Twice-daily Trizivir versus Combivir-abacavir in antiretroviral-experienced adults with human immunodeficiency virus-1 infection: a formulation-switch trial.
OBJECTIVE
To establish the clinical equivalence (noninferiority) of one tablet containing abacavir 300 mg-lamivudine 150 mg-zidovudine 300 mg (Trizivir) versus a tablet containing lamivudine 150 mg-zidovudine 300 mg (Combivir) given with one abacavir (ABC) 300-mg tablet, administered twice/day, in antiretroviral-experienced, human immunodeficiency virus (HIV)-1-infected patients.


METHODS
Randomized, open-label, parallel-group, multicenter, formulation-switch study.


METHODS
Twenty seven outpatient treatment sites.


METHODS
Adults with HIV-1 RNA levels of 400 copies/ml or less and CD4+ cell counts above 200 cells/mm3 who had been treated for 16 weeks or more with highly active antiretroviral therapy containing Combivir-ABC.


METHODS
Patients were randomized 1:1 to Trizivir (97 patients) or Combivir-ABC (98) for 24 weeks.


RESULTS
The primary study end point was the proportion of patients who maintained less than a 0.5-log10 increase from baseline in HIV-1 RNA (virologic success) through week 24. Clinical equivalence of the treatments was established if the 95.1% lower confidence limit (LCL) for the difference in proportion of virologic success with Trizivir minus Combivir-ABC was -0.12 or greater. Trizivir was clinically equivalent to Combivir-ABC. The intent-to-treat observed analysis at week 24 with Trizivir and Combivir-ABC showed a similar rate of virologic success (83% [80/97] and 77% [75/98], respectively, 95.1% LCL -0.026), of patients with HIV-1 RNA levels of 400 or fewer copies/ml (99% [82/83] and 93% [77/83], respectively, 95.1% LCL 0.021), and of patients with HIV-1 RNA levels of fewer than 50 copies/ml (89% [74/83] and 77% [64/83], respectively, 95.1% LCL 0.038). The intent-to-treat missing = failure analysis showed comparable results. Changes in CD4+ cell count from baseline, overall mean self-reported adherence (Trizivir 97%, Combivir-ABC 92%), and adverse events did not differ significantly between treatments. No ABC-related hypersensitivity reactions occurred.


CONCLUSIONS
Trizivir was clinically equivalent to Combivir-ABC and may be substituted for the latter to simplify treatment and reduce pill burden.
Fischl
Margaret A
MA
University of Miami, School of Medicine, Department of Medicine, Florida 33136, USA. m.fischl@miami.edu
Burnside
Alfred E
AE
Farthing
Charles E
CE
Thompson
Melanie A
MA
Bellos
Nicholaos C
NC
Williams
Vanessa C
VC
Kauf
Teresa L
TL
Wannamaker
Paul G
PG
Shaefer
Mark S
MS
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D015215:Zidovudine / Q000008:administration & dosage*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; D012367:RNA, Viral; D015215:Zidovudine; D000099227:Abacavir; C418262:abacavir, lamivudine, and zidovudine drug combination; C109078:lamivudine, zidovudine drug combination