Didanosine, lamivudine, and efavirenz versus zidovudine, lamivudine, and efavirenz for the initial treatment of HIV type 1 infection:: Final analysis (48 weeks) of a prospective, randomized, noninferiority clinical trial, GESIDA 3903

Background. The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials. Methods. We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine- zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log(10) or >= 5.0 log(10) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis. Results. Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/ EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log 10 copies/mL, and median CD4(+) cell count was 208 cells/mL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of < 50 copies/mL (treatment difference, 7.1%; 95% confidence interval, -2.39% to 16.59%). Fourteen patients (8%) in the COM/EFV arm and 26 patients (14%) in the ddI/3TC/ EFV arm discontinued the study medication because of adverse events (P=.046). One patient (1%) in the ddI/3TC/ EFV arm and 11 patients (6%) in the COM/EFV Parm discontinued medication because of hematological toxicity (P=.003). Conclusions. At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity.