Disease progression in HIV-infected patients treated with stavudine vs. zidovudine.
OBJECTIVE
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/microL (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< or =200 cells/microL 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.
Justice
Amy C
AC
Yale University, New Haven, CT, USA. AmyJustice@med.va.gov
Stein
Daniel S
DS
Fusco
Gregory P
GP
Sherrill
Beth H
BH
Fusco
Jennifer S
JS
Danehower
Susan C
SC
Becker
Stephen L
SL
Hansen
Nellie I
NI
Graham
Neil M H
NM
D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D016208:Databases, Factual; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D019247:HIV Wasting Syndrome / Q000175:diagnosis; D006801:Humans; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D018119:Stavudine