ZIDOVUDINE ALONE OR IN COMBINATION WITH DIDANOSINE OR ZALCITABINE IN HIV-INFECTED PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME OR FEWER THAN 200 CD4 CELLS PER CUBIC MILLIMETER

Background We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) in fection. Methods A total of 1102 patients with the acquired immunodefi ciency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined w ith either didanosine or zalcitabine. Disease progression, survival, t oxic effects, and the CD4 cell response were assessed. Results After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosi ne, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine alone (P=0.24). As compa red with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death o f 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment w ith zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was sim ilar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously re ceived zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and trea tment with zidovudine plus zalcitabine, more neuropathy. The mean incr eases in CD4 cell counts at two months were higher with combination th erapy than with zidovudine alone. Conclusions In patients with advance d HIV infection, combination therapy with zidovudine and either didano sine or zalcitabine is not superior to zidovudine therapy alone. Howev er, these combinations may be more effective than zidovudine monothera py in patients with little or no previous zidovudine treatment.