A peer-driven intervention (PDI) was developed to support uptake and adherence to highly active antiretroviral therapy (HAART) among women sex workers who use illicit substances in Vancouver, because uptake and adherence continues to be suboptimal. Trends of adherence were examined among women in this program by (1) exposure to the intervention and (2) risk behaviors including drug use and unstable housing. Between January 2007 and January 2008, 20 HIV-positive women were enrolled into the PDI on a rolling basis. PDI participation included weekly peer support meetings, a health advocate (buddy) system, peer outreach service, and onsite nursing care. Adherence was measured directly with pharmacy records (PR) and indirectly with self-report and viral load (VL) outcomes. Participants attended an average of 50 (21-70) PDI meetings. Overall self-reported adherence was high (92%) and most women (11) reported increased adherence from the first to the last 13 PDI meetings attended (average increase = 18%). The number of viral load tests <or=50 copies/mL increased by 40% from the pre-PDI period (1 year before enrollment), to the PDI period (duration enrolled). PR adherence and improvements in VL outcomes were higher among participants with greater housing instability and frequency of injecting/smoking drugs. Despite a very difficult environment to provide HIV care, there is evidence to suggest that the PDI may have had a positive impact on adherence outcomes. Although this would not predict long-term treatment success, the PDI approach to HIV treatment support is a promising program for women who might otherwise be excluded from treatment altogether.