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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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2016 Aug 26
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| In: |
Medicine
Year: 2016, Volume: 95, Issue: 34, Pages: e4631 |
| ISSN: | 1536-5964 |
| DOI: | 10.1097/MD.0000000000004631 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1097/MD.0000000000004631 Verlag, lizenzpflichtig, Volltext: https://journals.lww.com/md-journal/Fulltext/2016/08230/Prevalence_and_risk_factors_for_efavirenz_based.38.aspx 
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| Author Notes: | Hanna Nylén, PhD, Abiy Habtewold, PhD, Eyasu Makonnen, PhD, Getnet Yimer, PhD, Leif Bertilsson, PhD, Jürgen Burhenne, PhD, Ulf Diczfalusy, PhD, Eleni Aklillu, PhD |
| Summary: | 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, 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 4β-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. |
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| Item Description: | Gesehen am 03.07.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1536-5964 |
| DOI: | 10.1097/MD.0000000000004631 |