528   Impact of Directly Observed Therapy on Long-Term Outcomes in HIV Clinical Trials.

M. Fischl*¹, J. Castro¹, R. Monroig¹, E. Scerpella¹, L. Thompson¹, D. Rechtine², and D. Thomas².
¹Univ. of Miami, FL and²Dept. of Corrections, Orlando, FL.

Background:Our objective was to assess directly observed therapy (DOT) in HIV clinical trials.

Methods:Treatment-naive subjects enrolled in 5 clinical trials conducted simultaneously in the AIDS Clinical Research Unit (ACRU) and Department of Corrections (DOC) were included. Subjects received study meds as DOT in the DOC and as self-administered therapy (SAT) in the ACRU. Regimens included 3 or 4 drugs with 2 NRTIs plus either efavirenz (EFV), a protease inhibitor or both. Analysis used an intent-to-treat approach.

Results:A total of 100 subjects were included, 50 in each of the DOT and SAT groups. DOT subjects were more likely to be men (94% vs 80%), black (84% vs 28%), non-Hispanic (90% vs 28%) and IVDUs (32% vs 4%) and had lower CD4 cell counts (246 vs 329 cells/mm³) and higher HIV RNA levels (5.6 vs 5.3 log₁₀). The proportion of subjects with HIV RNA <400 copies/ml was higher for the DOT group compared with the SAT group (p < 0.01); comparing the DOT vs SAT groups: wk 4 (52% vs 55%), wk 8 (76% vs 76%), wk 16 (94% vs 77%), wk 24 (100% vs 76%), wk 32 (100% vs 79%), wk 48 (100% vs 81%), wk 64 (100% vs 81%), wk 72 (90% vs 75%) and wk 80 (95% vs 75%). The proportion of subjects in the SAT group receiving 4-drug regimens was less than for the SAT group overall at 24 wks (64% vs 76%) and at 48 wks (57% vs 81%) and differed the most from the DOT group (57% vs 100%). In contrast, the proportion of subjects in the SAT group receiving an EFV-containing regimen was higher than for the SAT group overall at 24 wks (82% vs 76%) and at 48 wks (94% vs 81%) and differed the least from the DOT group (94% vs 100%).

Conclusions:Subjects in the DOT group had greater short- and long-term virologic responses compared with those in the SAT group. Self-administered four-drug regimens had a blunted response while an EFV-containing regimen had a better response compared with other regimens, suggesting that simplified regimens are likely to improve adherence and outcome.