RANDOMIZED TRIAL OF ADDITION OF LAMIVUDINE OR LAMIVUDINE PLUS LOVIRIDE TO ZIDOVUDINE-CONTAINING REGIMENS FOR PATIENTS WITH HIV-1 INFECTION - THE CAESAR TRIAL

Background Previous studies have shown that combination therapy with l amivudine plus zidovudine causes pronounced and sustained increases in CD4 counts and reductions in viral load in individuals infected with HIV-1. We assessed the clinical benefit of the addition of lamivudine to zidovudine-based regimens in patients infected with HIV-1 who had C D4 counts of 25-250/mu L. Methods Eligible patients receiving zidovudi ne monotherapy or zidovudine plus zalcitabine or didanosine combinatio n therapy were assigned 52 weeks of treatment with the addition of pla cebo, lamivudine (150 mg twice a day), or lamivudine (150 mg twice a d ay) plus loviride (100 mg three times a day). Patients were unaware of type of treatment allocated. The primary endpoint was progression to a new protocol-defined AIDS event or death. Findings The study was ter minated following the second interim analysis because of a highly sign ificant reduction in progression to AIDS or death in the patients trea ted with lamivudine rather than placebo. In the final analysis of 1840 patients, progression had occurred in 95 (20%) of 471 placebo-treated patients, 86 (9%) of 907 lamivudine-treated patients, and 42 (9%) of 462 patients who received lamivudine plus loviride (p<0.0001, relative hazard 0.42 [95% CI 0.32-0.57]). A significant survival benefit was a lso seen (p=0.0007, relative hazard 0.40 [0.23-0.69]). Significantly f ewer patients in the lamivudine group than in the placebo group requir ed hospital admission, unscheduled visits, or prescribed medications f or HIV-related events. There were no differences in the frequency or s everity of clinical or laboratory toxicities between the treatment gro ups. Interpretation The addition of lamivudine to zidovudine-containin g treatment regimens significantly slowed the progression of HIV disea se and improved survival. However, it is unlikely that this combinatio n alone would be sufficient to achieve long-term complete suppression of viral replication in all patients.