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Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study

Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We inv...

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Autores principales: Nylén, Hanna, Habtewold, Abiy, Makonnen, Eyasu, Yimer, Getnet, Bertilsson, Leif, Burhenne, Jürgen, Diczfalusy, Ulf, Aklillu, Eleni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400328/
https://www.ncbi.nlm.nih.gov/pubmed/27559961
http://dx.doi.org/10.1097/MD.0000000000004631
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author Nylén, Hanna
Habtewold, Abiy
Makonnen, Eyasu
Yimer, Getnet
Bertilsson, Leif
Burhenne, Jürgen
Diczfalusy, Ulf
Aklillu, Eleni
author_facet Nylén, Hanna
Habtewold, Abiy
Makonnen, Eyasu
Yimer, Getnet
Bertilsson, Leif
Burhenne, Jürgen
Diczfalusy, Ulf
Aklillu, Eleni
author_sort Nylén, Hanna
collection PubMed
description Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD. Treatment-naïve Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV coinfected patients, rifampicin-based anti-TB treatment was initiated 4 or 8 weeks before starting cART. Plasma 25-hydroxyvitamin D (25 [OH]D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, 4(th), 16(th), and 48(th) week of cART. Plasma efavirenz concentrations were determined at 4(th) and 16(th) weeks of cART. TB-HIV patients had significantly lower plasma 25 (OH)D(3) levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load, and high CYP3A activity as measured by plasma 4β-hydroxycholesterol/cholesterol ratios were significant predictors of low 25 (OH)D(3) levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79%, and 43% at 4(th), 16(th), and 48(th) weeks of cART, respectively. The median 25 (OH)D(3) levels declined from baseline by −40%, −50%, and −14% at 4(th), 16(th), and 48(th) weeks of cART, respectively. In TB-HIV patients, previous anti-TB therapy had no influence on 25 (OH)D(3) levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at the 4(th) and 16(th) weeks of cART, respectively. Median plasma 25 (OH)D(3) declined from baseline by −17% and −21% at week 4 and 16 of cART, respectively. Our results indicate low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations as significant predictors of early efavirenz-based cART-induced vitamin D deficiency. Low plasma 25 (OH)D(3) level at baseline is associated with TB co-infection and HIV diseases progression. Initiation of efavirenz-based cART is associated with high incidence of SVDD, whereas rifampicin based anti-TB therapy co-treatment has no significant effect. Supplementary vitamin D during cART initiation may be beneficial for HIV patients regardless of TB coinfection.
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spelling pubmed-54003282017-04-27 Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study Nylén, Hanna Habtewold, Abiy Makonnen, Eyasu Yimer, Getnet Bertilsson, Leif Burhenne, Jürgen Diczfalusy, Ulf Aklillu, Eleni Medicine (Baltimore) 4850 Initiation of efavirenz-based combination antiretroviral therapy (cART) is associated with Vitamin D deficiency, but the risk factors including efavirenz pharmacokinetics for cART-induced severe vitamin D deficiency (SVDD) and the impact of anti-tuberculosis (TB) cotreatment are not explored. We investigated the prevalence of SVDD in HIV and TB-HIV coinfected patients and associated risk factors for treatment-induced SVDD. Treatment-naïve Ethiopian HIV patients with (n = 102) or without (n = 89) TB co-infection were enrolled prospectively and received efavirenz-based cART. In TB-HIV coinfected patients, rifampicin-based anti-TB treatment was initiated 4 or 8 weeks before starting cART. Plasma 25-hydroxyvitamin D (25 [OH]D), cholesterol and 4-beta hydroxycholesterol concentrations were measured at baseline, 4(th), 16(th), and 48(th) week of cART. Plasma efavirenz concentrations were determined at 4(th) and 16(th) weeks of cART. TB-HIV patients had significantly lower plasma 25 (OH)D(3) levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load, and high CYP3A activity as measured by plasma 4β-hydroxycholesterol/cholesterol ratios were significant predictors of low 25 (OH)D(3) levels at baseline. In HIV-only patients, initiation of efavirenz-based cART increased the prevalence of SVVD from 27% at baseline to 76%, 79%, and 43% at 4(th), 16(th), and 48(th) weeks of cART, respectively. The median 25 (OH)D(3) levels declined from baseline by −40%, −50%, and −14% at 4(th), 16(th), and 48(th) weeks of cART, respectively. In TB-HIV patients, previous anti-TB therapy had no influence on 25 (OH)D(3) levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at the 4(th) and 16(th) weeks of cART, respectively. Median plasma 25 (OH)D(3) declined from baseline by −17% and −21% at week 4 and 16 of cART, respectively. Our results indicate low plasma cholesterol, high CYP3A activity, and high plasma efavirenz concentrations as significant predictors of early efavirenz-based cART-induced vitamin D deficiency. Low plasma 25 (OH)D(3) level at baseline is associated with TB co-infection and HIV diseases progression. Initiation of efavirenz-based cART is associated with high incidence of SVDD, whereas rifampicin based anti-TB therapy co-treatment has no significant effect. Supplementary vitamin D during cART initiation may be beneficial for HIV patients regardless of TB coinfection. Wolters Kluwer Health 2016-08-26 /pmc/articles/PMC5400328/ /pubmed/27559961 http://dx.doi.org/10.1097/MD.0000000000004631 Text en Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0 This is an open access article distributed under the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0
spellingShingle 4850
Nylén, Hanna
Habtewold, Abiy
Makonnen, Eyasu
Yimer, Getnet
Bertilsson, Leif
Burhenne, Jürgen
Diczfalusy, Ulf
Aklillu, Eleni
Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study
title Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study
title_full Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study
title_fullStr Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study
title_full_unstemmed Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study
title_short Prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency: A prospective cohort study
title_sort prevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin d deficiency: a prospective cohort study
topic 4850
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5400328/
https://www.ncbi.nlm.nih.gov/pubmed/27559961
http://dx.doi.org/10.1097/MD.0000000000004631
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