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.
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.


CONCLUSIONS
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.
Squires
Kathleen E
KE
Division of Infectious Diseases, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. kathleen.squires@jefferson.edu
Young
Benjamin
B
Dejesus
Edwin
E
Bellos
Nicholaos
N
Murphy
Daniel
D
Zhao
Henry H
HH
Patel
Lisa G
LG
Ross
Lisa L
LL
Wannamaker
Paul G
PG
Shaefer
Mark S
MS
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000099227:Abacavir
D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D009842:Oligopeptides; D011725:Pyridines; D019438:Ritonavir; D000099227:Abacavir