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Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure
Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therap...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325546/ https://www.ncbi.nlm.nih.gov/pubmed/28235021 http://dx.doi.org/10.1371/journal.pone.0172960 |
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author | Kimulwo, Maureen J. Okendo, Javan Aman, Rashid A. Ogutu, Bernhards R. Kokwaro, Gilbert O. Ochieng, Dorothy J. Muigai, Anne W. T. Oloo, Florence A. Ochieng, Washingtone |
author_facet | Kimulwo, Maureen J. Okendo, Javan Aman, Rashid A. Ogutu, Bernhards R. Kokwaro, Gilbert O. Ochieng, Dorothy J. Muigai, Anne W. T. Oloo, Florence A. Ochieng, Washingtone |
author_sort | Kimulwo, Maureen J. |
collection | PubMed |
description | Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12–156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p = 0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p = 0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3μg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3μg/ml for optimal therapeutic nevirapine level, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p = 0.05) and virologic VF (p = 0.002) in a chi-square test. These mean cNVP levels differed significantly in non-parametric tests between adherence categories at 1hr (p = 0.005) and 4hrs (p = 0.01) and between ART regimen categories at 1hr (p = 0.004) and 4hrs (p<0.0001). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients. |
format | Online Article Text |
id | pubmed-5325546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53255462017-03-09 Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure Kimulwo, Maureen J. Okendo, Javan Aman, Rashid A. Ogutu, Bernhards R. Kokwaro, Gilbert O. Ochieng, Dorothy J. Muigai, Anne W. T. Oloo, Florence A. Ochieng, Washingtone PLoS One Research Article Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12–156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p = 0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p = 0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3μg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3μg/ml for optimal therapeutic nevirapine level, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p = 0.05) and virologic VF (p = 0.002) in a chi-square test. These mean cNVP levels differed significantly in non-parametric tests between adherence categories at 1hr (p = 0.005) and 4hrs (p = 0.01) and between ART regimen categories at 1hr (p = 0.004) and 4hrs (p<0.0001). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients. Public Library of Science 2017-02-24 /pmc/articles/PMC5325546/ /pubmed/28235021 http://dx.doi.org/10.1371/journal.pone.0172960 Text en © 2017 Kimulwo et al http://creativecommons.org/licenses/by/4.0/ 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 author and source are credited. |
spellingShingle | Research Article Kimulwo, Maureen J. Okendo, Javan Aman, Rashid A. Ogutu, Bernhards R. Kokwaro, Gilbert O. Ochieng, Dorothy J. Muigai, Anne W. T. Oloo, Florence A. Ochieng, Washingtone Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure |
title | Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure |
title_full | Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure |
title_fullStr | Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure |
title_full_unstemmed | Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure |
title_short | Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure |
title_sort | plasma nevirapine concentrations predict virological and adherence failure in kenyan hiv-1 infected patients with extensive antiretroviral treatment exposure |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325546/ https://www.ncbi.nlm.nih.gov/pubmed/28235021 http://dx.doi.org/10.1371/journal.pone.0172960 |
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