Host Genetic Factors Influencing HIV1 and HCV Viral Loads and AIDS Clinical Progression in a Hemophilia Cohort (HGDS-3)

Background:

Over 80% of the hemophiliac population who became infected with HIV prior to 1985 are also
co-infected with HCV. Thus, hemophiliacs represent an important population for studies of the
natural history of these chronic viral infections.

Moreover, the high rate of co-infection makes it an ideal group for assessing the interaction
between the viruses and the relationship between viral specific immune responses and clinical
progression.

Although the hemophiliac poulation is unique, co-infection by these chronic viral pathogens
is becoming increasingly common, particularly amongst intravenous drug users, who account for
approximately 25% of the HIV-1 epidemic in the United States.

Objectives:

The aim of this study is to determine if polymorphism in the promoter region of TH1 and Th2
cytokines are associated with (1) intracellular cytokines levels in CD4 + Tcells, (2) Human
Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) viral loads, and (3) clinical
progression of HIV1 to AIDS in hemophiliacs.

Eligibility:

The current proposal will investigate host genetic factors related to HIV-1 and HCV
immunopathogenesis by studying children and adolescents enrolled in the Hemophilia Growth and
Development Study (HGDS).

Design:

This study is in collaboration with the principle investigators of the Hemophilia Growth and
Development Study (HGDS) as part of a grant "Pathogenesis of HIV and HCV in Hemophilia:
HGDS-3" with funding support by NIH/NICHD for the period 9/25/01 through 8/31/2005.

This multicenter, United States study represents a well-characterized, prospectively followed
cohort of HCV-infected hemophiliacs, of whom 207 are HIV-1 co-infected.

Enrollment of the hemophiliac cohort was completed between 3/89 and 6/90. The final
observation of the cohort (follow-up 16) was concluded during 7/98. No new samples or
clinical data will be collected on this population.

The LGD plays two roles in this project: (1) an administrative role overseeing the
withdrawal, handling, and transport of samples from the HGDS/LGD and central repositories at
the NCI-Frederick, and (2) a scientific role continuing investigations to determine the role
of host genetic factors in Th1 and Th2 immune response and regulation of HCV and HIV viral
replication..