PMID- 10077172 OWN - NLM STAT- MEDLINE DCOM- 19990401 LR - 20191024 IS - 1077-9450 (Print) IS - 1077-9450 (Linking) VI - 20 IP - 3 DP - 1999 Mar 1 TI - 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. PG - 245-54 AB - 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. FAU - Krown, S E AU - Krown SE AD - Department of Medicine, Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, New York, New York 10021, USA. FAU - Aeppli, D AU - Aeppli D FAU - Balfour, H H Jr AU - Balfour HH Jr LA - eng PT - Clinical Trial PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Acquir Immune Defic Syndr Hum Retrovirol JT - Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association JID - 9501482 RN - 0 (Anti-HIV Agents) RN - 0 (Interferon alpha-2) RN - 0 (Interferon-alpha) RN - 0 (Recombinant Proteins) RN - 0 (Reverse Transcriptase Inhibitors) RN - 4B9XT59T7S (Zidovudine) SB - IM MH - Acquired Immunodeficiency Syndrome/drug therapy/mortality/physiopathology/virology MH - Adolescent MH - Adult MH - Anti-HIV Agents/adverse effects/*therapeutic use MH - Body Weight MH - CD4 Lymphocyte Count MH - *Community Health Services MH - Consumer Product Safety MH - Drug Therapy, Combination MH - Female MH - HIV Infections/*drug therapy/mortality/physiopathology/virology MH - Humans MH - Interferon alpha-2 MH - Interferon-alpha/adverse effects/*therapeutic use MH - Male MH - Recombinant Proteins MH - Reverse Transcriptase Inhibitors/adverse effects/*therapeutic use MH - Zidovudine/adverse effects/*therapeutic use EDAT- 1999/03/17 03:04 MHDA- 2001/03/28 10:01 CRDT- 1999/03/17 03:04 PHST- 1999/03/17 03:04 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1999/03/17 03:04 [entrez] AID - 10.1097/00042560-199903010-00005 [doi] PST - ppublish SO - J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Mar 1;20(3):245-54. doi: 10.1097/00042560-199903010-00005.