Stress, substance use and medication beliefs are among the most frequently cited barriers to HIV treatment adherence. This study used longitudinal techniques to examine the temporal relationship between these barriers and adherence among clients attending treatment adherence support programs in New York State. A total of 4,155 interview pairs were analyzed across three interview transitions. Multinomial models were constructed with four-category change-based independent variables (e.g., low stress at both interviews, low stress at interview 1 and high stress at interview 2, high stress at interview 1 and low stress at interview 2, high stress at both interviews) that predicted a similarly constructed four-category adherence change variable. Clients who reported positive changes in stress, substance use, or medication beliefs were more likely to change from being nonadherent to being adherent, while clients who reported negative changes were more likely to change from being adherent to being nonadherent. To improve or maintain adherence over time, strategies should be used that facilitate positive changes-and prevent negative changes-in stress, substance use, and medication beliefs.