Modified directly observed antiretroviral therapy compared with self-administered therapy in treatment-naive HIV-1-infected patients: a randomized trial.
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.
Gross
Robert
R
Department of Medicine (Infectious Diseases), Center for Clinical Epidemiology and Biostatistics, and Center for Education and Research in Therapeutics, Univ. of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. grossr@mail.med.upenn.edu
Tierney
Camlin
C
Andrade
Adriana
A
Lalama
Christina
C
Rosenkranz
Susan
S
Eshleman
Susan H
SH
Flanigan
Timothy
T
Santana
Jorge
J
Salomon
Nadim
N
Reisler
Ronald
R
Wiggins
Ilene
I
Hogg
Evelyn
E
Flexner
Charles
C
Mildvan
Donna
D
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D000068679:Emtricitabine; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage; D011744:Pyrimidinones / Q000008:administration & dosage; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D018119:Stavudine / Q000008:administration & dosage; D000068698:Tenofovir; D016896:Treatment Outcome; D055815:Young Adult
D019380:Anti-HIV Agents; D063065:Organophosphonates; D011744:Pyrimidinones; D012367:RNA, Viral; D003841:Deoxycytidine; D061466:Lopinavir; D000068698:Tenofovir; D018119:Stavudine; D000068679:Emtricitabine; D000225:Adenine