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Clinical Efficacy of Monotherapy with Stavudine Compared with Zidovudine in HIV-Infected, Zidovudine-Experienced Patients: A Randomized, Double-Blind, Controlled Trial

Spotswood L. Spruance, MD; Andrew T. Pavia, MD; John W. Mellors, MD; Robert Murphy, MD; Joseph Gathe Jr., MD; Edward Stool, MD; Joseph G. Jemsek, MD; Pierre Dellamonica, MD; Anne Cross, PhD; and Lisa Dunkle, MD
[+] Article and Author Information

For the Bristol-Myers Squibb Stavudine/019 Study Group. Grant Support: In part by grants from Bristol-Myers Squibb Co. Requests for Reprints: Spotswood L. Spruance, MD, Health Sciences AIDS Center, Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, UT 84132. Current Author Addresses: Drs. Spruance and Pavia: Health Sciences AIDS Center, Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, UT 84132.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;126(5):355-363. doi:10.7326/0003-4819-126-5-199703010-00003
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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, CD4+ 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.

Figures

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Figure 1.
Kaplan-Meier estimate of the distribution of time to clinical progression (all acquired immunodeficiency syndrome-defining events or death) by treatment group. Top.Bottom.333

Results for all study patients. Results stratified by the three protocol-defined strata of CD4+ cell count at baseline (≤ 100 cells/mm , 101 to 300 cells/mm , and >300 cells/mm ).

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Figure 2.
Kaplan-Meier estimate of the distribution of time to treatment failure (first acquired immunodeficiency syndrome-defining event, death, or sustained decline in CD4+ cell count to ≤ 50% of baseline level) by treatment group. Top.Bottom.333

Results for all study patients. Results stratified by the three protocol-defined strata of CD4+ cell count at baseline (≤ 100 cells/mm , 101 to 300 cells/mm , and >300 cells/mm ).

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Figure 3.
Mean change in CD4+ cell count from baseline values by treatment group.

Bars represent SEs.

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