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 Boucher, A. Imrie, M French, J Hoy, S Sorice, S. Pauluzzi, G.J. Weverling, M E van der Ende, P J Frissen, H M Weigel, R H Kauffmann, J M Lange, R Yoon, M Moroni, E Hoenderdos, G Leitz, D A CooperD 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 approximately 2-fold higher than reported IC50 values of resistant virus.

Original languageEnglish
Pages (from-to)966-70
Number of pages5
JournalThe Journal of infectious diseases
Volume175
Issue number4
Publication statusPublished - Apr 1997

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