Associations, Outcomes and Genomics of GB Virus C, Hepatitis C Virus and Human Immunodeficiency Virus Infection
Recruitment status was Recruiting
|First Received Date ICMJE||September 13, 2005|
|Last Updated Date||June 6, 2007|
|Start Date ICMJE||February 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00164060 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Associations, Outcomes and Genomics of GB Virus C, Hepatitis C Virus and Human Immunodeficiency Virus Infection|
|Official Title ICMJE||Associations, Outcomes and Genomics of GB Virus C, Hepatitis C Virus and Human Immunodeficiency Virus Infection|
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.
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).
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:
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)
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Defined Population
Observational Model: Natural History
Time Perspective: Longitudinal
Time Perspective: Retrospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||200|
|Completion Date||May 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 80 Years|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||Australia|
|NCT Number ICMJE||NCT00164060|
|Other Study ID Numbers ICMJE||35/04|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Bayside Health|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Bayside Health|
|Verification Date||September 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP