Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. HIV Protocol C91-253 Study Team.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):245-54. Unique Identifier : AIDSLINE MED/99174790
Krown SE; Aeppli D; Balfour HH Jr; Department of Medicine, Memorial Sloan-Kettering Cancer Center; and Cornell University Medical College, New York, New York 10021,; USA.

Abstract: OBJECTIVES: To compare, in a community-based therapeutic setting, the safety, tolerance, and efficacy of combination therapy with recombinant interferon-alpha2b (rIFN-alpha2b) and zidovudine (ZDV) to ZDV monotherapy. DESIGN: Open-label, two-armed, randomized study. PATIENTS AND METHODS: Asymptomatic or minimally symptomatic HIV-infected adults without an AIDS-defining illness, a CD4 count of 200 to 500 cells/microl, and < or = 6 months of prior ZDV therapy received ZDV 100 mg orally five times daily. Patients randomized to rIFN-alpha2b received 3 million IU subcutaneously three times weekly for 2 weeks and 5 million IU three times weekly thereafter. The groups were compared with respect to adverse events (AEs), dosing modifications, treatment discontinuation, clinical endpoints and changes in CD4 count. A virology substudy compared the treatments with respect to HIV viral load and development of ZDV resistance. RESULTS: Between October, 1991 and January, 1993, 139 patients were randomized to combination therapy and 117 to ZDV alone. Of AEs reported at any grade, fatigue, myalgias, and sweating occurred significantly more often with combination therapy (p < .001). Study subjects receiving combination therapy showed modest but significantly greater weight loss (p = .0001), a significantly higher frequency of any abnormal laboratory test result (p = .002), neutropenia (p = .002), and leukopenia (p = .02), and also required dosage reduction for hematologic toxicity significantly more often (p < .05) than those in the ZDV monotherapy arm. No statistically significant differences were found between the groups with respect to development of specific AIDS-defining events, overall event rate, time to events, or change in performance status or CD4+ counts, or percentages or development of ZDV resistance. Viral burden, reflected by serum p24 antigen and quantitative peripheral blood mononuclear cell (PBMC) microcultures, was greater at baseline in the combination therapy group. Baseline SI phenotype predicted progression to AIDS (p = .004, chi2), whereas intermediate susceptibility to ZDV predicted development of ZDV resistance (p < .005, chi2). The annual rate of development of phenotypic resistance to ZDV was 16.8% and was not affected by administration of rIFN-alpha2b. CONCLUSIONS: At the doses and schedule used in this study, the combination of ZDV with rIFN-alpha2b was not therapeutically superior to ZDV alone and was less well tolerated. The addition of rIFN-alpha2b to ZDV did not prevent or delay the development of ZDV resistance.

Keywords: CLINICAL TRIAL CLINICAL TRIAL, PHASE II JOURNAL ARTICLE RANDOMIZED CONTROLLED TRIAL Acquired Immunodeficiency Syndrome/DRUG THERAPY/MORTALITY/ PHYSIOPATHOLOGY/VIROLOGY Adolescence Adult Anti-HIV Agents/ADVERSE EFFECTS/*THERAPEUTIC USE Body Weight *Community Health Services Consumer Product Safety CD4 Lymphocyte Count Drug Therapy, Combination Female Human HIV Infections/*DRUG THERAPY/MORTALITY/PHYSIOPATHOLOGY/VIROLOGY Interferon Alfa-2b/ADVERSE EFFECTS/*THERAPEUTIC USE Male Reverse Transcriptase Inhibitors/ADVERSE EFFECTS/*THERAPEUTIC USE Support, Non-U.S. Gov't Zidovudine/ADVERSE EFFECTS/*THERAPEUTIC USE
990630
A9960978

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