This study aimed to characterize the experience of having a treatment supporter among HIV-infected South African patients enrolled in a randomized controlled trial that compared the efficacy of patient-nominated treatment supporters administering partial directly observed antiretroviral therapy (DOT-ART) versus selfadministered ART (Self-ART). Results of the parent study showed no virologic or sustained immunologic differences between groups, but revealed a significant survival benefit among the DOT-ART group. One hypothesis is that this survival benefit may be explained by differences in the training and involvement of the treatment supporters between groups. In the current study, results from a semi-structured exit interview of 172 participants indicate that most participants in both arms maintained a positive, satisfying relationship with a single supporter, typically family member or friend. Most patients (82.6%) perceived supporters as helpful with medication adherence, with no significant difference between groups ( p = 0.752). Additionally, supporters provided emotional, instrumental, and material support. DOT-ART patients were more likely than Self-ART patients to report that their supporter helped to decrease drug or alcohol use (p = 0.03). Patients identified supporter trustworthiness, availability, good communication and reciprocity of support as factors beneficial to a successful relationship. These results suggest: (1) Patient-nominated peers are feasible candidates for ART supporters in this resource-constrained setting; (2) In addition to assistance with medications, treatment supporters have the capacity to promote healthy behaviors and provide other types of support, which may contribute to improved outcomes, particularly with enhanced training; (3) Trustworthiness, availability, good communication, and reciprocity are key factors in a successful patient-supporter relationship.