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Sponsored by: |
Bayside Health |
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Information provided by: | Bayside Health |
ClinicalTrials.gov Identifier: | NCT00164060 |
The purpose of this study is to examine the effect of GB virus C (GBV-C) on the natural history of chronic hepatitis C virus (HCV) infection in subjects co-infected with HIV and HCV. The other aspect of the study is to assess the effect of GBV-C on the severity of liver disease due to chronic hepatitis C in subjects co-infected with HIV and HCV. This will be done by determining the point prevalence of co-infection retrospectively then following that cohort prospectively. In addition, further individuals will be recruited in a prospective manner.
Condition |
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Hepatitis C HIV Infections |
Study Type: | Observational |
Study Design: | Natural History, Longitudinal, Defined Population, Retrospective Study |
Official Title: | Associations, Outcomes and Genomics of GB Virus C, Hepatitis C Virus and Human Immunodeficiency Virus Infection |
Estimated Enrollment: | 200 |
Study Start Date: | February 2004 |
Estimated Study Completion Date: | May 2007 |
Background and Research Plan:
GBV-C and hepatitis G virus (HGV) are both RNA viruses from the Flaviviridae family. Molecular characterization of these viruses has shown them to be virtually identical to each other (1,2). GBV-C was first isolated in 1995 from an archival blood sample obtained in the 1960s from a surgeon with acute non A-E hepatitis (3). GBV-C has a 29% amino acid sequence homology with Hepatitis C Virus (HCV), another flavivirus (4). However, GBV-C in contrast to HCV, is not hepatotropic as the virus neither replicates primarily in hepatocytes nor causes acute or chronic hepatitis. Indeed, GBV-C does not cause any specific disease nor does it represent a substantial health risk in humans. Nevertheless, GBV-C infection is relatively common with a 2% prevalence rate in healthy blood donors, the majority of whom clear the virus and develop antibodies to the envelope glycoprotein E2.
HIV infection has a particularly high rate of co-infection with GBV-C. Studies suggest that co-infection leads to a beneficial effect on the course of HIV (5,6,7) with co-infection associated with a significantly lower mortality rate among HIV-infected subjects compared to those not infected with GBV-C.
The mechanism of the beneficial effect of GBV-C on the course of HIV infection is obscure.
Among new cases of non-A, non-B hepatitis in the United States, 18 percent are positive for GBV-C, and 80% of these patients are also infected with HCV.
Amongst patients with HCV, 10-20% have GBV-C RNA in their serum (4). In another report 189 patients with chronic HCV infection were evaluated; 21 (11%) were positive for GBV-C RNA (8). The course of the HCV infection and the response to interferon-alfa were not affected by co-infection with GBV-C.
Interferon-alfa led to a decrease in GBV-C RNA titers that was not sustained after the cessation of therapy. Similar findings were noted in another study in which liver biopsies were performed (9). Detailed histopathologic examination revealed no difference between the patients infected with HCV alone and the 15 percent who were co-infected with GBV-C. There have been no studies to date looking at the effect GBV-C, HCV and HIV have on each other.
Our previous studies into HIV and GBV-C have suggested that co-infection is common. Active GBV-C infection is frequently observed in persons involved in high-risk sexual activity and with HIV infection. Homosexual intercourse appears to be a more effective means of transmission of GBV-C. GBV-C has the same epidemiology and transmission as HIV and underlines the intimate association between GBV-C and HIV (10).
Methods/Experimental Design:
Stored sera is available from people who have attended the Hepatitis and HIV clinics at the Alfred Hospital. Sera is available back to approximately 1990 and has been stored at minus 20ºC and as such is suitable for GBV-C detection particularly RNA by PCR. Of the sera stored by the HIV clinic 203 patients are known to be co-infected with HCV who are currently still alive. Once ethics committee approval is obtained we propose to contact these groups of people and see if they would participate in this study. Once consent is obtained we plan to perform the following.
A. Stored sera will be retrospectively examined for the point prevalence of infection with HCV, GBV-C and HIV. These individuals will then be followed up in a prospective manner assessing the progression of liver disease and other factors as outlined in Tables 1 to 4.
