A COMPARISON OF IMMEDIATE WITH DEFERRED ZIDOVUDINE THERAPY FOR ASYMPTOMATIC HIV-INFECTED ADULTS WITH CD4 CELL COUNTS OF 500 OR MORE PER CUBIC MILLIMETER

Background. The clinical benefits of zidovudine remain unproved in pat ients with asymptomatic human immunodeficiency virus (HIV) infection w hen CD4 cell counts exceed 500 per cubic millimeter. We compared zidov udine therapy given immediately with deferred therapy in such subjects . Methods. Beginning in 1987, subjects with asymptomatic HIV infection and 500 or more CD4 cells per cubic millimeter were randomly assigned to receive placebo or zidovudine (either 500 or 1500 mg per day, star ting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was off ered when CD4 cell counts fell below 500 per cubic millimeter. The stu dy end points included overall survival, survival free of the acquired immunodeficiency syndrome (AIDS), toxic effects, and changes in CD4 c ell counts. Results. There were 1637 subjects who could be evaluated: 547 in the deferred-therapy group, 549 in the group receiving 500 mg o f zidovudine immediately, and 541 in the 1500-mg group. The subjects w ere followed for up to 6.5 years (group medians, 4.8, 4.8, and 4.9, re spectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-d ose groups (81 cases of progression to AIDS or death vs. 81 and 74, re spectively; P = 0.95 and P = 0.13) or in overall survival (51 deaths v s. 47 and 46; P = 0.25 and P = 0.16). The decline in CD4 cells was slo wer in both immediate-therapy groups than in the deferred-therapy grou p (P<0.001 for both). Adverse effects were uncommon, and before the st udy modification their incidence was similar among the treatment group s, but severe anemia and granulocytopenia were more frequent in the 15 00-mg group than in the deferred-therapy group (P<0.001). Conclusions. In asymptomatic, HIV-infected adults with 500 or more CD4 cells per c ubic millimeter, treatment with zidovudine slows the decline in the CD 4 cell count but does not significantly prolong either AIDS-free or ov erall survival. These results do not encourage the routine use of zido vudine monotherapy in this population.