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

15 September 1994 | Volume 121 Issue 6 | Pages 423-429

Objective: To determine the effect of interferon- 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 x 10⁹/L who were refractory to 1 month of full-dose (1000 mg/d) zidovudine.

Intervention: Interferon- (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; ß₂-µglobulin in serum; and platelet-associated IgG.

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

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

Author and Article Information

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-).