Triple nucleoside treatment with abacavir plus the lamivudine/ zidovudine combination tablet (COM) compared to indinavir/COM in antiretroviral therapy-naïve adults: results of a 48-week open-label, equivalence trial (CNA3014)

• Published in: Current medical research and opinion 2004-07, Vol.20 (7), p.1103-1114
• Main Authors: Vibhagool, Asda, Cahn, Pedro, Schechter, Mauro, Smaill, Fiona, Soto-Ramirez, Luis, Carosi, Giampiero, Montroni, Maria, Pharo, Cristina E., Jordan, Jamie C., Thomas, Nicola E., Pearce, Gill
• Format: Article
• Language: English
• Subjects: Abacavir; Adult; Antiretroviral Therapy, Highly Active; Combination antiretroviral therapy; Combination tablet; Dideoxynucleosides - administration & dosage; Dideoxynucleosides - pharmacology; Dideoxynucleosides - therapeutic use; Drug Therapy, Combination; Female; HIV Infections - drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - pharmacology; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; Humans; Indinavir; Indinavir - administration & dosage; Indinavir - pharmacology; Indinavir - therapeutic use; Lamivudine - administration & dosage; Lamivudine - pharmacology; Lamivudine - therapeutic use; Lamivudine/zidovudine; Male; Patient Compliance; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; RNA - drug effects; Surveys and Questionnaires; Therapeutic Equivalency; Treatment Outcome; Zidovudine - administration & dosage; Zidovudine - pharmacology; Zidovudine - therapeutic use
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/030079904125004006

SUMMARY Objective: An equivalence (non-inferiority) trial comparing antiviral response, tolerability, and adherence with a triple nucleoside regimen containing abacavir 300 mg (ABC) plus a lamivudine 150-mg/zidovudine 300-mg combination tablet (COM) twice daily vs. a regimen containing the protease inhibitor indinavir (IDV) 800 mg three times daily plus COM twice daily (IDV/COM) in antiretroviral-naïve, HIV-infected patients. Methods: Adult patients with plasma HIV-1 RNA levels ≥ 5000 copies/mL and CD4+ cell counts ≥ 100 cells/mm3 were randomized to receive open-label ABC/COM (n = 169) or IDV/COM (n = 173) for 48 weeks. The intent-to-treat (ITT) population was the primary population evaluated. ITT: switch/missing equals failure (ITT: S/M = F) and as-treated (AT) analyses were used for assessing the proportion of patients achieving plasma HIV-1 RNA level < 400 and < 50 copies/mL at each clinic visit. In the ITT: S/M = F analysis, patients who switched treatment or had missing values were considered treatment failures; the AT analysis examined virologic data only while patients received study treatment. ABC/COM was considered equivalent (non-inferior) to IDV/COM if the lower limit of the 95% confidence intervals (CIs) about the difference in proportions of ABC/COM- vs. IDV/COM-treated patients attaining plasma HIV-1 RNA < 400 copies/mL exceeded -15% at week 48. Results: The study population was diverse with respect to ethnicity (38% Asian, 27% Hispanic, 28% white, 3% black, 4% other) and gender (39% women, 61% men). Baseline median HIV-1 RNA was 4.80 log10 copies/mL and CD4+ cell count was 315 cells/mm3. ABC/COM met the criterion of equivalence to IDV/COM. In the ITT: S/M = F analysis at Week 48, a greater proportion of ABC/COM-treated patients achieved HIV-1 RNA < 400 copies/mL (66% [109/164] vs. 50% [82/165]; treatment difference 16.6%, 95% CI (6.0, 27.2), p = 0.002) and HIV-1 RNA < 50 copies/mL (60% [99/164] vs. 50% [83/165]; treatment difference 9.6%, 95% CI [-1.1, 20.2]), whereas the AT analysis showed similar proportions achieving these endpoints (< 400 copies/mL: 85 vs. 83%; < 50 copies/mL: 79 vs 81%). Comparable proportions of patients with screening HIV-1 RNA values > 100 000 copies/mL achieved HIV-1 RNA < 400 copies/mL (ABC/COM: 60% [35/58]; IDV/COM: 51% [33/65]; treatment difference 9.6%, 95% CI [-7.9, 27.1]; ITT: S/M = F analysis). A significantly greater proportion taking ABC/COM were ≥ 95% adherent (72% [109/151] vs. 45% [70/154] with IDV/COM,