TY - JOUR
T1 - High-dose nevirapine
T2 - Safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection
AU - Havlir, Diane
AU - Cheeseman, Sarah H.
AU - Mc Laughlin, Margaret
AU - Murphy, Robert
AU - Erice, Alejo
AU - Spector, Stephen A.
AU - Greenough, Thomas C.
AU - Sullivan, John L.
AU - Hall, David
AU - Myers, Maureen
AU - Lamson, Michael
AU - Richman, Douglas D.
N1 - Funding Information:
Received 16 February 1994: revised 15 July 1994. Presented in part: IX International Conference on AIDS. Berlin. (OJune 1993 (slide presentation WS B26 I: abstract Po B26 2109). Approval of the protocol and informed consent documents were obtained from institutional review boards at participating sites. All patients signed an informed consent statement before enrollment. Financial support: National Institutes of Health (AI-27670. -29164. and -25831): Boehringer-lngelheirn: Research Center for AIDS and HIV Infection. San Diego VA Medical Center: and University of Massachusetts, Worcester. Reprints or correspondence: Dr. Diane Havlir. UCSD Treatment Center. 2760 Fifth Ave.. Suite 300. San Diego. CA 92103.
PY - 1995/3
Y1 - 1995/3
N2 - Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at ≤200 mg/day due to the selection of resistant virus. To examine if higher levels of nevirapine could produce sustained antiviral activity, its safety, pharmacokinetics, and antiviral activity at 400 mg/day were studied in 21 patients. There was a rapid reduction in immune complex-dissociated p24 antigen and serum human immunodeficiency virus RNA concentration in all patients, and 8 of 10 patients had > 50% reduction at 8 weeks. Nevirapine-resistant virus was isolated from all subjects tested at 12 weeks: The mean plasma trough level (4.0 µg/mL [l5.8µg/M]) exceeded the mean IC50of resistant virus. Rash developed in 48% of patients and was a dose-limiting toxicity factor in 6. These data suggest that clinical testing of potent antiviral compounds that select for drug-resistant virus is justified to determine if serum levels of drug sufficient to overcome resistant virus can be attained.
AB - Nevirapine, a potent nonnucleoside reverse transcriptase inhibitor, produces a transient antiviral effect at ≤200 mg/day due to the selection of resistant virus. To examine if higher levels of nevirapine could produce sustained antiviral activity, its safety, pharmacokinetics, and antiviral activity at 400 mg/day were studied in 21 patients. There was a rapid reduction in immune complex-dissociated p24 antigen and serum human immunodeficiency virus RNA concentration in all patients, and 8 of 10 patients had > 50% reduction at 8 weeks. Nevirapine-resistant virus was isolated from all subjects tested at 12 weeks: The mean plasma trough level (4.0 µg/mL [l5.8µg/M]) exceeded the mean IC50of resistant virus. Rash developed in 48% of patients and was a dose-limiting toxicity factor in 6. These data suggest that clinical testing of potent antiviral compounds that select for drug-resistant virus is justified to determine if serum levels of drug sufficient to overcome resistant virus can be attained.
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U2 - 10.1093/infdis/171.3.537
DO - 10.1093/infdis/171.3.537
M3 - Article
C2 - 7533197
AN - SCOPUS:0028930117
SN - 0022-1899
VL - 171
SP - 537
EP - 545
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -
