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Intensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression

Gulick, Roy Ma; Lalama, Christina Mb; Ribaudo, Heather Jb; Shikuma, Cecilia Mc; Schackman, Bruce Ra; Schouten, Jeffreyd; Squires, Kathleen Ee,f; Koletar, Susan Lg; Pilcher, Christopher Dh; Reichman, Richard Ci; Klingman, Karin Lj; Kuritzkes, Daniel Rk

doi: 10.1097/QAD.0b013e32805e8753
Clinical Science

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: rgulick@med.cornell.edu

© 2007 Lippincott Williams & Wilkins, Inc.