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| Name | Class |
|---|---|
| Ruth M. Rothstein CORE Center | OTHER |
| Merck Sharp & Dohme LLC | INDUSTRY |
| University of North Carolina, Chapel Hill | OTHER |
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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIV monoinfection | 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 | ||
| HCV monoinfection | 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 | ||
| HIV and HCV coinfection | 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. | ||
| HIV/HCV coinfection with HCV clearance | 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) |
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| Measure | Description | Time Frame |
|---|---|---|
| Comparison of liver fibrosis with levels of inflammation and immune activation in subsets of patients with HIV, hepatitis C, and HIV and hepatitis C coinfection | Assess the associations between liver fibrosis as the dependent variable measured as a fibrosis score in kPa with predictor variables (markers of inflammation [IL-1β, IL-6, IL-8, IL10, IL-12, IL-15, IL-17, IL-21, IP10, IFN-γ, TNF-α, macrophage inflammatory protein 1 alpha (CCR7), hsCRP], immune activation and senescence [CD3, CD4, CD8, HLA DR, CD38, Ki67 CD45RA, CCR7, CD28, CD57], and tissue injury [tissue factor]) for groups b, c, and d separately by using linear regression models. Group a is the control arm for the dependent variable. | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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a) HIV monoinfected; b) hepatitis C monoinfected; c) HIV/HCV coinfected untreated for hepatitis C; and d) HIV/HCV coinfected with clearance of HCV virus. Subjects will be all matched by age and estimated duration of hepatitis C infection where applicable. In addition, subjects in strata a and c will be matched by length of ARV therapy and CD4 count first established in strata d observed immediately before the initiation of successful hepatitis C therapy or documentation of negative HCV RNA in subjects with spontaneous clearance. Subjects in strata b will be matched in the same manner to strata d, except length of ARV therapy and CD4 count variables will not be considered. All subjects with HIV infection will be on HAART with undetectable viral loads.
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| Name | Affiliation | Role |
|---|---|---|
| Gregory Huhn, MD, MPHTM | The Ruth M. Rothstein CORE Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rush University Medical Center | Chicago | Illinois | 60612 | United States | ||
| Ruth M. Rothstein CORE Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Hodowanec A, Brady KE, Gao W, Kincaid S, Plants J, Bahk M, Landay A, Huhn G. Differences in CD4+ T-cell Immune Activation in HIV, Hepatitis C (HCV), and HIV/HCV Coinfection Are Influenced by HIV and HCV Infection Status. Abstract MOPE011. 19th International AIDS Conference, Washington DC, July 23, 2012 |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D006526 | Hepatitis C |
| D005355 | Fibrosis |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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serum and plasma
| Chicago |
| Illinois |
| 60612 |
| United States |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D006525 | Hepatitis, Viral, Human |
| D018178 | Flaviviridae Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |