Despite the rising number of new HIV infections among youth, few tailored interventions for youth living with HIV (YLH) have been developed and rigorously tested. Developing tailored interventions necessitates identifying different profiles of YLH and understanding how risk and protective factors cluster together. Obtaining this critical information requires accessing a sufficiently large sample of YLH from diverse geographic settings such as those available through the Adolescent Trials Network for HIV Interventions (ATN). We recruited a cross-sectional sample of 1,712 YLH from ATN clinics; participants completed a survey on psychosocial and health factors. Using latent class analysis on nine composite variables representing risk factors, we identified five classes distinguished by substance use, sexual behavior, and pregnancy history and differing on health outcomes. Findings suggest a need for tailored interventions addressing multiple risky behaviors of HIV-infected youth and research to clarify how intervention effectiveness may differ by risk profile.