Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-α(2a) in patients with HIV: AIDS Clinicals Trials Group Study 197

Margaret A Fischl, D. D. Richman, M. Saag, Chiang Meng Tze Chiang Meng, K. E. Squires, J. Holden- Wiltse, P. M. Meehan

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Abstract

We conducted a three-arm, randomized, phase II study to evaluate the combination of zidovudine (600 mg/day) and zalcitabine (2.25 mg/day) alone or with one of two interferon-α(2a) doses (1 mIU or 6 mIU daily). Primary study endpoints included toxicity and changes from baseline for plasma HIV-1 RNA, CD4 cells, and quantitative microculture at weeks 8 and 24. Sixty-three patients with HIV infection and <400 CD4 cells/mm3 were enrolled; four patients discontinued therapy within 2 weeks. Adverse event rates were 37%, 32%, and 60%, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups. Increasing doses of interferon resulted in significantly greater hematologic toxicity (p = 0.03) and peripheral neuropathy (p = 0.02). Plasma HIV-1 RNA reductions were noted across all treatment groups at week 8 (p < 0.001) but only for the nucleoside and 1-mIU interferon combination groups at week 24 (p < 0.001). Mean reductions in HIV- 1 RNA at week 8 were 0.94, 1.29, and 1.40 log10, respectively, for the nucleoside, 1-mIU interferon, and 6-mIU interferon combination groups (p = 0.05); no differences were noted at week 24. No differences in CD4 cell counts were seen. The addition of interferon-α(2a) to zidovudine and zalcitabine resulted in transient enhanced decreases in viral load and increased toxicity.

Original languageEnglish
Pages (from-to)247-253
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume16
Issue number4
StatePublished - Dec 22 1997

Fingerprint

Zalcitabine
Zidovudine
Interferons
Antiviral Agents
Acquired Immunodeficiency Syndrome
Clinical Trials
HIV
Safety
Nucleosides
HIV-1
RNA
Therapeutics
Peripheral Nervous System Diseases
CD4 Lymphocyte Count
Viral Load
HIV Infections

Keywords

  • Combination therapy
  • HIV infection
  • Interferon

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Cite this

Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-α(2a) in patients with HIV : AIDS Clinicals Trials Group Study 197. / Fischl, Margaret A; Richman, D. D.; Saag, M.; Tze Chiang Meng, Chiang Meng; Squires, K. E.; Holden- Wiltse, J.; Meehan, P. M.

In: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 16, No. 4, 22.12.1997, p. 247-253.

Research output: Contribution to journalArticle

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