Objective: To compare a quadruple-nucleoside with an efavirenz-containing regimen for treatment of HIV-1 infection.
Design: A randomized, open-label study of the AIDS Clinical Trials Group (ACTG).
Methods: Subjects receiving zidovudine/lamivudine/abacavir on ACTG 5095 with HIV-1 RNA less than 200 copies/ml were randomly assigned to intensify either with tenofovir or efavirenz. Subjects were followed for time to treatment failure, defined as either virological failure or treatment discontinuation. Analyses were intent-to-treat.
Results: One hundred and seventy subjects (21% women; 56% non-white) entered the study. At baseline, 95 and 73% had HIV-1-RNA levels less than 200 and 50 copies/ml, respectively; the median CD4 cell count was 453 cells/μl. Over a median 79 weeks follow-up, 165 (97%) completed the study, three (2%) discontinued, and two (1%) died. Treatment failure occurred in 31 subjects: 18 (21%) (quadruple nucleosides) and 13 (15%) (efavirenz-containing regimen); however the failure–time curves crossed and demonstrated a non-constant treatment effect over time, characterized by more early treatment failures on the efavirenz-containing regimen and more late treatment failures on the four-nucleoside regimen. HIV-1 RNA remained suppressed in more than 88% of subjects to less than 200 copies/ml and in more than 78% to less than 50 copies/ml at weeks 24, 48, and 72, without differences by treatment arm. There were no significant differences between the regimens in CD4 cell increases, time to new grade 3/4 adverse events, or adherence.
Conclusion: The safety, tolerability, and efficacy of the four-nucleoside regimen were not significantly different from the efavirenz-containing regimen. These pilot data support further investigation of the quadruple-nucleoside regimen.
From the aWeill Medical College of Cornell University, New York, New York, USA
bStatistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts, USA
cUniversity of Hawaii, Honolulu, Hawaii, USA
dUniversity of Washington, Seattle, Washington, USA
eUniversity of Southern California Medical Center, Los Angeles, California, USA
fJefferson Medical College, Philadelphia, Pennsylvania, USA
gOhio State University, Columbus, Ohio, USA
hUniversity of California, San Francisco, USA
iUniversity of Rochester, Rochester, New York, USA
jDivision of AIDS, National Institute of Allergy and Infectious Disease, Bethesda, Maryland, USA
kBrigham and Womens' Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Received 8 September, 2006
Revised 7 November, 2006
Accepted 14 November, 2006
Correspondence to Roy M. Gulick, MD, MPH, Weill Medical College of Cornell University, Box 566, 525 East 68th Street, New York, NY 10021, USA. Tel: +1 212 746 4177; fax: ++1 212 746 8852; e-mail: email@example.com