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.