Background:  HIV⁺ drug users have derived less benefit from ART than others. While directly administered ART (DAART) has demonstrated impressive biological benefits compared with self-administered therapy among HIV⁺ drug users, the persistence of DAART following transition to self-administered therapy has not been examined.

Methods:  We conducted a community-based, prospective, randomized controlled trial of 6 months of DAART compared with self-administered therapy in New Haven, Connecticut. The primary outcome was the proportion of subjects who achieved virological success at 6 months post-intervention, defined as achieving either a ≥1.0 log₁₀ reduction from baseline or HIV-1 RNA <400 copies/mL. Secondary outcomes included the change from baseline in HIV-1 RNA and CD4 lymphocyte count.

Results:  At the end of 6 months, the DAART group (n = 88) was more likely to have a virological success (70.5% vs 54.7%, p = 0.02), mean reduction in HIV-1 RNA level (1.16 log₁₀ vs 0.29 log₁₀ copies/mL; p = 0.03) and a change in CD4 lympocyte count (+58.8 vs –24.0 cells/mL; p = 0.002). After an additional 6 months of observation when all subjects received medications as self-administered therapy, the DAART (n = 82) and self-administered therapy (n = 52) arms did not differ on virological success (DAART 58.0% vs self-administered therapy 56.6%, p = 0.64), mean reduction in log₁₀ HIV-1 RNA (–0.79 vs –0.31 log₁₀ copies/mL, p = 0.53), nor mean change in CD4 lymphocyte count (+60.2 vs –15.4 cells/mL, p = 0.12). In the multivariate analysis, only high levels of social support significantly predicted virological success.

Conclusions:  This analysis, from the first randomized controlled trial of DAART among active drug users, is the first to examine the post-intervention effects of DAART. Failure to show the persistence of DAART at improving virological outcomes suggests that further studies in HIV⁺ drug users should examine a longer DAART duration or incorporation of self-efficacy or social support components, which may provide durability to this otherwise effective intervention.