Study Objective: To assess safety, tolerance, and the clinical and laboratory effects of oral ribavirin in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex.
Design: Three uncontrolled phase I trials of increasing duration: 14 days, 8 weeks, and 12 months.
Setting: Outpatient clinic of a university-referral hospital.
Patients: All patients were antibody-positive for the human immunodeficiency virus (HIV) by radioimmunoprecipitation assay, all had recovered from Pneumocystis carinii pneumonia, and none had Kaposi sarcoma at entry. Nine of ten patients with AIDS had less than 100 CD4+ lymphocytes/mm3 at entry and all patients with the AIDS-related complex had fewer than 200 CD4+ lymphocytes/mm3. Five patients with AIDS and five with the AIDS-related complex entered the 14-day trial. All but two patients with AIDS went on to the 8-week trial, along with seven additional patients with AIDS. Five surviving patients with AIDS and 3 patients with the AIDS-related complex went on to the 1-year study.
Interventions: Oral ribavirin, 1200 mg twice daily for 3 days was given, followed by 300 mg twice daily for 11 days. During an 8-week trial, a loading dose of oral ribavirin was administered for 3 days, followed by a dose of 300 mg twice daily for 8 weeks. Prolonged regimen of a 3-day loading dose was given, followed by a dose of 300 mg twice daily for 1 year.
Measurements and Main Results: Ribavirin treatment was well tolerated, with anemia requiring transfusion in one of the ten patients with AIDS receiving the drug for 8 weeks; no other significant toxicity occurred. Six of nine patients initially positive for HIV-1 in blood became negative during ribavirin treatment. Six of nine patients with AIDS had a twofold improvement in lymphoproliferative response to at least one lectin with ribavirin treatment. Mean survival from first episode of P. carinii pneumonia was 17.3 months in patients with AIDS receiving 8 weeks of ribavirin and 21.2 months in patients with AIDS receiving prolonged treatment.
Conclusions: Oral ribavirin, 600 mg daily, was well tolerated and safe in the patients with severe AIDS and the AIDS-related complex. Ribavirin therapy merits extensive evaluation in a multicenter controlled trial to assess its efficacy.