A Comparison of Immediate with Deferred Zidovudine Therapy for Asymptomatic HIV-Infected Adults with CD4 Cell Counts of 500 or More per Cubic Millimeter
Paul A. Volberding, M.D., Stephen W. Lagakos, Ph.D., Janet M. Grimes, M.S., Daniel S. Stein, M.D., James Rooney, M.D., Tze-Chiang Meng, M.D., Margaret A. Fischl, M.D., Ann C. Collier, M.D., John P. Phair, M.D., Martin S. Hirsch, M.D., W. David Hardy, M.D., Henry H. Balfour, M.D., Richard C. Reichman, M.D., for The AIDS Clinical Trials Group
Background The clinical benefits of zidovudine remain unprovedin patients with asymptomatic human immunodeficiency virus (HIV)infection when CD4 cell counts exceed 500 per cubic millimeter.We compared zidovudine therapy given immediately with deferredtherapy in such subjects.
Methods Beginning in 1987, subjects with asymptomatic HIV infectionand 500 or more CD4 cells per cubic millimeter were randomlyassigned to receive placebo or zidovudine (either 500 or 1500mg per day, starting immediately). In 1989, the study was modifiedso that open-label treatment with 500 mg of zidovudine per day(deferred therapy) was offered when CD4 cell counts fell below500 per cubic millimeter. The study end points included overallsurvival, survival free of the acquired immunodeficiency syndrome(AIDS), toxic effects, and changes in CD4 cell counts.
Results There were 1637 subjects who could be evaluated: 547in the deferred-therapy group, 549 in the group receiving 500mg of zidovudine immediately, and 541 in the 1500-mg group.The subjects were followed for up to 6.5 years (group medians,4.8, 4.8, and 4.9, respectively). There was no significant differencein AIDS-free survival in the deferred-therapy group as comparedwith the low-dose or high-dose groups (81 cases of progressionto AIDS or death vs. 81 and 74, respectively; P = 0.95 and P= 0.13) or in overall survival (51 deaths vs. 47 and 46; P =0.25 and P = 0.16). The decline in CD4 cells was slower in bothimmediate-therapy groups than in the deferred-therapy group(P<0.001 for both). Adverse effects were uncommon, and beforethe study modification their incidence was similar among thetreatment groups, but severe anemia and granulocytopenia weremore frequent in the 1500-mg group than in the deferred-therapygroup (P<0.001).
Conclusions In asymptomatic, HIV-infected adults with 500 ormore CD4 cells per cubic millimeter, treatment with zidovudineslows the decline in the CD4 cell count but does not significantlyprolong either AIDS-free or overall survival. These resultsdo not encourage the routine use of zidovudine monotherapy inthis population.
Source Information
From the University of California, San Francisco (P.A.V.); Harvard University, Boston (S.W.L., J.M.G., M.S.H.); Albany Medical College, Albany, N.Y. (D.S.S.); the Burroughs Wellcome Company, Raleigh, N.C. (J.R.); the University of California, San Diego (T.-C.M.); the University of Miami, Miami (M.A.F.); the University of Washington, Seattle (A.C.C.); Northwestern University, Chicago (J.P.P.); the University of California, Los Angeles (W.D.H.); the University of Minnesota, Minneapolis (H.H.B.); and the University of Rochester, Rochester, N.Y. (R.C.R.).
Address reprint requests to Dr. Volberding at the UCSF AIDS Program, San Francisco General Hospital, 995 Potrero Ave., Bldg. 80, Ward 84, San Francisco, CA 94110.
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