PROJECT SUMMARY/ABSTRACT: SEX & GENDER SCIENTIFIC WORKING GROUP 1 There are notable sex- and gender-specific differences in the manifestations of both treated and untreated HIV-1 infection, but it remains to be unequivocally determined whether these are due to intrinsic differences in immunological responses, differential susceptibility to the virus, behavioral modulators, effects due to hormonal differences, or a combination of all these factors. Moreover, although more than 50% of people with HIV are either cis- or transgender women, their under-enrollment in clinical studies has greatly limited our understanding of sex and gender differences in HIV acquisition, mechanisms of immunity and latency, responses to antiretroviral drugs, and behavioral tendencies, such as those driven by the socioeconomic challenges of gender inequity and risk of violence. Addressing these crucial knowledge gaps on sex and gender differences in HIV will facilitate the development of targeted strategies for HIV prevention, treatment, and cure, which are imperative to the goal of globally eradicating HIV infection. The merger of the HIV research communities at CWRU and Pitt in the current application to form the RUSTBELT CFAR has enabled the Sex & Gender SWG1 to assemble an exceptional multidisciplinary team of basic, clinical, translational, and behavioral investigators, each of whom has conducted at least one study on the role of gender or sex in HIV infection or treatment, or have expertise related to the transgender community. Building on the unique strengths of each institution, the Sex & Gender SWG1 will work closely with the RUSTBELT CFAR Cores to achieve the following Specific Aims: (1) To engage CFAR members in research involving sex and gender differences in HIV pathogenesis. (2) To facilitate incorporation of sex and gender differences in treatment, prevention, and cure-related HIV research. (3) To strategically coordinate a formal mentorship program to make junior investigators aware of resources to study Sex & Gender. The success of the Sex & Gender SWG1 will be evaluated based on a well-defined set of key performance metrics. Thus, by taking advantage of the strong HIV prevention, pathogenesis, and cure research that is ongoing within the RUSTBELT CFAR and combining it with our experts in behavioral sciences and public health, the Sex & Gender SWG1 is ideally placed to provide unique insights into the control and management of the national and global HIV epidemics.