We contrast a typical “social determinants of health” framing with a more dynamic and complex “social determination of health” framing to analyze HIV-related sexual risk among women in low-income, segregated neighborhoods in New Haven, CT. Using an abductive approach, we analyze repeated, longitudinal qualitative interviews conducted over a 2-year period with a sample of 14 HIV-negative women who engaged in sex with men during the study period. Three case studies are presented to demonstrate how behaviors and sexual practices typically described as HIV “risks” can be understood as part of the work of establishing and maintaining monogamous committed relationships, which we call “relationship work,” shaped in a context characterized by housing vulnerabilities and the many manifestations of mass incarceration and the surveillance state. We conclude by suggesting that for these women, their relationship work is the work of HIV prevention and life in low-income segregated neighborhoods is their HIV-related risk.