INTERFERON-ALPHA IN PATIENTS WITH ASYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION - A RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Study objective: To evaluate the toxicity and clinical efficacy of interferon-α2b (IFN-α) in patients with asymptomatic human immunodeficiency virus (HIV) infection. Design: Randomized, placebo-controlled, and double-blind study. Setting: Outpatient clinic of a government referral-based research hospital. Patients: Volunteer sample of 34 patients with asymptomatic HIV infection who had CD4 counts of 400 cells/mm3 or more, positive peripheral blood mononuclear cell cultures for HIV, or p24 antigenemia. Interventions: Patients were randomly assigned to receive either IFN-α or placebo, 35 x 106 units per day subcutaneously. Doses of IFN-α or placebo were modified accordings to predefined laboratory and clinical criteria. Therapy lasted at least 12 weeks. Measurements and main results: Seventeen patients were randomly assigned to each group. The two groups had similar mean CD4 counts at study entry. Thirty-five percent of patients assigned to receive IFN-α withdrew from the study because of toxicity. The average daily dose of IFN-α was 17.5 x 106 units. All patients receiving IFN-α reported flu-like symptoms; other toxicities included granulocytopenia (55%) and elevated liver enzyme levels (45%). While receiving IFN-α, 7 patients (41%) became HIV culture negative (three or more consecutive negative peripheral blood mononuclear cells cultures taken at least 2 weeks apart). In contrast, 2 patients in the placebo group (13%) became culture negative while on study (P = 0.05). During the treatment period, CD4 lymphocyte percentages were sustained at or above the baseline level in patients receiving IFN-α and declined slightly in patients receiving placebo. Of the 32 study patients followed after study (range, 5 to 33 months), no patients in the IFN-α group developed an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection, compared with 5 patients in the placebo group (P = 0.02). Conclusions: Treatment of early-stage HIV infection with IFN-α can result in a decrease in frequency of viral isolation. Although its use may be accompanied by dose-dependent toxicities, IFN-α may have a role in slowing progression of HIV disease.