Many Cells Invaded During Primary Symptomatic HIV Infection

National Institute of Allergy and Infectious Diseases 'ae EMBARGOED FOR RELEASE NATIONAL INSTITUTES OF HEALTH Monday, July 20, 1992 Marion E. Glick 9:45 a.m. (3:45 a.m. EDT) [phone] Many Cells Invaded During Primary Symptomatic HIV Infection Results obtained from the first study to directly determine the replication of HIV in peripheral blood mononuclear cells during the initial weeks of primary symptomatic infection indicate a high frequency of infected cells actively producing virus, according to investigators from the National Institute of Allergy and Infectious Diseases (NIALD) and the University of Alabama in Birmingham. For the study, investigators followed individuals presented to a hospital after having been potentially exposed to HIV infection. When the participants first developed symptoms of primary infection, similar to the flu with diarrhea and fever, the investigators began to collect blood samples. Later, when the participants tested positive for HIV infection, the investigators examined the stored blood and additional blood samples taken for two months. Cecilia Graziosi, Ph.D., coprincipal investigator of the study with Giuseppe Pantaleo, M.D., plans to present the findings July 20 at the VIII International Conference on AIDS in Amsterdam. The investigators used the laboratory test polymerase chain reaction (PCR) to examine the number of infected cells in the blood as well as the degree of virus replication. "We see a burst of virus production for a very short period of time," says Dr. Graziosi. "Other studies have shown that later, during the period of clinical latency of HIV disease for example, far fewer H1V-infected cells are actively producing virus in the blood." (more) 1111III 59IIIIIIIIIIIIIIIIIIIIIIIIII 5571095.0239.002

r The investigators found that during the first week after the onset of symptoms the manufacture of the virus's structural and regulatory proteins had peaked and then quickly slowed down, almost ceasing during the remainder of the two-month study. The slow-down, or down-regulation, of HIV production, Graziosi explains, may be related to the emergence of an immune response to the virus. "However," she adds, "we are not certain what precise role the immune system plays in the down-regulation of the virus and the clearance of HIV-infected cells. Something else, such as sequestering of HIV-infected cells in lymphoid tissue, may be occurring." "These observations help explain the wide dissemination of virus that occurs during the early stage of HIV infection and may prove helpful in the rational design of therapeutic regimens to interrupt this process," says NIAID director Anthony S. Fauci, M.D., co-author of the study. Drs. Fauci, Graziosi and Pantaleo's coinvestigators include, from the Laboratory of Immunoregulation at NIAID, James F. Demarest, and from Alabama, Michael Saag, M.D., and George Shaw, M.D., Ph.D. Dr. Fauci directs the laboratory. NIAID, one of 13 research institutes of the National Institutes of Health, investigates allergies, immunology and infectious diseases. In addition to scientists working in NIAID laboratories in Bethesda, Md., and Hamilton, Mont., the institute supports scientists at U.S. universities, medical schools and research institutions. The study, "Analysis of Viral Burden and Expression During Primary HIV Infection," will be presented during the session, "Viral Spread within the Host," on July 20. L