title: High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication.
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.
authors.affiliation: National AIDS Therapy Evaluation Centre, Department of Infectious Diseases, University of Amsterdam, Netherlands.
authors.forename: M D
authors.initials: MD
authors.lastname: de Jong
authors.forename: S
authors.initials: S
authors.lastname: Vella
authors.forename: A
authors.initials: A
authors.lastname: Carr
authors.forename: C A
authors.initials: CA
authors.lastname: Boucher
authors.forename: A
authors.initials: A
authors.lastname: Imrie
authors.forename: M
authors.initials: M
authors.lastname: French
authors.forename: J
authors.initials: J
authors.lastname: Hoy
authors.forename: S
authors.initials: S
authors.lastname: Sorice
authors.forename: S
authors.initials: S
authors.lastname: Pauluzzi
authors.forename: F
authors.initials: F
authors.lastname: Chiodo
authors.forename: G J
authors.initials: GJ
authors.lastname: Weverling
authors.forename: M E
authors.initials: ME
authors.lastname: van der Ende
authors.forename: P J
authors.initials: PJ
authors.lastname: Frissen
authors.forename: H M
authors.initials: HM
authors.lastname: Weigel
authors.forename: R H
authors.initials: RH
authors.lastname: Kauffmann
authors.forename: J M
authors.initials: JM
authors.lastname: Lange
authors.forename: R
authors.initials: R
authors.lastname: Yoon
authors.forename: M
authors.initials: M
authors.lastname: Moroni
authors.forename: E
authors.initials: E
authors.lastname: Hoenderdos
authors.forename: G
authors.initials: G
authors.lastname: Leitz
authors.forename: D A
authors.initials: DA
authors.lastname: Cooper
authors.forename: D
authors.initials: D
authors.lastname: Hall
authors.forename: P
authors.initials: P
authors.lastname: Reiss
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D019829:Nevirapine; D011725:Pyridines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D011725:Pyridines; D012367:RNA, Viral; D019829:Nevirapine