Trial Information

A Pilot Study of the Patterns of Cellular Gene Expression in HIV-1 Patients Following Clinical Events Which Increase Plasma Virus Concentrations

The factors that influence HIV disease progression are not well understood. While larger
amounts of circulating virus (high 'viral loads') predict future adverse clinical events,
many of the clinical factors responsible for high viral loads and disease progression remain
unknown. Certain clinical events and defined interventions are associated with increases in
plasma viral RNA concentrations. One of these clinical interventions is immunization;
immunization with several vaccines have been shown to increase plasma HIV RNA
concentrations. Even though vaccination can lead to transient increases in plasma HIV
concentrations, certain vaccines, including influenza vaccine, are still recommended for HIV
patients because the risks of the disease targeted by the immunization are held to be
greater than the immunization itself. Therefore, immunization with influenza vaccine can be
considered a model, clinically indicated intervention, given at a known time which
stimulates HIV replication. For influenza immunization, and for other treatments leading to
increases in viral RNA concentrations, detailed knowledge of the regulatory events that
mediate the increase in RNA concentrations is not available. We hypothesize that
immunization with influenza vaccine, and perhaps other immune stimulatory events, lead to an
increase in HIV replication through a regulatory system involving cytokines, signal
transduction systems, transcription factors, effects on the cell cycle, and increased
expression of additional gene products needed for viral replication, such as genes of the
nucleic acid biosynthetic pathways. While experiments aimed at investigating one or another
particular part of this regulatory system can be performed with traditionally available
technologies, such technologies cannot provide comprehensive information concerning a large
number of the regulatory events that may be involved in mediating the increase in HIV RNA
concentration. In this protocol, we aim to develop the methodologies needed to determine
changes in expression of many of the genes which may be involved in mediating the regulation
of HIV expression in HIV-infected patients using cDNA microarray technologies. Once the
methodologies are developed, such work may provide new insights into the regulatory systems
controlling HIV expression in HIV-infected patients may provide new insights into the
pathogenesis of HIV disease.