Efficacy, safety, and adherence with a twice-daily combination lamivudine/zidovudine tablet formulation, plus a protease inhibitor, in HIV infection

Objective: A randomized, open-label, multicenter study to establish clinica l equivalence (non-inferiority) of a regimen employing a lamivudine 150mg/z idovudine 300 mg combination tablet, administered twice daily, plus a marke ted protease inhibitor, compared with a conventional regimen of 150 mg lami vudine twice daily, 600 mg zidovudine daily acid a protease inhibitor, in a ntiretroviral-experienced patients infected with HIV-1. Patients: Adults who were seropositive for HIV-1 infection with plasma HIV- I RNA levels ( 10 000 copies/ml (Roche Amplicor polymerase chain reaction a ssay, lower limit of quantitation (LLOQ) 400 copies/ml) and CD4+ cell count s greater than or equal to 300 x 10(6)/l). All patients had been receiving the conventional lamivudine/zidovudine/protease inhibitor regimen for great er than or equal to 10 weeks immediately prior to the study. Intervention: Patients were randomized to the conventional regimen (n = 113 ) or combination tablet regimen (n = 110) For 16 weeks. The primary study e ndpoint was treatment failure, defined as an increase in HIV-1 RNA greater than or equal to 0.5 log(10) above baseline in patients with viral load > L LOQ at randomization and as HIV-1 RNA increasing to greater than or equal t o 1250 copies/ml in patients with viral load < LLOQ at randomization. Results: The combination tablet regimen was associated with a 3.5% greater success rate than the conventional regimen (96.4 versus 92.9%), with four a nd eight patients failing treatment due to increases in HIV-1 RNA levels, r espectively. The lower limit of the associated confidence interval for the difference was -2.4%, which was well within the -10% margin predefined as c linically unimportant. This establishes the clinical equivalence (non-infer iority) of the combination tablet regimen to the conventional regimens rega rding virologic response. The combination tablet and conventional regimens were similar with respect to percentage of patients maintaining HIV-1 RNA l evels < LLOQ at the end of study or improving from baseline to undetectabil ity (94 versus 91%; P = 0.063), overall incidence of drug-related adverse e vents (21 Versus 19%) (P = 0.868), and mean area under the curve for CD4+ c ell counts [treatment difference, 5.9 cells (95% confidence interval, -15.8 to 27.6 x 10(6) cells/ 1)]. A self-reported adherence questionnaire indica ted that patients in the combination tablet group were less likely to miss doses of nucleoside analogue medication at weeks 8 (P = 0.007) and 16(P = 0 .046). Conclusions: The combination lamivudine/zidovudine tablet/protease inhibito r regimen is clinically equivalent (non-inferior) to the conventional regim en with respect to virologic response and may offer adherence advantages. ( C) 2000 Lippincott Williams & Wilkins.