Disease progression in HIV-infected patients treated with stavudine vs. zidovudine

Justice, Amy C; Stein, Daniel S; Fusco, Gregory P; Sherrill, Beth H; Fusco, Jennifer S; Danehower, Susan C; Becker, Stephen L; Hansen, Nellie I; Graham, Neil M.H; the CHORUS Program Team,

doi:10.1016/S0895-4356(03)00245-2

« Previous Next »Journal of Clinical Epidemiology
Volume 57, Issue 1 , Pages 89-97, January 2004

Disease progression in HIV-infected patients treated with stavudine vs. zidovudine

Amy C Justice
- Yale University, New Haven, CT, USA
- West Haven Veterans Affairs Healthcare System, 950 Campbell Avenue, 11-ACSLG, West Haven, CT 06516, USA
- Corresponding author. Tel.: 412-688-6957; fax: 412-688-6916.
Daniel S Stein
- ^cGlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA
Gregory P Fusco
- ^cGlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA
Beth H Sherrill
- Research Triangle Institute, P.O. Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA
Jennifer S Fusco
- ^cGlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA
Susan C Danehower
- ^cGlaxoSmithKline Inc., 5 Moore Drive, Research Triangle Park, NC 27709, USA
Stephen L Becker
- Pacific Horizon Medical Group, 2351 Clay Street, Suite 412, San Francisco, CA 94115, USA
Nellie I Hansen
- Research Triangle Institute, P.O. Box 12194, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA
Neil M.H Graham
- Virco Laboratories Inc., 2505 Meridian Parkway, Suit 350, Durham, NC 27713, USA¹
the CHORUS Program Team

Accepted 18 February 2003.

Abstract

Background and Objectives

This prospective, observational study compared disease progression and death in HIV-1 patients treated with stavudine vs. zidovudine in the Collaborations in HIV Outcomes Research/U.S. (CHORUS) cohort.

Methods

Patients with a first occurrence of CD4 count <500 cells/μL (n=3301) were grouped as: no nucleoside reverse transcriptase inhibitor (NRTI) use; other NRTI without stavudine or zidovudine; stavudine with no zidovudine, with or without other NRTIs; and zidovudine with no stavudine, with or without other NRTIs. The risk for death or disease progression was evaluated in unadjusted analyses and using a Cox proportional hazards model, adjusting for: study site, age, gender, race, route of HIV infection, previous AIDS-defining conditions, number of previous antiretroviral regiments, CD4 count, HIV-1 RNA, and treatment variables. Sensitivity analyses were conducted to determine the sensitivity of the results to major modeling assumptions. A landmark analysis was conducted to determine the absolute difference in time to event.

Results

During a median follow-up of 2.4 years, there were 57 deaths and 348 AIDS-defining conditions in 405 patients. Stavudine treatment compared with zidovudine resulted in a greater percentage of patients with AIDS-defining events (14.5 vs. 10.9%; P=.013), and an increased risk of disease progression (HR=1.30; 95% CI: 1.01,1.7; P=.04). This result was not sensitive to modeling assumptions. Landmark analysis demonstrated an absolute difference in time to 95% event-free survival of 2.7 months for those with a CD4⩽200 cells/μL and 11 months for those 6 months after model entry.

Conclusions

In unadjusted and adjusted analyses of 3301 HIV-1 infected patients, stavudine containing combination therapy was associated with an increased risk of disease progression or death compared to therapy containing zidovudine. Most of the difference was attributable to new cases of wasting.

Keywords: Stavudine, Zidovudine, Disease progression, Longitudinal study, CHORUS, HIV wasting