Zidovudine monotherapy versus zidovudine plus zalcitabine combination therapy in HIV-positive persons with CD4 cell counts 300-500 cells/mm3: a double-blind controlled trial. The M50003 Study Group Coordinating and Writing Committee.

OBJECTIVE: To assess the safety and clinical and immunological activity of zalcitabine/zidovudine combination therapy compared with zidovudine monotherapy in persons with no or limited antiretroviral experience and CD4 counts of 300-500 cells/mm3. DESIGN AND SETTING: A double-blind controlled multi-centre study conducted in specialist human immunodeficiency virus (HIV) care centres in Spain, Portugal and Australia. Participants were randomized at study entry to zidovudine (200 mg three times daily) plus zalcitabine (0.75 mg three times daily) or matched placebo. The primary end point was the proportion of patients with CD4 above baseline value at 24 months. The secondary end points were time to AIDS/death, quality of life (by MOS-30) and safety. RESULTS: The study was terminated prematurely following the results of the Delta and ACTG 175 studies. Two-hundred and fifty-six patients entered the protocol of whom all but 15 were treatment naive. One hundred and twenty-seven patients commenced zidovudine and 129 commenced a combination of zidovudine/zalcitabine. The median duration of follow-up was 634 days with a median time on blinded therapy of 500 days. Using the last available CD4 count data, 32.4% randomized to zidovudine and 65.1% randomized to zidovudine/zalcitabine remained above baseline at study close (P or = 300 cells/mm3 inclusion of zalcitabine with zidovudine does not increase the incidence of adverse events or adversely affect quality of life.