COMBINATION AND MONOTHERAPY WITH ZIDOVUDINE AND ZALCITABINE IN PATIENTS WITH ADVANCED HIV DISEASE

Objective: To compare the safety and efficacy of continuing zidovudine therapy with that of zalcitabine alone or zalcitabine and zidovudine used together. Design: A randomized, double-blind, controlled trial. Setting: AIDS Clinical Trials units and National Hemophilia Foundation sites. Patients: 1001 patients with symptomatic human immunodeficiency (HIV) disease and 300 or fewer CD4 cells/mm(3) or asymptomatic HIV disease and 200 or fewer CD4 cells/mm(3) who had tolerated zidovudine therapy for 6 months or more. Intervention: Patients were randomly assigned to receive zidovudine, 600 mg/d; zalcitabine, 2.25 mg/d; or zidovudine, 600 mg/d, and zalcitabine, 2.25 mg/d. Measurements: The primary end point was time to disease progression or death. Results: The median follow-up time was 17.7 months. The estimated 72-month event-free rates were 70%, 67%, and 73%, respectively, for the zidovudine, zalcitabine, and combination groups (P = 0.26). A trend analysis showed significantly lower progression rates for combination therapy compared with zidovudine therapy as the pretreatment CD4 cell count increased (P = 0.027). For patients with 150 or more CD4 cells/ mm(3), those receiving combination therapy were less likely to have disease progression or to die than were those receiving zidovudine (relative risk, 0.51; 95% Cl, 0.28 to 0.93; P = 0.029). We observed no difference between the zalcitabine and zidovudine groups (relative risk, 0.74; Cl, 0.40 to 1.36; P = 0.33). For patients with 50 to 150 CD4 cells/mm(3) or fewer than 50 CD4 cells/mm(3), we found no differences among the treatment groups (P = 0.69 and P = 0.57, respectively). Severe toxic effects occurred less frequently among patients with 150 or more CD4 cells/mm(3). Conclusions: We found no overall benefits of zalcitabine used alone or with zidovudine. However, a trend analysis suggested a better outcome for combination therapy compared with zidovudine as the pretreatment CD4 cell count increased.