PREVALENCE AND RISK FACTORS FOR EFAVIRENZ-BASED ANTIRETROVIRAL TREATMENT-ASSOCIATED SEVERE VITAMIN D DEFICIENCY: A PROSPECTIVE COHORT STUDY

Abstract

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-naive 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, 4th, 16th, and 48th week of cART. Plasma efavirenz concentrations were determined at 4th and 16th weeks of cART. TB-HIV patients had significantly lower plasma 25 (OH)D3 levels than HIV-only patients at baseline. TB co-infection, low Karnofsky score, high viral load, and high CYP3A activity as measured by plasma 4b-hydroxycholesterol/cholesterol ratios were significant predictors of low 25 (OH)D3 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 4th, 16th, and 48th weeks of cART, respectively. The median 25 (OH)D3 levels declined from baseline by 40%, 50%, and 14% at 4th, 16th, and 48th weeks of cART, respectively. In TB-HIV patients, previous anti-TB therapy had no influence on 25 (OH)D3 levels, but the initiation of efavirenz-based cART increased the prevalence of SVDD from 57% at baseline to 70% and 72% at the 4th and 16th weeks of cART, respectively. Median plasma 25 (OH)D3 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)D3 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.© Copyright 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.