CLINICAL EFFICACY OF MONOTHERAPY WITH STAVUDINE COMPARED WITH ZIDOVUDINE IN HIV-INFECTED, ZIDOVUDINE-EXPERIENCED PATIENTS - A RANDOMIZED, DOUBLE-BLIND, CONTROLLED TRIAL

Background: Stavudine is a promising antiretroviral agent, but its cli nical efficacy has not been determined. Objective: To evaluate the cli nical effect of stavudine (2',3'-didehydro-3'-deoxythymidine) monother apy in patients with human immunodeficiency virus (HIV) infection. Des ign: Randomized, controlled, double-blind trial. Setting: 56 outpatien t clinics in private practices, universities, and contract research or ganizations in the United States, France, and Italy. Patients: 822 HIV -infected adults who had 50 to 500 CD4(+) cells/mm(3) and had previous ly received at least 6 months of zidovudine treatment. Intervention: M onotherapy with peroral stavudine capsules or peroral zidovudine capsu les. Measurements: The primary end point was clinical progression, whi ch was defined as all occurrences of acquired immunodeficiency syndrom e (AIDS)-defining events or death. Results: Patients receiving stavudi ne reached clinical end points at a rate of 26 per 100 person-years, c ompared 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 zidovudin e group, but the comparison was not statistically significant (relativ e risk, 0.74 [CI, 0.53 to 1.02]; P = 0.066). The benefit of stavudine therapy was seen in all CD4(+) cell strata (less than or equal to 100 cells/mm(3), 101 to 300 cells/mm(3), and >300 cells/mm(3)) and clinica l stages of HIV disease (asymptomatic, symptomatic, and AIDS). Four we eks after treatment began, CD4(+) cell counts were 30 cells/mm(3) high er in the stavudine group than in the zidovudine group; this differenc e was sustained for 96 weeks (P < 0.001). Nausea and vomiting were mor e common in patients receiving zidovudine (P < 0.01), and neuropathy o ccurred more frequently in those receiving stavudine (12% in the stavu dine group compared with 4% in the zidovudine group; Pc 0.001). Neurop athy 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 pr ogression 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 im portant agent to consider for trials of combination chemotherapy.