Comparative Clinical and Laboratory Evaluation of the Prophylactic Capacity of Ribavirin, Amantadine Hydrochloride, and Placebo in Induced Human Influenza Type A

Abstract

The comparative prophylactic effectiveness of oral treatment with ribavirin (1-β-d-ribofuranosyl-l,2,4,-triazole-3-carboxamide; virazole) and amantadine hydrochloride against artificially induced infection with influenza A virus was evaluated in 29 seronegative men who received ribavirin capsules (200 mg) three times daily, placebo capsules three times daily, or amantadine capsules (100 mg) twice daily. Medication was started two days before the inoculation of 2 x 10⁴ 50% tissue culture infective doses of A/University of Maryland/2/74 (H3N2) influenza virus and was continued for eight days after challenge. Nine of the 10 subjects who received ribavirin, eight of the nine subjects who received placebo, and six of the 10 subjects who received amantadine developed influenzal illness. Significantly less virus was isolated from the amantadine-treated group than from the placebo-treated or the ribavirin-treated group. Antibody responses of the ribavirin-treated and placebo-treated groups were quite similar to each other; however, prophylactic treatment with amantadine significantly reduced titers of serum antibody and febrile responses. In a separate clinical trial involving challenge with A/Dunedin/73 (H3N2) influenza virus, ribavirin also failed to show prophylactic effectiveness.