DESCRIPTION (provided by applicant): This application in response to NIDA PAR 12-222 Cohort Studies of HIV/AIDS and Substance Use (U01) seeks to leverage extensive existing infrastructure and cohorts at the University of California, Los Angeles to launch a new cohort of substance using minority (Black or Hispanic) men who have sex with men (MMSM). The epidemic of HIV among MMSM in the US and locally in Los Angeles County (LAC) may be driven by effects of substance use on adherence to treatment regimens and bio-behavioral prevention and enhanced by high prevalence networks. Proposed investigators lead the science on studying associations between non-injection drug use, risk behaviors and infectious disease among MSM, and contribute a broad portfolio of inter-disciplinary work from immunology and basic science to epidemiology, prevention and treatment. The work proposed leverages existing cohorts including the Multicenter AIDS Cohort (MACS) and existing repositories and builds on preliminary work to guide assembly of a cohort for the study of basic and behavioral factors in younger MMSM who actively use substances and engage transmission risks. Establishing a cohort of young active substance users, particularly stimulant users, who have poor histories of antiretroviral treatment (ART) adherence as marked by measurable and clinically relevant Plasma Viral Load (PVL) will enable important tests of biological influences of substances on immune function in MMSM. This cohort is central to prevention and treatment efforts and will provide well-characterized, extensive repository samples for leveraged use with other cohorts, networks' and individual's studies. The MMSM will be: (i) HIV-positive with viral load >5000 copies/ml or (ii) HIV-negative at high risk for HIV infection (unprotected anal intercourse in the past 6 months). This unique cohort will facilitate studies on interactions between substance use and HIV progression and/or transmission, which are of critical public health significance. This cohort of MMSM will characterize: (i) effects substance use on behavioral and network level risk in exposed and infected MMSM on acquisition of HIV and other sexually transmitted infections (STIs: gonorrhea, Chlamydia, syphilis, Hepatitis C (HCV)); and (ii) the extent to which substance use in MMSM facilitates behaviors that transmit HIV compared to non-drug using MMSM. The application also proposes to develop and maintain a bio repository that is HIPAA-compliant, technologically-current and DAIDS Network interfaced that includes a scientific advisory committee. This cohort will comprise 620 MMSM with repeated data visits (from 1,080 MMSM). At least half of these MMSM will be active substance users and younger than age 30.

PUBLIC HEALTH RELEVANCE: The public health significance of the work described is very high in that the project seeks to establish a cohort of minority men who have sex with men who are active substance users who are either HIV-positive and have measurable viral load (indicating intermittent antiretroviral medication adherence) or who are HIV-negative and engage high risk sexual transmission behaviors for sexually transmitted infections, including HIV, gonorrhea, Chlamydia, syphilis and Hepatitis C. It is the composition of this cohort that confers outstanding impact. Establishing the cohort and the corresponding UCLA Bio repository for storing samples from these cohort members will provide a matchless platform to investigate basic, biological and behavioral effects of active substance use, especially stimulant use (i.e., cocaine, crack, methamphetamine, amphetamine and Ecstasy) in minority MSM who are sexually active (i.e., younger than existing cohort members) and who are inconsistent with antiretroviral medications. Findings from the proposed set of specific aims and from future research that will be made possible by establishment of the cohort and the UCLA Biorepository will enable important tests of biological influences of substances, especially stimulants, on immune function and HIV infection in very high risk MMSM, both HIV positive and HIV negative. This novel cohort will optimize our chances to clarify fundamental questions that have challenged NIDA/NIAID in curtailing infections in these populations.