We propose to coordinate our study of the epidemiology, etiology and treatment of epidemic acquired immune deficiency syndrome (AIDS) through the Kaposi's Sarcoma (KS) Clinic at UCSF. Support for this clinic and for an associated specimen bank is central to our proposal. We will study the following four aspects of AIDS. 1. Epidemiology- We will utilize the large but compact homosexual community in San Francisco to determine the risk factors and communicability of AIDS. A case-controlled study will extend the earlier investigation by the CDC, focussing on preceding infections, sexual habits and drug use. Communicability will be addressed by interviews and examinations of sexual contacts of AIDS patients. Also, a cohort of healthy homosexual men will be followed for the development of immune impairment. 2. Immunology- AIDS immune pathogenesis will be approached by lymphoid cell subset quantitation and functional analyses. We will study AIDS serum for a soluble immunosuppressive factor such as an auto-anti-idiotypic antibody or virus-specific immune complex. The role of interleukins (IL) in AIDS will be investigated by determining the production of and sensitivity to IL 1 and 2 in various lymphoid cells. 3. Virology- We will explore two hypotheses of a viral etiology of AIDS: one, that a novel virus causes prolonged immune deficiency; two, that the deficit results from multiple, high dose exposures to a known virus such as cytomegalovirus (CMV). To investigate the first, specimens from AIDS patients will be studied in vitro and also innoculated into mice and guinea pigs. The health and immune competence of all animals will be studied serially. To assess the role of CMV in AIDS we will identify a group of homosexual men who are CMV seronegative. Subjects will be evaluated regularly for sero-conversion (evidence of recent CMV infection) and immune competency. 4. Therapy- Successful therapy of the lymphadenopathy syndrom (LNS) and KS must allow recovery of immune competence. The risk of malignant transformation in LNS will be established prospectively. If warranted, immune modulating therapy is proposed. For KS, national Phase II chemotherapy trials are described, beginning with ICRF-159, an agent which inhibits antiogenesis. Institutional biologic response modifier trials, such as ours with interferon, are discussed.
Showing the most recent 10 out of 37 publications
