Background:  Modified directly observed therapy (MDOT) is an intervention being used to enhance adherence to HAART, especially in hard to reach populations. We conducted a randomized controlled trial among active substance users to evaluate the effects of MDOT versus standard of care on plasma viral load and HIV resistance.

Methods:  Once-daily HAART regimens were selected for active substance users based on genotypic analysis and past HAART therapy. Individuals were then randomized to receive MDOT or standard of care. Randomization was stratified based on HAART experience. Repeat genotypic analysis was conducted among participants with confirmed virologic failure at assessment points.

Results:  Of the first 65 HAART-experienced participants enrolled, 32 were in the MDOT arm and 33 in the standard of care. Among the MDOT group, the median baseline plasma viral load was 4.74 log₁₀, with 11 (34%) demonstrating resistance to at least 1 of 18 antiretroviral medications. In the standard of care arm, the median plasma viral load was 4.76 log₁₀, with 10 (30%) showing resistance to at least 1 of 18 antiretrovirals. In both arms, the majority had the M184V and/or the K103N mutation. Data was available for 52 participants (26 in each arm) at the 3 month assessment point; the median plasma viral load was 2.53 log₁₀ in the MDOT arm and 4.15 log₁₀ in standard of care (p <0.05). Virologic failure was seen in 5 (19%) participants on MDOT and 11 (42%) in standard of care. HIV drug resistance was detected in 3 of these MDOT participants. One patient who had wild type virus at baseline developed the K103N and of the 2 participants with baseline resistance, 1 developed the K65R, and 1 showed no change in the genotypic pattern. Of the patients failing on the standard of care arm, 7 patients had HIV drug resistance. Of 3 participants who had wild type virus at baseline developed new drug resistant mutations, 2 developed K103N and 1 developed M184V. Of the 4 participants who had drug resistance at baseline, 1 developed the M41L and D67N mutations and 3 showed no change in their genotypic pattern at 3 months.

Conclusions:  Among HAART-experienced substance users, where at least 30% have baseline resistance to HIV medications, MDOT leads to a greater reduction in viral load when compared with standard of care. At 3 months, fewer individuals were on MDOT with HIV drug resistance than in standard of care. MDOT is an effective short-term intervention for HAART-experienced substance users.