Transmission of HIV-1 within the heterosexual community in the U.S. largely occurs through contact with high-risk groups, commonly with IDUs. However, little is known about whether opiate use influences the sexual transmission of HIV-1. This application for an NRSA post-doctoral fellowship proposes studies designed to address the risk for sexual transmission of HIV-1 to and by IDUs. This award will support career development for Dr. Kristen V. Khanna under the direction of Dr. Richard Markham, an Associate Professor at the JHSPH. The JHSPH provides an outstanding environment for research training and supports an atmosphere of collaboration, with sensitivity to the unique issues involved in studying drugs of abuse. Dr. Khanna's career development plan includes interaction with world-renown investigators in HIV and drug addiction, daily opportunities for seminars and workshops, development as a mentor, and the publication of work resulting from these studies. The research plan, which examines the effect of opiate exposure in vitro, in vivo in IDU, and in opiate receptor knock-out mice, fully encompasses what is necessary for Dr. Khanna to be successful in her immediate and long-term research goals. Dr. Khanna has access to two IDU cohorts (the AIDS Linked to the Intra-Venous Experience (ALIVE) Study, and the HIV Epidemiology Research Study (HERS), on the natural history of HIV in women). The studies outlined in this proposal make use of these already established cohorts and will provide new information on the effect of opiate use on the sexual transmission of HIV-1.