Clinical efficacy of monotherapy with stavudine compared with zidovudine in HIV-infected, zidovudine-experienced patients. A randomized, double- blind, controlled trial

Spotswood L. Spruance*, Andrew T. Pavia, John W. Mellors, Robert Murphy, Joseph Gathe, Edward Stool, Joseph G. Jemsek, Pierre Dellamonica, Anne Cross, Lisa Dunkle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Background: Stavudine is a promising antiretroviral agent, but its clinical efficacy has not been determined. Objective: To evaluate the clinical effect of stavudine (2',3'-didehydro-3'-deoxythymidine) monotherapy in patients with human immunodeficiency virus (HIV) infection. Design: Randomized, controlled, double-blind trial. Setting: 56 outpatient clinics in private practices, universities, and contract research organizations in the United States, France, and Italy. Patients: 822 HIV-infected adults who had 50 to 500 CD4+ cells/mm3 and had previously received at least 6 months of zidovudine treatment. Intervention: Monotherapy with peroral stavudine capsules or peroral zidovudine capsules. Measurements: The primary end point was clinical progression, which was defined as all occurrences of acquired immunodeficiency syndrome (AIDS)-defining events or death. Results: Patients receiving stavudine reached clinical end points at a rate of 26 per 100 person-years, compared with 32 per 100 person-years for patients receiving zidovudine (relative risk, 0.75 [95% CI, 0.58 to 0.98]; P = 0.03). The risk for death alone was 26% lower in the stavudine group than in the zidovudine group, but the comparison was not statistically significant (relative risk, 0.74 [CI, 0.53 to 1.02]; P = 0.066). The benefit of stavudine therapy was seen in all CD4+ cell strata (≤ 100 cells/mm3, 101 to 300 cells/mm3, and >300 cells/mm3) and clinical stages of HIV disease (asymptomatic, symptomatic, and AIDS). Four weeks after treatment began, CO4+ cell counts were 30 cells/mm3 higher in the stavudine group than in the zidovudine group; this difference was sustained for 96 weeks (P < 0.001). Nausea and vomiting were more common in patients receiving zidovudine (P < 0.01), and neuropathy occurred more frequently in those receiving stavudine (12% in the stavudine group compared with 4% in the zidovudine group; P < 0.001). Neuropathy resolved completely in many patients (63%) after interruption of stavudine treatment; these patients could resume stavudine therapy at a lower dose. Conclusions: Stavudine was well tolerated and delayed progression of HIV disease in patients who had previously received 6 or more months of zidovudine treatment. Benefits were apparent in all CD4+ cell strata and clinical stages of HIV disease. Stavudine is an important agent to consider for trials of combination chemotherapy.

Original languageEnglish (US)
Pages (from-to)355-363
Number of pages9
JournalAnnals of internal medicine
Volume126
Issue number5
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Internal Medicine

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