B. New subjects attending the Alfred Hospital Hepatitis or HIV clinics will be recruited and followed prospectively also as outlined in Tables 1 to 4.
C. An age and sex matched control group infected with HCV alone will be identified via the Alfred Hospital Hepatitis clinic. This clinic has a large cohort of well-characterized HCV infected subjects that extends back to 1989.
The inclusion and exclusion criteria for the study are as follows:
Inclusion criteria
Exclusion criteria
Where possible information will also be obtained about these people by interview, examining the medical records or discussion with their General Practitioners. Subjects will also be encouraged to attend the hospital in person where a clinical exam can be performed. If insufficient sera is stored further blood will be drawn at this time and examined for HCV, HIV and GBV-C related parameters as outlined in the tables below. A study specific questionnaire will be generated in which subjects will be asked to complete a confidential questionnaire that contains information related to demographic and behavioral factors that may contribute to the acquisition of GBV-C, HCV or HIV infection or various combinations of the above. Demographic variables will include age, sex, country of birth, and occupation. Information relevant to HIV infection including the use of HAART and the presence or absence of AIDS defining syndromes will be obtained. The questionnaire will attempt to identify the approximate time of acquisition of both HCV and HIV. In addition, the extent of liver disease will be assessed, alcohol consumption will be quantified and information will be gathered on previous treatment with Interferon and Ribavirin.
The main outcomes of this study will be liver related morbidity, such as chronic hepatitis, cirrhosis or hepatocellular cancer and overall patient survival. The detailed information contained in the following tables will be obtained from interview, medical records and clinical examination:
Table 1: GBV-C
Table 2: HIV
Table 3: Liver disease (HCV)
Table 4: Survival Data
Results will be statistically examined by univariate and multivariate analysis in terms of clinical outcomes with respect to chronic hepatitis C liver disease between GBV-C positive and negative groups in the HIV co-infected cohort compared with the HCV infected cohort alone. See following Table 5.
Table 5: Study Design
Study Group No.1 HCV +ve, HIV +ve, GBV-C RNA+ve. Study Group No.2 HCV +ve, HIV +ve, GBV-C RNA-ve. Control Group HCV +ve alone.
References relevant to this project (from literature search)
In press.
Ages Eligible for Study: | 18 Years to 80 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Mark D Berzsenyi, MBBS | 0417 574 015 | m.berzsenyi@alfred.org.au |
Australia, Victoria | |
Alfred Hospital | Recruiting |
Melbourne, Victoria, Australia, 3181 | |
Contact: Mark D Berzsenyi, MBBS 0417 574 015 m.berzsenyi@alfred.org.au |
Principal Investigator: | Mark D Berzsenyi, MBBS | Alfred Hospital/Bayside Health |
Study Director: | Stuart R Roberts, MBBS | Alfred Hospital/Bayside Health |
Study ID Numbers: | 35/04 |
Study First Received: | September 13, 2005 |
Last Updated: | June 6, 2007 |
ClinicalTrials.gov Identifier: | NCT00164060 History of Changes |
Health Authority: | Australia: Human Research Ethics Committee |
HCV HIV co-infection |
Virus Diseases Hepatitis Liver Diseases Sexually Transmitted Diseases, Viral Digestive System Diseases HIV Infections |
Sexually Transmitted Diseases Acquired Immunodeficiency Syndrome Hepatitis, Viral, Human Hepatitis C Retroviridae Infections Immunologic Deficiency Syndromes |
Communicable Diseases Liver Diseases RNA Virus Infections Sexually Transmitted Diseases, Viral Slow Virus Diseases Flaviviridae Infections Immune System Diseases Acquired Immunodeficiency Syndrome Hepatitis, Viral, Human Infection |
Immunologic Deficiency Syndromes Hepatitis Virus Diseases Digestive System Diseases HIV Infections Sexually Transmitted Diseases Lentivirus Infections Hepatitis C Retroviridae Infections |