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
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: firstname.lastname@example.org