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, Stephsn W. Lagakos, Janet M. Grimes, Daniel S. Stein, James Rooney, Tze Chiang Meng, Margaret A Fischl, Ann C. Collier, John P. Phair, Martin S. Hirsch, W. David Hardy, Henry H. Balfour, Richard C. Reichman

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Abstract

Background. The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine 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, starting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was offered when CD4 cell counts fell below 500 per cubic millimeter. The study end points included overall survival, 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: 547 in the deferred-therapy group, 549 in the group receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg group. The subjects were followed forup to 6.5 years (group medians, 4.8, 4.8, and 4.9, respectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-dose groups (81 cases of progression to 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 both immediate-therapy groups than in the deferred-therapy group (P<0.001 for both). Adverse effects were uncommon, and before the study modification their incidence was similar among the treatment groups, but severe anemia and granulocytopenia were more frequent in the 1500-mg group than in the deferred-therapy group (P<0.001). Conclusions. In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalNew England Journal of Medicine
Volume333
Issue number7
DOIs
StatePublished - Aug 17 1995

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Zidovudine
CD4 Lymphocyte Count
Group Psychotherapy
HIV
Acquired Immunodeficiency Syndrome
Survival
Virus Diseases
Therapeutics
Agranulocytosis
Poisons
Anemia
Placebos
Incidence
Population

ASJC Scopus subject areas

  • Medicine(all)

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A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. / Volberding, Paul A.; Lagakos, Stephsn W.; Grimes, Janet M.; Stein, Daniel S.; Rooney, James; Meng, Tze Chiang; Fischl, Margaret A; Collier, Ann C.; Phair, John P.; Hirsch, Martin S.; Hardy, W. David; Balfour, Henry H.; Reichman, Richard C.

In: New England Journal of Medicine, Vol. 333, No. 7, 17.08.1995, p. 401-407.

Research output: Contribution to journalArticle

Volberding, PA, Lagakos, SW, Grimes, JM, Stein, DS, Rooney, J, Meng, TC, Fischl, MA, Collier, AC, Phair, JP, Hirsch, MS, Hardy, WD, Balfour, HH & Reichman, RC 1995, 'A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter', New England Journal of Medicine, vol. 333, no. 7, pp. 401-407. https://doi.org/10.1056/NEJM199508173330701
Volberding, Paul A. ; Lagakos, Stephsn W. ; Grimes, Janet M. ; Stein, Daniel S. ; Rooney, James ; Meng, Tze Chiang ; Fischl, Margaret A ; Collier, Ann C. ; Phair, John P. ; Hirsch, Martin S. ; Hardy, W. David ; Balfour, Henry H. ; Reichman, Richard C. / A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter. In: New England Journal of Medicine. 1995 ; Vol. 333, No. 7. pp. 401-407.
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title = "A comparison of immediate with deferred zidovudine therapy for asymptomatic HIV-infected adults with CD4 cell counts of 500 or more per cubic millimeter",
abstract = "Background. The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine 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, starting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was offered when CD4 cell counts fell below 500 per cubic millimeter. The study end points included overall survival, 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: 547 in the deferred-therapy group, 549 in the group receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg group. The subjects were followed forup to 6.5 years (group medians, 4.8, 4.8, and 4.9, respectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-dose groups (81 cases of progression to 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 both immediate-therapy groups than in the deferred-therapy group (P<0.001 for both). Adverse effects were uncommon, and before the study modification their incidence was similar among the treatment groups, but severe anemia and granulocytopenia were more frequent in the 1500-mg group than in the deferred-therapy group (P<0.001). Conclusions. In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.",
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AU - Volberding, Paul A.

AU - Lagakos, Stephsn W.

AU - Grimes, Janet M.

AU - Stein, Daniel S.

AU - Rooney, James

AU - Meng, Tze Chiang

AU - Fischl, Margaret A

AU - Collier, Ann C.

AU - Phair, John P.

AU - Hirsch, Martin S.

AU - Hardy, W. David

AU - Balfour, Henry H.

AU - Reichman, Richard C.

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N2 - Background. The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine 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, starting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was offered when CD4 cell counts fell below 500 per cubic millimeter. The study end points included overall survival, 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: 547 in the deferred-therapy group, 549 in the group receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg group. The subjects were followed forup to 6.5 years (group medians, 4.8, 4.8, and 4.9, respectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-dose groups (81 cases of progression to 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 both immediate-therapy groups than in the deferred-therapy group (P<0.001 for both). Adverse effects were uncommon, and before the study modification their incidence was similar among the treatment groups, but severe anemia and granulocytopenia were more frequent in the 1500-mg group than in the deferred-therapy group (P<0.001). Conclusions. In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.

AB - Background. The clinical benefits of zidovudine remain unproved in patients with asymptomatic human immunodeficiency virus (HIV) infection when CD4 cell counts exceed 500 per cubic millimeter. We compared zidovudine 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, starting immediately). In 1989, the study was modified so that open-label treatment with 500 mg of zidovudine per day (deferred therapy) was offered when CD4 cell counts fell below 500 per cubic millimeter. The study end points included overall survival, 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: 547 in the deferred-therapy group, 549 in the group receiving 500 mg of zidovudine immediately, and 541 in the 1500-mg group. The subjects were followed forup to 6.5 years (group medians, 4.8, 4.8, and 4.9, respectively). There was no significant difference in AIDS-free survival in the deferred-therapy group as compared with the low-dose or high-dose groups (81 cases of progression to 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 both immediate-therapy groups than in the deferred-therapy group (P<0.001 for both). Adverse effects were uncommon, and before the study modification their incidence was similar among the treatment groups, but severe anemia and granulocytopenia were more frequent in the 1500-mg group than in the deferred-therapy group (P<0.001). Conclusions. In asymptomatic, HIV-infected adults with 500 or more CD4 cells per cubic millimeter, treatment with zidovudine slows the decline in the CD4 cell count but does not significantly prolong either AIDS-free or overall survival. These results do not encourage the routine use of zidovudine monotherapy in this population.

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