RESUMO
OBJECTIVE: To determine the pharmacokinetics of cessation of nevirapine (NVP) in order to design clinical protocols which will reduce the risk of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs). METHODS: In a case study, NNRTI genotypic resistance was demonstrated in a patient discontinuing therapy for toxicity. Subsequently, nine patients receiving NVP-containing antiretroviral regimens and stopping treatment were recruited. Patients were advised to continue the nucleoside analogue reverse transcriptase inhibitor (NRTI) backbone for 5 days following cessation of NVP. Plasma NVP concentrations were determined over 7-10 days after the last dose. HIV-1 reverse transcriptase genotyping was performed at viral load rebound (approximately day 21 following cessation) to detect mutations associated with reduced NNRTI sensitivity. RESULTS: The median predicted time for plasma NVP concentration to fall below the inhibitory concentration (IC)(50) of wild-type virus was 168 h (range 108-264 h). De novo genotypic mutations conferring resistance to NRTIs or NNRTIs were not demonstrated following cessation of therapy. CONCLUSIONS: The prolonged elimination half-life of NVP compared with NRTIs, which persists even after 20 weeks of therapy, raises concern over the development of NNRTI resistance if all three drugs are stopped together. Continuation of the NRTI backbone for a further 5 days, allowing the elimination of NVP, may avoid the development of drug resistance.
Assuntos
Fármacos Anti-HIV/farmacocinética , Infecções por HIV/tratamento farmacológico , Nevirapina/farmacocinética , Inibidores da Transcriptase Reversa/farmacocinética , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Farmacorresistência Viral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/efeitos adversos , Carga ViralRESUMO
Mislabeled umbilical cord blood specimens were identified as an important and difficult problem to solve. Quality improvement principles were employed after education-based interventions failed to achieve measurable improvement. A small interdisciplinary working group of key stakeholders investigated, designed, and evaluated interventions for a solution. This article describes a system-based change where substantial qualitative and quantitative improvements were measured. The success of the change is attributed to the involvement and commitment by key stakeholders and use of systems reengineering principles.
