High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication.
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.
de Jong
M D
MD
National AIDS Therapy Evaluation Centre, Department of Infectious Diseases, University of Amsterdam, Netherlands.
Vella
S
S
Carr
A
A
Boucher
C A
CA
Imrie
A
A
French
M
M
Hoy
J
J
Sorice
S
S
Pauluzzi
S
S
Chiodo
F
F
Weverling
G J
GJ
van der Ende
M E
ME
Frissen
P J
PJ
Weigel
H M
HM
Kauffmann
R H
RH
Lange
J M
JM
Yoon
R
R
Moroni
M
M
Hoenderdos
E
E
Leitz
G
G
Cooper
D A
DA
Hall
D
D
Reiss
P
P
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*
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D011725:Pyridines; D012367:RNA, Viral; D019829:Nevirapine