High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication

M. D. De Jong, S. Vella, A. Carr, C. A.B. Boucher, A. Imrie, M. French, J. Hoy, S. Sorice, S. Pauluzzi, F. Chiodo, G. J. Weverling, M. E. Van Der Ende, Ph J. Frissen, H. M. Weigel, R. H. Kauffmann, J. M.A. Lange, R. Yoon, M. Moroni, E. Hoenderdos, G. LeitzD. A. Cooper, D. Hall, P. Reiss

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Abstract

High-dose nevirapine treatment has been reported to confer sustained antiretroviral effects, despite a rapid development of resistance. The use of this strategy was evaluated in 20 previously untreated human immunodeficiency virus type 1 (HIV-1) p24 antigenemic persons with CD4 cell counts between 100 and 500/mm3. Treatment consisted of 400 mg of nevirapine, after a 2-week lead-in dose of 200 mg. Rash was the most frequently reported adverse event, occurring in 25%. While sustained declines in p24 antigen levels were observed in the majority, serum HIV-1 RNA load and CD4 cell counts returned to baseline values within 12 weeks in virtually all subjects. The resistance-conferring tyrosine-to-cysteine substitution at reverse transcriptase position 181 was detected after 4 weeks in most subjects. These observations suggest that plasma drug levels attained with high-dose nevirapine were not sufficient to inhibit nevirapine-resistant virus, although they were ~2-fold higher than reported IC50 values of resistant virus.

Original languageEnglish
Pages (from-to)966-970
Number of pages5
JournalJournal of Infectious Diseases
Volume175
Issue number4
DOIs
Publication statusPublished - 1 Jan 1997

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