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Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique

BACKGROUND: In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations...

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Autores principales: Lamorde, Mohammed, Fillekes, Quirine, Sigaloff, Kim, Kityo, Cissy, Buzibye, Allan, Kayiwa, Joshua, Merry, Concepta, Nakatudde-Katumba, Lillian, Burger, David, de Wit, Tobias F Rinke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158037/
https://www.ncbi.nlm.nih.gov/pubmed/25176164
http://dx.doi.org/10.1186/1471-2334-14-473
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author Lamorde, Mohammed
Fillekes, Quirine
Sigaloff, Kim
Kityo, Cissy
Buzibye, Allan
Kayiwa, Joshua
Merry, Concepta
Nakatudde-Katumba, Lillian
Burger, David
de Wit, Tobias F Rinke
author_facet Lamorde, Mohammed
Fillekes, Quirine
Sigaloff, Kim
Kityo, Cissy
Buzibye, Allan
Kayiwa, Joshua
Merry, Concepta
Nakatudde-Katumba, Lillian
Burger, David
de Wit, Tobias F Rinke
author_sort Lamorde, Mohammed
collection PubMed
description BACKGROUND: In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to HIV treatment outcomes in Ugandan patients. METHODS: Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC method. Plasma nevirapine concentrations <3.0 mg/L using HPLC were considered subtherapeutic. Negative/positive predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined. Virologic testing and, if applicable, HIV drug resistance testing was performed. RESULTS: Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17 (4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A cut-off value of 1.60 mg/L nevirapine in saliva was associated with a negative/positive predictive value of 0.99/0.72 and a sensitivity/specificity of 87%/98% for predicting subtherapeutic nevirapine plasma concentrations, respectively. Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral load results > 400 copies/mL. Patients with nevirapine concentrations in plasma <3.0 mg/L had an Odds Ratio of 3.29 (95% CI: 1.00 – 10.74) for virological failure (viral load >400 copies/mL). CONCLUSIONS: The low-cost TLC technique for monitoring nevirapine in saliva was unsuccessful but monitoring nevirapine saliva and plasma concentrations using HPLC was shown to be feasible in the research/specialist context in Uganda. Further optimization and validation is required for the low-cost TLC technique.
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spelling pubmed-41580372014-09-10 Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique Lamorde, Mohammed Fillekes, Quirine Sigaloff, Kim Kityo, Cissy Buzibye, Allan Kayiwa, Joshua Merry, Concepta Nakatudde-Katumba, Lillian Burger, David de Wit, Tobias F Rinke BMC Infect Dis Research Article BACKGROUND: In resource limited settings access to laboratory monitoring of HIV treatment is limited and therapeutic drug monitoring is generally unavailable. This study aimed to evaluate nevirapine concentrations in saliva using low-cost thin-layer chromatography (TLC) and nevirapine concentrations in plasma and saliva using high performance liquid chromatography (HPLC) methods; and to correlate nevirapine plasma concentrations to HIV treatment outcomes in Ugandan patients. METHODS: Paired plasma and stimulated saliva samples were obtained from Ugandan, HIV-infected adults on nevirapine-based ART. Nevirapine concentrations were measured using a validated HPLC method and a novel TLC method. Plasma nevirapine concentrations <3.0 mg/L using HPLC were considered subtherapeutic. Negative/positive predictive values of different thresholds for subtherapeutic nevirapine concentrations in saliva were determined. Virologic testing and, if applicable, HIV drug resistance testing was performed. RESULTS: Median (interquartile range, IQR) age of 297 patients was 39.1 (32.8-45.2) years. Three hundred saliva and 287 plasma samples were available for analysis. Attempts failed to determine nevirapine saliva concentrations by TLC. Using HPLC, median (IQR) nevirapine concentrations in saliva and plasma were 3.40 (2.59-4.47) mg/L and 6.17 (4.79-7.96) mg/L, respectively. The mean (coefficient of variation,%) nevirapine saliva/plasma ratio was 0.58 (62%). A cut-off value of 1.60 mg/L nevirapine in saliva was associated with a negative/positive predictive value of 0.99/0.72 and a sensitivity/specificity of 87%/98% for predicting subtherapeutic nevirapine plasma concentrations, respectively. Only 5% (15/287) of patients had subtherapeutic nevirapine plasma concentrations, of which 3 patients had viral load results > 400 copies/mL. Patients with nevirapine concentrations in plasma <3.0 mg/L had an Odds Ratio of 3.29 (95% CI: 1.00 – 10.74) for virological failure (viral load >400 copies/mL). CONCLUSIONS: The low-cost TLC technique for monitoring nevirapine in saliva was unsuccessful but monitoring nevirapine saliva and plasma concentrations using HPLC was shown to be feasible in the research/specialist context in Uganda. Further optimization and validation is required for the low-cost TLC technique. BioMed Central 2014-09-01 /pmc/articles/PMC4158037/ /pubmed/25176164 http://dx.doi.org/10.1186/1471-2334-14-473 Text en © Lamorde et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lamorde, Mohammed
Fillekes, Quirine
Sigaloff, Kim
Kityo, Cissy
Buzibye, Allan
Kayiwa, Joshua
Merry, Concepta
Nakatudde-Katumba, Lillian
Burger, David
de Wit, Tobias F Rinke
Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
title Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
title_full Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
title_fullStr Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
title_full_unstemmed Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
title_short Therapeutic drug monitoring of nevirapine in saliva in Uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
title_sort therapeutic drug monitoring of nevirapine in saliva in uganda using high performance liquid chromatography and a low cost thin-layer chromatography technique
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158037/
https://www.ncbi.nlm.nih.gov/pubmed/25176164
http://dx.doi.org/10.1186/1471-2334-14-473
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