title: Lipid-based nutrient supplements do not affect efavirenz but lower plasma nevirapine concentrations in Ethiopian adult HIV patients.
abstract: OBJECTIVE
  Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients.
  
  
  METHODS
  The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS containing whey (LNS/w), an LNS containing soy (LNS/s) or no LNS. Trough plasma concentrations of efavirenz and nevirapine were measured at 1 and 2 months. Genotyping for 516 G>T and 983 T>C polymorphisms of the cytochrome P450 (CYP) 2B6 locus was performed. Multilevel linear mixed-effects models were used to assess the associations between LNS and plasma efavirenz and nevirapine concentrations.
  
  
  RESULTS
  In patients with BMI > 17 kg/m(2), nevirapine concentrations were lower in the LNS/w and LNS/s groups by a median of -2.3 μg/mL [interquartile range (IQR) -3.9; -0.9 μg/mL; P = 0.002] and -2.1 μg/mL (IQR -3.9; -0.9 μg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 μg/mL higher plasma efavirenz concentration compared with the wild type (P < 0.0001), while it was not associated with plasma nevirapine concentrations.
  
  
  CONCLUSIONS
  Intake of an LNS was associated with lower plasma nevirapine trough concentrations, indicating possible drug-LNS interactions. The clinical relevance of such reductions in nevirapine exposure is not clear. Plasma efavirenz concentration was not affected by the LNS.
authors.affiliation: Department of Medical Laboratory Sciences & Pathology, Jimma University, Jimma, Ethiopia.|Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Abdissa
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M F
authors.initials: MF
authors.lastname: Olsen
authors.affiliation: Department of Internal Medicine, Jimma University, Jimma, Ethiopia.
authors.forename: D
authors.initials: D
authors.lastname: Yilma
authors.affiliation: Department of Psychiatry, Jimma University, Jimma, Ethiopia.
authors.forename: M
authors.initials: M
authors.lastname: Tesfaye
authors.affiliation: Department of Pediatrics and Child Health, Jimma University, Jimma, Ethiopia.
authors.forename: T
authors.initials: T
authors.lastname: Girma
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen, Denmark.
authors.forename: C M
authors.initials: CM
authors.lastname: Hagen
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Wiesner
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Castel
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors.forename: A
authors.initials: A
authors.lastname: Aseffa
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: H
authors.initials: H
authors.lastname: McIlleron
authors.affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Friis
authors.affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: A B
authors.initials: AB
authors.lastname: Andersen
mesh_terms: D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000097:blood / Q000627:therapeutic use*; D044383:Black People; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000097:blood; D019587:Dietary Supplements; D005002:Ethiopia / Q000453:epidemiology; D005228:Fatty Acids, Essential / Q000008:administration & dosage*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000097:blood; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage; D019829:Nevirapine / Q000097:blood* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000097:blood* / Q000627:therapeutic use; D014505:Urban Population
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D005228:Fatty Acids, Essential; D008055:Lipids; D018977:Micronutrients; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz
keywords: efavirenz; lipid-based nutrient supplement; nevirapine; nonnucleoside reverse transcriptase inhibitors