BACKGROUND: The reduction of HIV transmission risk behaviors among those infected with HIV remains a major global health priority. Psychosocial characteristics have proven to be important correlates of sexual transmission risk behaviors in high-income countries, but little attention has focused on the influence of psychosocial and psychological factors on sexual transmission risk behaviors in African cohorts. METHODOLOGY AND PRINCIPAL FINDINGS: The CHAT Study enrolled a representative sample of 499 HIV-infected patients in established HIV care and 267 newly diagnosed HIV-infected individuals from the Kilimanjaro Region of Tanzania. Participants completed in-person interviews every 6 months for 3 years. Using logistic random effects models to account for repeated observations, we assessed sociodemographic, physical health, and psychosocial predictors of self-reported unprotected sexual intercourse. Among established patients, the proportion reporting any recent unprotected sex was stable, ranging between 6-13% over 3 years. Among newly diagnosed patients, the proportion reporting any unprotected sex dropped from 43% at baseline to 11-21% at 6-36 months. In multivariable models, higher odds of reported unprotected sex was associated with female gender, younger age, being married, better physical health, and greater post-traumatic stress symptoms. In addition, within-individual changes in post-traumatic stress over time coincided with increases in unprotected sex. CONCLUSIONS AND SIGNIFICANCE: Changes in post-traumatic stress symptomatology were associated with changes in sexual transmission risk behaviors in this sample of HIV-infected adults in Tanzania, suggesting the importance of investing in appropriate mental health screening and intervention services for HIV-infected patients, both to improve mental health and to support secondary prevention efforts.