The treatment outcomes for large-scale public antiretroviral therapy (ART) programs in developing countries, although promising, are still preliminary. The scaling-up of ART in resource-limited settings is inevitably hampered by human resource shortages. Therefore, community support for ART patients may play an important role in achieving favorable treatment outcomes. This study aimed to extend the current literature by investigating how immunological and virological responses to ART, measured at three points in time (after six, 12, and 24 months of ART), are influenced by patient characteristics (age, sex), health literacy (educational level and knowledge about HIV/AIDS), baseline CD4 cell count, baseline viral load, and three forms of community support (treatment buddy, community health worker [CHW], and HIV/AIDS support group). Cross-lagged regression analysis was used to test these relationships in a sample of 268 patients enrolled in the public-sector ART program of the Free State Province of South Africa (2004-2007). After 24 months of ART, 76.4% of patients were classified as treatment successes (viral load < 400 copies/mL, CD4 > or = 200 cells/microL), compared with 64.1% at 12 months and 46.1% at six months. When we examined the predictors of ART success, baseline health and all three community support initiatives had a positive effect on ART outcomes after six months, whereas patient characteristics had little effect. Six months later, patients with the support of a treatment buddy, CHW, or support group had better ART outcomes, whereas the impact of baseline health had diminished. After two years of treatment, community support again emerged as the most important predictor of treatment success. This study confirms that the ART provided by South African public-sector health services is effective. These results provide evidence from the field that communities can be mobilized to sustain these favorable outcomes under conditions of limited human resources for healthcare.