Ribavirin pharmacodynamics in high-risk patients for acquired immunodeficiency syndrome

• Published in: Clinical pharmacology and therapeutics Vol. 42; no. 4; p. 365
• Main Authors: Roberts, R B, Laskin, O L, Laurence, J, Scavuzzo, D, Murray, H W, Kim, Y T, Connor, J D
• Format: Journal Article
• Language: English
• Published: United States 01.10.1987
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - immunology; Administration, Oral; Adult; Clinical Trials as Topic; Double-Blind Method; HIV - drug effects; HIV - isolation & purification; Humans; Interferon-gamma - blood; Leukocyte Count; Lymphocytes - immunology; Male; Middle Aged; Random Allocation; Reverse Transcriptase Inhibitors; Ribavirin - administration & dosage; Ribavirin - adverse effects; Ribavirin - pharmacology; Ribonucleosides - pharmacology; Time Factors; Viral Plaque Assay; Virus Replication - drug effects
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1987.165

Ribavirin was administered orally in escalating doses for 2 or 4 weeks to 15 symptom-free, human immunodeficiency virus seropositive homosexual men with generalized lymphadenopathy. Reverse transcriptase activity was inhibited during therapy when steady-state plasma concentrations were greater than 6 mumol/L. These concentrations were achieved with 1200 or 2400 mg/day for 2 weeks or a loading dose of 2400 mg/day for 3 days followed by 600 mg/day for 4 weeks. Drug accumulation occurred at all doses. The elimination half-life appeared to be approximately 2 weeks. Reversible adverse reactions, principally resulting in central nervous system symptoms and anemia, correlated with dose and duration of therapy. Immunologic enhancement of T-lymphocyte-mediated mitogen-induced responses was observed in the majority of patients who had reduction in reverse transcriptase activity. However, specific T4+ lymphocyte-mediated antigen-induced responses increased to within the normal range in only three patients. Significant enhancement appeared to correlate with the severity of baseline antigen-induced functional impairment. These data indicate that oral ribavirin can be given for at least 1 month with acceptable toxicity at doses that appear to inhibit human immunodeficiency virus replication.