Twice-Daily Trizivir versus Combivir-Abacavir in Antiretroviral-Experienced Adults with Human Immunodeficiency Virus-1 Infection: A Formulation-Switch Trial

• Published in: Pharmacotherapy 2003-11, Vol.23 (11), p.1432-1440
• Main Authors: Fischl, Margaret A., Burnside Jr, Alfred F., Farthing, Charles F., Thompson, Melanie A., Bellos, Nicholaos C., Williams, Vanessa C., Kauf, Teresa L., Wannamaker, Paul G., Shaefer, Mark S.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis of Variance; Anti-HIV Agents - administration & dosage; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chemistry, Pharmaceutical; Confidence Intervals; Dideoxynucleosides - administration & dosage; Drug Administration Schedule; Drug Combinations; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV-1 - drug effects; HIV-1 - metabolism; Human immunodeficiency virus 1; Humans; Lamivudine - administration & dosage; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; RNA, Viral - blood; Zidovudine - administration & dosage
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1592/phco.23.14.1432.31944

Study 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. Design. Randomized, open‐label, parallel‐group, multicenter, formulation‐switch study. Setting. Twenty seven outpatient treatment sites. Patients. 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. Intervention. Patients were randomized 1:1 to Trizivir (97 patients) or Combivir‐ABC (98) for 24 weeks. Measurements and Main 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. Conclusion. Trizivir was clinically equivalent to Combivir‐ABC and may be substituted for the latter to simplify treatment and reduce pill burden.