCV-monoinfected, HIV-monoinfected, and HCV/HIV-uninfected persons. HCV-monoinfected patients had an increased risk of hip fracture, compared to uninfected individuals.

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Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal disorder.

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Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal disorder.

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