Therapeutic Drug Monitoring of Nevirapine in Resource‐Limited Settings

L'homme, Rafaëlla F. A.; Muro, Eva; Droste, Jacqueline A. H.; Wolters, Liselotte; Kolmer, Noor W. J. van Ewijk-Beneken; Schimana, Werner; Burger, David M.

doi:10.1086/592694

Cited by 15 publications

(20 citation statements)

References 11 publications

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“…Nevirapine concentrations were measured in paired plasma and saliva samples using a validated HPLC method at the Infectious Diseases Institute, Kampala, Uganda (lower limit of quantification 0.05 mg/L) [18]. The accuracy of the HPLC assay ranged from 94 – 96% for saliva and 94 – 99% for plasma.…”

Section: Methodsmentioning

confidence: 99%

“…Nevirapine concentrations in saliva samples were also measured at the JCRC reference laboratory in Kampala, Uganda using an earlier described TLC technique which reported a sensitivity of 92% and specificity of 99% when compared to plasma concentrations determined by HPLC [18]. For HPLC measurements, we determined the negative and positive predictive values of different thresholds for sub-therapeutic saliva concentrations of nevirapine for predicting nevirapine plasma concentrations above or below 3.0 mg/L.…”

Section: Methodsmentioning

confidence: 99%

“…To this end, one African study validated the use of a TLC technique as a low cost alternative to HPLC for TDM in patients using nevirapine [18]. Nevirapine concentrations are generally measured in blood samples, but saliva has been reported to be an acceptable alternative matrix [19, 20].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2014

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BackgroundIn 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.MethodsPaired 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.ResultsMedian (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).ConclusionsThe 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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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

et al. 2014

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“…In contrast, thin-layer chromatography (TLC) is a simple and inexpensive analytical tool that has been used for the detection of NVP concentrations in fixed-dose combination tablets, human plasma, saliva, and umbilical cord blood. [17][18][19][20] We report on the development of a low-cost method to analyze NVP in human hair samples using TLC.Nevirapine hemihydrate, nevirapine-D5, atazanavir, efavirenz, emtricitabine, lamivudine, raltegravir, ritonavir, stavudine, tenofovir, and zidovudine, along with organic solvents, were obtained from relevant commercial laboratories. Drug-free blank human hair samples were obtained from six HIV-noninfected volunteers.…”

mentioning

confidence: 99%

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confidence: 99%

Short Communication: A Low-Cost Method for Analyzing Nevirapine Levels in Hair as a Marker of Adherence in Resource-Limited Settings

Gandhi

Yang

Bacchetti

et al. 2014

AIDS Research and Human Retroviruses

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The measurement of antiretroviral concentrations in hair is emerging as an important technology to objectively quantify adherence to combination antiretroviral therapy. Hair levels of antiretrovirals are the strongest independent predictor of virologic success in large prospective cohorts of HIV-infected patients and surpass self-report in predicting outcomes. Hair is easy to collect and store, but validated methods to analyze antiretroviral levels in hair using liquid chromatography tandem mass spectrometry (LC-MS/MS) are expensive. We report here on the development of a thin-layer chromatography (TLC) assay for the semiquantitative analysis of nevirapine in hair. TLC assay results from 11 samples were consistent with results using LC-MS/MS [Spearman correlation coefficient 0.99 (95% CI 0.95-0.996)]. This simple, low-cost method of analyzing nevirapine concentrations in hair may provide a novel monitoring tool for antiretroviral adherence in resource-limited settings and merits further study in clinical settings.A dherence to antiretroviral (ARV) therapy is essential for the realization of virologic, immunologic, and clinical benefits, but the limitations of self-report and other commonly used adherence measures are well-described.1 The measurement of ARV concentrations in hair as a biological measure of adherence is emerging as an important technology to objectively quantify adherence to combination antiretroviral therapy (cART).2 Hair levels of ARVs are the strongest independent predictor of virologic success in large prospective cohorts of HIV-infected patients, 3-6 and surpass self-report in predicting outcomes.3 Moreover, hair levels can serve as a measure of exposure to maternal ARVs in infants during pregnancy and breastfeeding. Since drugs accumulate in hair over prolonged periods, 8, 8a a single measurement of an ARV in a hair sample provides a longer-term measure of adherence than a single plasma level, which captures only short-term use.9-13 Nevirapine (NVP) is widely prescribed in cART regimens for the treatment of HIVinfected adults and children in global settings, 14 and plays a role in worldwide perinatal transmission prevention. A lowcost testing method for analyzing NVP levels in small hair samples that could be performed in local laboratories would therefore be useful for monitoring adherence to NVP-based regimens in resource-limited settings.Hair samples are simple and inexpensive to collect and can be stored at room temperature prior to analysis. Unlike phlebotomy, hair collection is noninvasive and does not require specific skills or sterile equipment. These features provide obvious cost and feasibility advantages for hair collection and storage, over plasma but validated methods of analyzing ARV levels in hair samples use liquid chromatography/tandem mass spectrometry (LC-MS/MS). 15,16 The LC-MS/MS method for analyzing NVP in hair samples is highly sensitive, 16 but the equipment required is expensive, limiting its suitability in resource-limited settings. In contrast, thin-laye...

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Application of Planar Chromatography in Pharmaceutical, Clinical, and Toxicological Analysis

Waligóra

Tyrpień-Golder

2022

Handbook of Bioanalytics

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Therapeutic Drug Monitoring of Nevirapine in Resource‐Limited Settings

Cited by 15 publications

References 11 publications

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

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

Short Communication: A Low-Cost Method for Analyzing Nevirapine Levels in Hair as a Marker of Adherence in Resource-Limited Settings

Application of Planar Chromatography in Pharmaceutical, Clinical, and Toxicological Analysis

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