Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study.
BACKGROUND
Antiretroviral therapy is complicated by drug interactions and contraindications. Novel regimens are needed.


METHODS
This open label study randomly assigned treatment-naive, human immunodeficiency virus (HIV)-infected subjects to receive tenofovir-emtricitabine with efavirenz (Arm I), with ritonavir-boosted atazanavir (Arm II), or with zidovudine/abacavir (Arm III). Pair-wise comparisons of differences in time-weighted mean change from baseline plasma HIV-RNA to week 48 formed the primary analysis. Treatment arms were noninferior if the upper limit of the 95% confidence interval (CI) was <0.5 log(10) copies/mL. Secondary objectives included virologic, immunologic and safety end points.


RESULTS
The intention-to-treat population comprised 322 patients (Arm I, n = 114; Arm II, n = 105; and Arm III, n = 103). Noninferiority for the primary end point was established. Analysis for superiority showed that Arm III was significantly less potent than Arm I (-0.20 log(10) copies/mL; 95% CI, -0.39 to -0.01 log(10) copies/mL; P = .038). The proportions of patients on each of Arm I (95%) and Arm II (96%) with <200 copies/mL were not different (P = .75), but the percentage of patients in Arm III with <200 copies/mL (82%) was significantly lower (P = .005). CD4+ cell counts did not differ. Serious adverse events were more frequent in Arm III (n = 30) than in Arm I or Arm II (n = 15 for each; P = .062).


CONCLUSIONS
A novel quadruple nucleo(t)side combination demonstrated significantly less suppression of HIV replication, compared with the suppression demonstrated by standard antiretroviral therapy regimens, although it did meet the predetermined formal definition of noninferiority. Secondary analyses indicated statistically inferior virologic and safety performance. Efavirenz and ritonavir-boosted atazanavir arms were equivalent in viral suppression and safety.
Puls
Rebekah L
RL
National Centre in HIV Epidemiology and Clinical Research, Faculty of Medicine, University of New South Wales, 45 Beach St, Coogee, New South Wales, Australia, 2034. rpuls@nchecr.unsw.edu.au
Srasuebkul
Preeyaporn
P
Petoumenos
Kathy
K
Boesecke
Christoph
C
Duncombe
Chris
C
Belloso
Waldo H
WH
Molina
Jean-Michel
JM
Li
Lin
L
Avihingsanon
Anchalee
A
Gazzard
Brian
B
Cooper
David A
DA
Emery
Sean
S
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz