A Abdissa1,2, M F Olsen3, D Yilma4, M Tesfaye5, T Girma6, M Christiansen7, C M Hagen7, L Wiesner8, S Castel8, A Aseffa9, H McIlleron8, C Pedersen2, H Friis3, A B Andersen2. 1. Department of Medical Laboratory Sciences & Pathology, Jimma University, Jimma, Ethiopia. 2. Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. 3. Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. 4. Department of Internal Medicine, Jimma University, Jimma, Ethiopia. 5. Department of Psychiatry, Jimma University, Jimma, Ethiopia. 6. Department of Pediatrics and Child Health, Jimma University, Jimma, Ethiopia. 7. Department of Clinical Biochemistry and Immunology, Statens Serum Institute, Copenhagen, Denmark. 8. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa. 9. Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Abstract
OBJECTIVES: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.
RCT Entities:
OBJECTIVES: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-infectedpatients. 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: Jane Mallewa; Alexander J Szubert; Peter Mugyenyi; Ennie Chidziva; Margaret J Thomason; Priscilla Chepkorir; George Abongomera; Keith Baleeta; Anthony Etyang; Colin Warambwa; Betty Melly; Shepherd Mudzingwa; Christine Kelly; Clara Agutu; Helen Wilkes; Sanele Nkomani; Victor Musiime; Abbas Lugemwa; Sarah L Pett; Mutsa Bwakura-Dangarembizi; Andrew J Prendergast; Diana M Gibb; A Sarah Walker; James A Berkley Journal: Lancet HIV Date: 2018-04-10 Impact factor: 16.070