Therapeutic drug monitoring of nevirapine in resource-limited settings
Clinical Infectious Diseases
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; Nijmegen University Centre for Infectious Diseases, Nijmegen, Netherlands; Kilimanjaro Christian Medical Centre, Moshi, Tanzania; Dept. of Clinical Pharmacy, 864 Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, Netherlands
Background. We developed a simple and inexpensive thin-layer chromatography (TLC) assay for semiquantitative detection of saliva concentrations of nevirapine in resource-limited settings. The method was validated in an African target population. Methods. Paired plasma and saliva nevirapine concentrations were assayed by high-performance liquid chromatography (HPLC); saliva concentrations of nevirapine were also assayed by TLC. The rate of false-positive results was the proportion of subtherapeutic nevirapine saliva and plasma concentrations determined by HPLC that were judged to be therapeutic in saliva specimens by TLC. The rate of false-negative results was the proportion of therapeutic nevirapine saliva and plasma concentrations determined by HPLC that were judged to be subtherapeutic in saliva specimens by TLC. The extent of agreement in TLC readings between 5 technicians and 2 batches of TLC sheets was evaluated. Results. Twenty-five (9%) of 286 African adults had a subtherapeutic plasma nevirapine concentration. The median ratio of nevirapine concentrations in saliva to those in plasma was 0.51:1. The rate of false-positive results for TLC was 0% (0 of 23 specimens) when TLC results were compared with HPLC results for saliva specimens and 8% (2 of 25 specimens) when TLC results were compared with HPLC results for plasma specimens. The rate of false-negative results for TLC was 1% (3 of 263 specimens) when TLC results were compared with HPLC results for saliva specimens and 1% (3 of 261 specimens) when TLC results were compared with HPLC results for plasma specimens. The extent of agreement of TLC results was substantial for the 5 technicians (Fleiss's κ = 0.77) and for the 2 batches of sheets (Cohen's p0.80). Conclusions. The TLC assay was found to be sensitive, specific, and robust in the detection of subtherapeutic nevirapine concentrations in saliva specimens obtained from African HIV-infected adults. It is an attractive alternative to HPLC for therapeutic drug monitoring of nevirapine in resource-limited settings. © 2008 by the Infectious Diseases Society of America. All rights reserved.
lamivudine; nevirapine; stavudine; zidovudine; adolescent; adult; aged; article; controlled study; drug blood level; drug monitoring; drug saliva level; high performance liquid chromatography; human; Human immunodeficiency virus infection; intermethod comparison; major clinical study; priority journal; thin layer chromatography; Adolescent; Adult; Africa; Aged; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Drug Monitoring; False Negative Reactions; False Positive Reactions; Female; HIV Infections; Humans; Male; Middle Aged; Nevirapine; Plasma; Saliva; Sensitivity and Specificity