Safety and activity of zalcitabine and zidovudine combination in HIV-positive people with CD4 cell counts < or = 300 cells/mm3. The Roche M50002 Study Group

We carried out an open-label, single-arm, multicentre 1-year study of the safety and activity of therapy with a zalcitabine-zidovudine combination in 561 patients with CD4 cell counts < or = 300 cells/mm3 who were either established on zidovudine or had not previously received antiretroviral therapy. Additionally, we assessed the impact of baseline characteristics on clinical outcome during therapy. The study used specialist HIV-care centres in Argentina, Belgium, Brazil, Hungary, Italy, Luxembourg, Mexico, Peru, Spain and Venezuela. Participants were regularly assessed for adverse experiences, changes in laboratory values and clinical progression. A total of 561 patients entered the study, with 353 completing 12 months of follow-up. The 492 zidovudine-experienced patients had a mean duration of previous therapy of 18.5 months. No unexpected adverse events were reported. Peripheral neuropathy was observed in 12.7% of patients and was more common in participants with CD4 cell counts < or = 100 cells/mm3 at baseline. Clinical disease progression was significantly associated with lower baseline CD4 cell counts, a history of previous AIDS-defining events and a baseline haemoglobin < 11 g/dl. The median CD4 cell count at baseline was 141.5 cells/mm3, rising to 174 cells/mm3 after 12 weeks and to 148 cells/mm3 at 12 months. In conclusion, zalcitabine-zidovudine combination therapy was found to be well tolerated in this patient population, although patients with CD4 cell counts < or = 100 cells/mm3 were found to require more intensive monitoring for toxicities and disease events. The changes in the CD4 cell count seen in this study and in others provide evidence of the therapeutic activity of this combination.