UNIVERSITY OF NORTH CAROLINA AIDS CLINICAL STUDY GROUP

We propose a multidisciplinary research program which will
integrate substantial institutional expertise in infectious diseases,
retrovirology and herpes viruses, antiviral agents, epidemiology,
biostatistics, and numerous clinical resources, focusing on the
evaluation of novel antiretroviral therapies in HIV-infected
persons. In Project 1 a group of clinical investigators with diverse
backgrounds will collectively study new antiviral compounds or
novel antiviral combinations. Studies will determine the safety
and tolerance of such therapies in small groups of patients who
will be intensively studied for in vivo evidence of antiviral effects
on HIV and other virus infections (EBV, CMV, hepatitis B) that
may be cofactors in AIDS pathogenesis. Patients will include
hemophiliacs from a large, well studied cohort, and HIV-infected
individuals from other risk groups. The pharmacokinetics of
antiviral compounds will be closely monitored, as will the impact
of liver disease, common in hemophiliacs, on metabolism of
antiviral compounds such as AZT. Projects 2-5 comprise a BASIC
RESEARCH COMPONENT and explore aspects of HIV biology
relevant to antiviral therapy. In Project 2, antiviral synergy and
resistance and the mechanisms underlying these phenomena will
be studied in different HIV isolates. Project 3 will examine
biologic interactions between EBV, CMV and HIV in vitro, and
Project 4 will study the role of CMV in progression of
immunodeficiency among HIV-infected hemophiliacs. These
related projects will provide important information concerning
the role of putative cofactor viruses in AIDS pathogenesis, and
their potential importance as targets for antiviral therapy.
Project 5 will study the molecular evolution of HIV isolates
recovered from sexual partners. This study will provide
information concerning the sexual transmission of HIV and forces
acting on evolution of the env gene. Project 6 (OUTREACH
COMPONENT) will evaluate contact tracing among HIV-infected
persons identified in a low prevalence state, important because
effective contact tracing will be essential for broad application of
antiviral therapy. All of the above projects will be supported by a
Clinical Retrovirology Laboratory core with sophisticated
virologic and serologic capabilities.