OBJECTIVES: We studied the evolution of the patient-provider relationship (PPR) in HIV-infected patients who reported trustful relationships at highly active antiretroviral therapy (HAART) treatment initiation. METHODS: Psychosocial and clinical data were obtained from the French ANRS CO-8 cohort. Break of trust was defined using the question "How much do you trust the provider who usually treats you at this clinic?" Predictors of a possible break of trust during the 5 years after initiating treatment for those patients reporting a trustful PPR at month 0 were identified using a Cox model. RESULTS: During a total follow-up of 3,044 person-years, 68 (7%) patients reported having at least 1 break of trust in their PPR. Break of trust is independently associated with younger age, dissatisfaction with medical staff's explanations, cigarette smoking, and self-reported side effects and is independently inversely associated with severe HIV-related events and changes of treatment. CONCLUSIONS: A patient's break of trust in his provider is relatively infrequent. Accounting for the influence of immunologic status and psychosocial factors, self-reported side effects are shown to be detrimental to the PPR. Interestingly, clinical events and changes of treatment prevent a possible break of trust by reinforcing the provider's role. These results underline the importance of recognizing a patient's perceived secondary effects and developing appropriate care.