Interferon-Alpha Is Effective in the Treatment of HIV-1–Related, Severe, Zidovudine-Resistant Thrombocytopenia: A Prospective, Placebo-controlled, Double-Blind Trial

  1. Massimo Marroni, MD;
  2. Paolo Gresele, MD, PhD;
  3. Giuseppe Landonio, MD;
  4. Adriano Lazzarin, MD;
  5. Massimo Coen, MD;
  6. Roberta Vezza, PharmD;
  7. Marina Silva Sinnone, MD;
  8. Enrico Boschetti, MD;
  9. Anna Maria Nosari, MD;
  10. Giuliano Stagni, MD;
  11. Giuseppe Giorgio Nenci, MD; and
  12. Sergio Pauluzzi, MD
  1. From the University of Perugia, Perugia; Niguarda Hospital, Milan; San Raffaele University Hospital, Milan; Sacco Hospital, Milan, Italy. Requests for Reprints: Paolo Gresele, MD, PhD, Institute of Internal and Vascular Medicine, University of Perugia, via E. dal Pozzo, I-06126 Perugia, Italy. Acknowledgments: The authors thank Ms. Catia Alessandri for secretarial assistance; the following nurses for their assistance with drug treatment: Ms. Salvatrice Ferrini, Mr. Ennio Giommetti, Ms. Rossella Giorgetti, Ms. Manuela Simioni, Ms. Isa Strazio, and Ms. Francesca Visconti; and Daniela Cattaneo, MD, and Giuseppe V.L. De Socio, MD, who helped with patient management. Grant Support: Wellcome, Italia, provided the study drug (interferon-α).

    Abstract

    Objective: To determine the effect of interferon-α for severe, zidovudine-resistant, HIV-1–related thrombocytopenia.

    Design: Prospective, randomized, double-blind, placebo-controlled, multicenter, crossover trial.

    Setting: Outpatient clinics in Central Northern Italy.

    Patients: 15 sequential patients positive for HIV-1 with platelet counts less than 25 × 109/L who were refractory to 1 month of full-dose (1000 mg/d) zidovudine.

    Intervention: Interferon-α (3 million units) or placebo (1 mL saline) three times a week subcutaneously for 4 weeks, followed by a 4-week washout period. Patients were then switched to the alternative treatment for the next 4 weeks, followed by another 4 weeks of washout, and they were randomly assigned to either sequence of treatment. Patients received zidovudine (200 mg three times daily) throughout the study.

    Measurements: The primary end point was the platelet count (measured weekly). Secondary end points were qualitative assessment of the platelet response; bleeding time; p24 antigen in serum; CD4/CD8 counts; β2-microglobulin in serum; and platelet-associated IgG.

    Results: Interferon-α significantly increased platelet counts in the 12 patients who completed the study (baseline level, 15.6 ± 7.1 × 109/L; after 4 weeks of interferon-α therapy, 82.2 ± 52.2 × 109/L). The estimated increase in the platelet count after interferon-α compared with placebo was 60.0 × 109/L (95% CI, 23.2 to 96.8 × 109/L). The increase was already statistically significant after 3 weeks (66.6 ± 49.7 × 109/L) and remained significantly increased 1 week after discontinuing interferon-α therapy (58.2 ± 45.0 × 109/L). Placebo did not modify the platelet count. The bleeding time was significantly shortened by interferon-α. Four of 12 patients who had more serious alterations of some measures reflecting disease severity did not respond to interferon-α. No relevant side effects were observed.

    Conclusions: Interferon-α is a safe and effective treatment for zidovudine-resistant, HIV-related thrombocytopenia.

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    1. Ann Intern Med September 15, 1994 vol. 121 no. 6 423-429
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