Background: Directly observed therapy (DOT) for antiretroviral therapy (ART) may improve adherence, but there are limited data on its clinical effectiveness.
Methods: Adult patients initiating ART in a public clinic in Cape Town, South Africa, were randomized to treatment-supporter DOT-ART or self-administered ART. DOT-ART patients and supporters received baseline and follow-up training and monitoring. The primary endpoints were the proportions of patients with HIV viral load less than 400 copies/ml and change in CD4 cell counts at 12 and 24 months.
Results: Two hundred and seventy-four patients enrolled (137 in each arm) and baseline characteristics were similar for both arms. The study was stopped early for futility by an independent Data and Safety Monitoring Board. In an intention-to-treat analysis, the proportions of patients with viral load less than 400 copies/ml at 12 months were 72.8% in the DOT-ART arm and 68.4% in the Self-ART arm (P = 0.42). DOT-ART patients had greater median CD4 cell count (cells/μl) increases at 6 months [148 (IQR 84–222) vs. 111 (IQR 44–196) P = 0.02] but similar results at all other time-points. Survival was significantly better in the DOT-ART arm (9 deaths, 6.6%) than in the Self-ART arm (20 deaths, 14.6%; log-rank P = 0.02). In Cox regression analysis, mortality was independently associated with study arm [DOT vs. self-ART; HR 0.38, 95% confidence interval (CI) 0.17–0.86].
Conclusion: DOT-ART showed no effect on virologic outcomes but was associated with greater CD4 cell count increases at 6-month follow-up. Survival was significantly better for DOT-ART compared to Self-ART, but this was not explained by improved virologic or immunologic outcomes.
aDepartments of International Health, USA
bEpidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
cSchool of Public Health and Family Medicine, South Africa
dDepartment of Medicine, Division of Clinical Pharmacology, University of Cape Town, South Africa
eUniversity of Cape Town's Lung Institute, Cape Town, South Africa
fDepartment of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA
gCenter for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
*Present address, Merck Research Laboratories, North Wales, Pennsylvania, USA.
Received 5 November, 2009
Revised 3 March, 2010
Accepted 4 March, 2010
Correspondence to Richard E. Chaisson, MD, Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans St., 1M.08, Baltimore, MD 21231, USA. Tel: +1 410 955 1755; fax: +1 410 955 0740; e-mail: email@example.com