Studying Genes in Women With Hepatitis C Virus, Hepatitis B Virus, Human Papillomavirus, and/or HIV Infection

• Infection [ Designated as safety issue: No ]
  

OBJECTIVES:

• Examine the role of HLA and killer immunoglobulin-like receptors (KIR) in the natural history of human papillomavirus (HPV), hepatitis C virus (HCV), and hepatitis B virus (HBV) in HIV-positive and HIV-negative women.
• Test the hypothesis that KIR and HLA genotype may play a role in the pathogenesis of HIV, HPV, HCV, and HBV infection.
• Determine the relationship between KIR and HLA genes and risk of HIV infection, according to likely source of virus exposure (sexual versus IV) and demographic factors such as race.
• Determine the relationship between KIR and HLA genes and CD4+ cell counts and serum HIV RNA levels.
• Determine the relationship between KIR and HLA genes and incidence of AIDS and other clinical endpoints, including AIDS-associated malignancies and opportunistic infections.
• Determine the relationship between KIR and HLA genes and the response to highly active antiretroviral treatment (HAART), as measured by increases in CD4+ T-cell levels, reduction in serum HIV RNA levels, and reduction in AIDS rates.
• Determine the relationship between KIR and HLA genes and risk of HCV infection among injecting drug users, according to viral subtype and demographic factors, such as race.
• Determine the relationship between KIR and HLA genes and persistence of HCV infection.
• Determine the relationship between KIR and HLA genes and incidence of HCV-related end-stage liver disease and/or hepatocellular carcinoma.
• Determine the relationship between KIR and HLA genes and response to immunotherapy, as measured by viral load and liver function tests.
• Determine the relationship between KIR and HLA genes and the natural history of HPV and cervical dysplasia in HIV-positive and HIV-negative women.
• Determine the relationship between KIR and HLA genes and persistence of HBV infection.
• Determine the relationship between KIR and HLA genes and incidence of HBV-related end-stage liver disease and/or hepatocellular carcinoma.

OUTLINE: This is a multicenter study.

Blood samples are analyzed for genomic DNA isolated from lymphoblastoid B-cell lines or from peripheral blood lymphocytes and used for genotyping of HLA and killer immunoglobulin-like receptors (KIR) genes. High-resolution HLA class I and class II genotyping is performed using the HLA class I genes (HLA-A, -B, -C), which are amplified using polymerase chain reaction (PCR) and sequenced.

Previously collected clinical data is also evaluated. Patients were followed every 6 months on the Women's Interagency HIV Study and underwent physical and gynecological examinations and completed questionnaires. Blood samples, cervical lavage specimens, and cervical cytology samples were also collected at that time.