INTERFERON-ALPHA IS EFFECTIVE IN THE TREATMENT OF HIV-1-RELATED, SEVERE, ZIDOVUDINE-RESISTANT THROMBOCYTOPENIA - A PROSPECTIVE, PLACEBO-CONTROLLED, DOUBLE-BLIND TRIAL

Objective: To determine the effect of interferon-alpha for severe, zid ovudine-resistant, HIV-1-related thrombocytopenia. Design: Prospective , randomized, double-blind, placebo-controlled, multicenter, crossover trial. Setting: Outpatient clinics in Central Northern Italy. Patient s: 15 sequential patients positive for HIV-1 with platelet counts less than 25 x 10(9)/L who were refractory to 1 month of full-dose (1000 m g/d) zidovudine. Intervention: Interferon-alpha (3 million units) or p lacebo (1 mL saline) three times a week subcutaneously for 4 weeks, fo llowed by a 4-week washout period. Patients were then switched to the alternative treatment for the next 4 weeks, followed by another 4 week s of washout, and they were randomly assigned to either sequence of tr eatment. Patients received zidovudine (200 mg three times daily) throu ghout the study. Measurements: The primary end point was the platelet count (measured weekly). Secondary end points were qualitative assessm ent of the platelet response; bleeding time; p24 antigen in serum; CD4 /CD8 counts; beta(2)-microglobulin in serum; and platelet-associated I gG. Results: Interferon-alpha significantly increased platelet counts in the 12 patients who completed the study (baseline level, 15.6 +/- 7 .1 x 10(9)/L; after 4 weeks of interferon-alpha therapy, 82.2 +/- 52.2 x 10(9)/L). The estimated increase in the platelet count after interf eron-alpha compared with placebo was 60.0 x 10(9)/L (95% CI, 23.2 to 9 6.8 x 10(9)/L). The increase was already statistically significant aft er 3 weeks (66.6 +/- 49.7 x 10(9)/L) and remained significantly increa sed 1 week after discontinuing interferon-alpha therapy (58.2 +/- 45.0 x 10(9)/L). Placebo did not modify the platelet count. The bleeding t ime was significantly shortened by interferon-alpha. Four of 12 patien ts who had more serious alterations of some measures reflecting diseas e severity did not respond to interferon-alpha. No relevant side effec ts were observed. Conclusions: Interferon-alpha is a safe and effectiv e treatment for zidovudine-resistant, HIV-related thrombocytopenia.