Ribavirin pharmacodynamics in high-risk patients for acquired immunodeficiency syndrome.
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.
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D000284:Administration, Oral; D000328:Adult; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006678:HIV / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007958:Leukocyte Count; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D018894:Reverse Transcriptase Inhibitors; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012263:Ribonucleosides / Q000494:pharmacology*; D013997:Time Factors; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D018894:Reverse Transcriptase Inhibitors; D012263:Ribonucleosides; D012254:Ribavirin; D007371:Interferon-gamma