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Similar efficacy and tolerability of atazanavir compared with atazanavir/ritonavir, each with abacavir/lamivudine after initial suppression with abacavir/lamivudine plus ritonavir-boosted atazanavir in HIV-infected patients

Squires, Kathleen Ea; Young, Benjaminb; DeJesus, Edwinc; Bellos, Nicholaosd; Murphy, Daniele; Zhao, Henry Hf; Patel, Lisa Gf; Ross, Lisa Lf; Wannamaker, Paul Gf; Shaefer, Mark Sg; for the ARIES study team

doi: 10.1097/QAD.0b013e32833bee1b
Clinical Science

Background: Treatment simplification strategies involving induction with a ritonavir (RTV)-boosted (/r) protease inhibitor regimen followed by simplification (without RTV) are appealing because they may offer sustained virologic suppression while minimizing potential long-term adverse effects associated with RTV.

Methods: This open-label, randomized, noninferiority study enrolled 515 antiretroviral therapy-naive patients to receive abacavir/lamivudine plus atazanavir/RTV (ATV/r) followed by randomization at week 36 (N = 419) to maintain or discontinue RTV for an additional 48 weeks. Eligibility for randomization required confirmed HIV RNA level below 50 copies/ml and no virologic failure. Protocol-defined virologic failure after week 36 was confirmed rebound of HIV RNA level at least 400 copies/ml. The primary endpoint was the proportion of patients with HIV RNA level below 50 copies/ml at week 84 (time to loss of virologic response). This study is registered with ClinicalTrials.gov number NCT00440947.

Results: At week 84, noninferiority of ATV to ATV/r (95% confidence interval around the treatment difference −1.75 to 12.48%) was demonstrated with 181 of 210 (86%) patients in the ATV group and 169 of 209 (81%) in the ATV/r group maintaining HIV RNA level below 50 copies/ml. During the randomized phase (weeks 36–84), 10 versus 14% of patients in the ATV and ATV/r arms, respectively, experienced a drug-related grades 2–4 adverse event with hyperbilirubinemia being the most frequently reported (4 versus 10%). The overall rate of protocol-defined virologic failure was 2%; no patient had virus that developed a major protease inhibitor mutation.

Conclusion: ATV in combination with abacavir/lamivudine is a potent and well tolerated regimen in patients who have achieved initial suppression on an induction regimen and represents a viable treatment simplification strategy.

aDivision of Infectious Diseases, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

bUniversity of Colorado, Rose Medical Center, Denver, Colorado, USA

cOrlando Immunology Center, Orlando, Florida, USA

dSouthwest Infectious Disease Associates, Dallas, Texas, USA

eClinique Medicale L'Actuel, Montreal, Quebec, Canada

fGlaxoSmithKline, USA

gViiV Healthcare, Research Triangle Park, North Carolina, USA.

Received 15 January, 2010

Revised 29 April, 2010

Accepted 6 May, 2010

Correspondence to Kathleen E. Squires, MD, Division of Infectious Diseases, Jefferson Medical College, Thomas Jefferson University, 211 South 9th Street, Suite # 210, Philadelphia, PA 19107, USA. Tel: +1 215 503 8575; fax: +1 215 503 2624; e-mail: kathleen.squires@jefferson.edu

© 2010 Lippincott Williams & Wilkins, Inc.