Background: Previous studies have shown that combination therapy with lamivudine 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 CD4 counts of 25-250/microL.
Methods: Eligible patients receiving zidovudine monotherapy or zidovudine plus zalcitabine or didanosine combination therapy were assigned 52 weeks of treatment with the addition of placebo, lamivudine (150 mg twice a day), or lamivudine (150 mg twice a day) 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 terminated following the second interim analysis because of a highly significant reduction in progression to AIDS or death in the patients treated 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 also seen (p = 0.0007, relative hazard 0.40 [0.23-0.69]). Significantly fewer patients in the lamivudine group than in the placebo group required hospital admission, unscheduled visits, or prescribed medications for HIV-related events. There were no differences in the frequency or severity of clinical or laboratory toxicities between the treatment groups.
Interpretation: The addition of lamivudine to zidovudine-containing treatment regimens significantly slowed the progression of HIV disease and improved survival. However, it is unlikely that this combination alone would be sufficient to achieve long-term complete suppression of viral replication in all patients.