Modified directly observed antiretroviral therapy compared with self-administered therapy in treatment-naive HIV-1-infected patients: a randomized trial
Robert Gross, Camlin Tierney, Adriana Andrade, Christina Lalama, Susan Rosenkranz, Susan H Eshleman, Timothy Flanigan, Jorge Santana, Nadim Salomon, Ronald Reisler, Ilene Wiggins, Evelyn Hogg, Charles Flexner, Donna Mildvan, AIDS Clinical Trials Group A5073 Study Team, Jorge L Santana Bagur, Olga Mendez, Judith A Aberg, Karen Cavanagh, Kathleen Squires, Bartolo Santos, Andrea Weiss, Robin McKenzie, Carl J Fichtenbaum, Fran Hyc, Martha Greenwald, Mitchell Goldman, Karen Tashima, Pamela Poethke, Cathi Basler, Monica Carten, Cindy Firnhaber, Ian Sanne, Aleshia Thomas, David Perlman, Gwen Costantini, Ann Conrad, Kim Whitely, Susan L Koletar, Mark D Hite, Joseph Eron, David Currin, Richard Pollard, Nancy Fitch, Brenda Jackson, Rebecca Basham, Christine Hurley, Mary Adams, Ann C Collier, Beck A Royer, Kim Epperson, Timothy Lane, David Currin, Sue Richard, Henry H Balfour Jr, Christine Fietzer, Hector Bolivar, Margaret A Fischl, Abby Olusanya, Robert Redfield, Charles Davis, Jack Degnan Jack Degnan, Dee Dee Pacheco, Karen Tashima Tashima, Joan Gormley, Sharon Riddler, Carol Oriss, Lorna Nagamine, Scott Souza, Nayef El-Daher, Carol Greisberger, John Black, Beth Zwickl, Timothy Flanigan, Joan Gormley, Marjorie Dehlinger, Robert Gross, Camlin Tierney, Adriana Andrade, Christina Lalama, Susan Rosenkranz, Susan H Eshleman, Timothy Flanigan, Jorge Santana, Nadim Salomon, Ronald Reisler, Ilene Wiggins, Evelyn Hogg, Charles Flexner, Donna Mildvan, AIDS Clinical Trials Group A5073 Study Team, Jorge L Santana Bagur, Olga Mendez, Judith A Aberg, Karen Cavanagh, Kathleen Squires, Bartolo Santos, Andrea Weiss, Robin McKenzie, Carl J Fichtenbaum, Fran Hyc, Martha Greenwald, Mitchell Goldman, Karen Tashima, Pamela Poethke, Cathi Basler, Monica Carten, Cindy Firnhaber, Ian Sanne, Aleshia Thomas, David Perlman, Gwen Costantini, Ann Conrad, Kim Whitely, Susan L Koletar, Mark D Hite, Joseph Eron, David Currin, Richard Pollard, Nancy Fitch, Brenda Jackson, Rebecca Basham, Christine Hurley, Mary Adams, Ann C Collier, Beck A Royer, Kim Epperson, Timothy Lane, David Currin, Sue Richard, Henry H Balfour Jr, Christine Fietzer, Hector Bolivar, Margaret A Fischl, Abby Olusanya, Robert Redfield, Charles Davis, Jack Degnan Jack Degnan, Dee Dee Pacheco, Karen Tashima Tashima, Joan Gormley, Sharon Riddler, Carol Oriss, Lorna Nagamine, Scott Souza, Nayef El-Daher, Carol Greisberger, John Black, Beth Zwickl, Timothy Flanigan, Joan Gormley, Marjorie Dehlinger
Abstract
Background: Success of antiretroviral therapy depends on high rates of adherence, but few interventions are effective. Our objective was to determine if modified directly observed therapy (mDOT) improves initial antiretroviral success.
Methods: In an open-label, randomized trial comparing mDOT (Monday-Friday for 24 weeks) and self-administered therapy with lopinavir/ritonavir soft gel capsules (800 mg/200 mg), emtricitabine (200 mg), and either extended-release stavudine (100 mg) or tenofovir (300 mg), all taken once daily, 82 participants received mDOT and 161, self-administered therapy. Participant eligibility included a plasma human immunodeficiency virus RNA level higher than 2000 copies/mL and being naïve to antiretroviral therapy. A total of 243 participants were predominantly male (79%) (median age, 38 years), with 84 Latinos (35%), 74 non-Latino blacks (30%), and 79 non-Latino whites (33%). The study was conducted at 23 AIDS Clinical Trials Group (ACTG) sites in the United States and 1 site in South Africa between October 2002 and January 2006. The primary outcome was virologic success at week 24 and secondary outcomes were virologic success, clinical progression, and adherence at week 48.
Results: Over 24 weeks, mDOT had greater virologic success (0.91; 95% confidence interval [CI], 0.81 to 0.95) than self-administered therapy (0.84; 95% CI, 0.77 to 0.89), but the difference (0.07; lower bound 95% CI, -0.01) did not reach the prespecified threshold of 0.075. Over 48 weeks, virologic success was not significantly different between mDOT (0.72; 95% CI, 0.61 to 0.81) and self-administered therapy (0.78; 95% CI, 0.70 to 0.84) (difference, -0.06; 95% CI, -0.18 to 0.07 [P = .19]).
Conclusions: The potential benefit of mDOT was marginal and not sustained after discontinuation. Modified DOT should not be incorporated routinely for care of treatment-naïve human immunodeficiency virus type 1-infected patients.
Trial registration: ClinicalTrials.gov NCT00036452.
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Source: PubMed