Superiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: a prospective, randomized, controlled trial

Abstract

Background: Directly administered antiretroviral therapy (DAART) is one approach to improve treatment adherence among human immunodeficiency virus (HIV)-infected drug users.

Methods: In this randomized, controlled trial (ClinicalTrials.gov identifier, NCT00367172), the biological outcomes of a 6-month community intervention of DAART were compared with those of self-administered therapy among HIV-infected drug users. Patients randomized to receive DAART received supervised therapy 5 days per week from workers in a mobile health care van. The primary outcome, using an intention-to-treat approach, was the proportion of patients achieving either a reduction in HIV-1 RNA level of > or = 1.0 log10 copies/mL or an HIV-1 RNA level < or = 400 copies/mL at 6 months. Secondary outcomes included the mean change from baseline in HIV-1 RNA level and CD4+ T lymphocyte count.

Results: Of the 141 patients who met the entry criteria, 88 were randomized to receive DAART, and 53 were randomized to receive self-administered therapy; 74 (84%) of 88 of the patients randomized to receive DAART accepted the intervention. Of the 74 patients who initiated DAART, 51 (69%) completed the full 6-month intervention. At the end of 6 months, a significantly greater proportion of the DAART group achieved the primary outcome (70.5% vs. 54.7; P=.02). Additionally, compared with patients receiving self-administered therapy, patients receiving DAART demonstrated a significantly greater mean reduction in HIV-1 RNA level (-1.16 log10 copies/mL vs. -0.29 log10 copies/mL; P=.03) and mean increase in CD4+ T lymphocyte count (+58.8 cells/microL vs. -24.0 cells/microL; P=.002).

Conclusions: This randomized, controlled trial was, to our knowledge, the first to demonstrate the effectiveness of DAART at improving 6-month virologic outcomes among drug users. These results suggest that DAART should be more widely available in HIV treatment programs that target drug users who have poor adherence to treatment.

Figure 1

Disposition of study patients. DAART, directly administered antiretroviral therapy; ITT, intention-to-treat; SAT, self-administered therapy.

Figure 2

End-of-treatment virologic and immunologic outcomes. A, Proportion of patients achieving virologic success (i.e., an HIV-1 RNA level ≤400 copies/mL or a reduction in HIV-1 RNA level of ≥1.0 log₁₀ copies/mL). B, Mean change in CD4⁺ T lymphocyte count. Reported P values were adjusted for baseline viral load and CD4⁺ T lymphocyte counts; the P value for CD4⁺ T lymphocyte counts represents that from the log-transformed model, which fit the normality assumption better. DAART, directly administered antiretroviral therapy; SAT, self-administered therapy.

Figure 3

Mean change in viral load during the intervention period. Raw values are shown, adjusted for censoring at the lower limits of detection. P values were adjusted for baseline HIV-1 RNA level and CD4⁺ T lymphocyte count. DAART, directly administered antiretroviral therapy; SAT, self-administered therapy.