Open AccessPrevalence and risk factors for efavirenz-based antiretroviral treatment–associated severe vitamin D deficiency
Author(s) -
Hanylén,
Abiy Habtewold,
Eyasu Makonnen,
Getnet Yimer,
Leif Bertilsson,
Jürgen Burhenne,
Ulf Diczfalusy,
Eleni Aklillu
Publication year - 2016
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000004631
Subject(s) - efavirenz , medicine , cart , tuberculosis , gastroenterology , rifampicin , vitamin d and neurology , vitamin d deficiency , viral load , human immunodeficiency virus (hiv) , immunology , antiretroviral therapy , pathology , mechanical engineering , engineering
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.