An ambitious new program funded by the National Institute of Allergy and Infectious Diseases (NIAID) focuses on innovative ways to study how HIV-1 causes disease in adults.
Scientists at six research units will use interventions, such as highly active antiretroviral therapy given in the acute and early phases of infection, to increase their understanding of the mechanisms and course of HIV disease. They will also directly study the outcomes of these interventions.
The research units supported by this new effort, called the Acute Infection and Early Disease Research Program, will have both basic and clinical components, and will receive four-year awards totaling $6.7 million for the first year. The units are located at the Fred Hutchinson Cancer Center in Seattle, the Aaron Diamond AIDS Research Center in New York, the University of California at San Francisco, the Johns Hopkins University School of Medicine in Baltimore, the University of Colorado Health Sciences Center in Denver, and the University of Alabama at Birmingham.
This program will build upon recent advances in understanding AIDS pathogenesis, developing potent antiretroviral therapies and creating effective tools for measuring HIV in the blood. "The important bridge that this program will provide between basic and clinical research may have profound implications for treatment and prevention of HIV disease," says Anthony S. Fauci, M.D., director of NIAID.
Scientists believe that events occurring during acute and early infection may determine the ultimate course of disease in an individual. In the first weeks of infection, individuals develop very high levels of HIV circulating in the blood (viral load)reflecting active viral replication. Earlier studies have shown that people with more HIV in their blood during the first six months of infection are at greater risk of developing AIDS more rapidly than those with less virus. This suggests that the degree of suppression of viral replication by the immune system during acute infection may be a critical factor in later disease. It also suggests that intervention with active drugs during this phase of disease might improve outcome many years later. There are early changes to the immune system; most people with acute infection have a persistent decline in immune function. Scientists in the new program plan to study the roles of both host and viral factors in this decline. Identification of such factors could improve prevention and treatment strategies.
Approximately 40,000 people are newly infected with HIV each year in the United States. Nonetheless, acute HIV infection is under-diagnosed because the symptoms associated with early HIV infection (fever, rash and fatigue) are common to many other conditions. "Because of the difficulties in identifying individuals during the acute and early stages of infection, few studies have examined the impact of early antiretroviral therapy on viral and immunologic factors," says Jack Killen, M.D., director of the Division of AIDS at NIAID. "The studies proposed by this group of renowned scientists are tremendously exciting."
Following are the six Acute Infection and Early Disease Research Program principal investigators and their proposed research plans.
Lawrence Corey, M.D., of the Fred Hutchinson Cancer Center in Seattle, will define the role of cytotoxic T lymphocytes (CTLs)in controlling early infection and determine whether initial HIV-1 specific CD8+ T cell responses are predictive of subsequent disease progression.
David Ho, M.D., of the Aaron Diamond AIDS Research Center in New York, will examine the effect of antiretroviral therapy on virus in the blood and lymphoid tissue and on CTL response. His team also proposes to monitor B and T cell responses.
Jay Levy, M.D., of the University of California at San Francisco, will evaluate the effect of therapy on viral load, the rate at which the virus is produced, immune activation and CD8+ T cell function.
Joe Margolick, M.D., of the Johns Hopkins University School of Medicine, will explore how the virus adapts to the host during early infection and determine whether treatment during acute infection allows the immune system to recover its function.
Robert Schooley, M.D., of the University of Colorado Health Sciences Center in Denver, proposes to examine the differences among virus in the lymph tissue and blood, and to determine the types of cells that are involved in active versus latent infection.
George Shaw, M.D., Ph.D., of the University of Alabama at Birmingham, will study where HIV is distributed and sequestered in the body and its form in various reservoirs, the dynamics of virus reproduction and the host immunogenetic profile.
NIAID, a component of the National Institutes of Health (NIH), supports research on AIDS, tuberculosis and other infectious diseases, as well as allergies and immunology. NIH is an agency of the U.S. Department of Health and Human Services.
NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov