We propose to conduct a prospective study of the natural history of human immunodeficiency virus (HIV) infections among 1,000 active intravenous drug users (IVDCUs) in the Greater Baltimore area who are seronegative at baseline. The overall objective is to identify and quantify the ceteminants of risk or HIV infection associated with spe- cific drug-use related and sexual behaviors and to study the early natural history of HIV infection. A sample of 1500 seronegative ' active IVDUs who have been recruited an screened for HIV infection in another NIDA-funged-study of the natural history of HIV infection in seropositive IVDUs (DA04334, the ALIVE study) will be accessed. Those identified as active IVDUs i@thin the last year will be enrolled in follow-up studies and re-screened at six month intervals for three years for seroconversion. At the follow-up visits, individuals will have repeat serologic screening for HIV infection, an interview for IV drug use and sexual practices, and a medical history with directe physical examination. In addition interview data will be obtained on their knowledge and attitudes about risk behavior and impediments to risk reduction. The prevalence of use of various methods of cleaning and disinfecting drug paraphernalia and the effectiveness of these methods in interupting HIV transmission will be estimated. We estimate, conservatively, that 2-5% of study subjects will seroconvert to HIV virus annually, yielding 20-50 subjects during each year of the study. The study design will allow for nested case-control studies within a cohort study. We will compare th IVDUs who remain seronegative with seroconvertors, and seropositive IVDUs and-homosexual men who are seropositive, seronegative or have seroconverted, using data from the Baltimore MACS cohort of homosexual men being studied at Johns Hopkins. The rate of progression of HIV infection among IVDUs with incident infections will provide cri tical epidemiologic data to compare the rates of progression in IVDUs and homosexual men and to define the factors related to disease progression in this important risk group. In addition, non-drug using sexual partners of IVDUs in this cohort who seroconvert and the ALIVE cohort of seropositives will be interviewed and screened for HIN antibodies to determine rates of sexual transmission, risks of specific sexual practices, and markers for infectivity. ince sexual partners of seropositive IVDUs are the major risk group for heterosexual and neonatal transmission in the U.S., careful studies of this population are urgently needed.
