Timothy Archampong1, Oluwayemisi Ojewale2, Kristi Bears3, Yiqing Chen3, Margaret Lartey1, Kwamena W Sagoe4, Adjoa Obo-Akwa1, Yan Gong3,5, Taimour Langaee3, Awewura Kwara2. 1. Department of Medicine and Therapeutics, University of Ghana School of Medicine and Dentistry, Korle-Bu Teaching Hospital, Accra, Ghana. 2. Department of Medicine, College of Medicine, University of Florida, Gainesville, FL. 3. Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL. 4. Department of Microbiology, School of Biomedical and Allied Health Sciences, Accra, Ghana. 5. UF Health Cancer Center, University of Florida, Gainesville, FL.
Abstract
BACKGROUND: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfected patients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. METHODS: HIV/HBV coinfected patients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined. RESULTS: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1-7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4 rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4 rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4 rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA. CONCLUSIONS: We identified a novel association between ABCC4 rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.
BACKGROUND: Incomplete hepatitis B virus (HBV) suppression during antiretroviral therapy (ART) in HIV and HBV coinfectedpatients is common, but underlying factors are not fully elucidated. We hypothesize that genetic factors that influence nucleoside analog pharmacokinetics will affect HBV treatment response. METHODS:HIV/HBV coinfectedpatients on tenofovir disoproxil fumarate/lamivudine (TDF/3TC)-containing ART were enrolled. Selected ABCC4 single nucleotide polymorphisms (SNPs) with known effects on nucleoside pharmacokinetics were genotyped using TaqMan assays. Relationship between ABCC4 SNPs and unsuppressed HBV DNA (HBV DNA ≥20 IU/mL) were examined. RESULTS: Of the 50 participants on TDF/3TC-containing ART for a median (range) of 1.5 (1-7.4) years, 20 (40%) had unsuppressed HBV DNA. Participants with unsuppressed compared with those with suppressed HBV DNA were more likely to have negative HBe antibody, lower body mass index, and lower CD4 count at enrollment. Carriers of ABCC4rs11568695 (G3724A) variant allele were more likely than noncarriers to have unsuppressed HBV (61.1% vs. 29.0%, P = 0.038). Among 36 patients with suppressed HIV RNA (presumed good ART adherence), ABCC4rs11568695 variant carriers were more likely than noncarriers to have unsuppressed HBV (58.8% vs. 20.0% P = 0.021). Logistic regression analysis that included genetic and nongenetic factors identified ABCC4rs11568695 variant allele, body mass index, and male sex as predictors of unsuppressed HBV DNA. CONCLUSIONS: We identified a novel association between ABCC4rs11568695 SNP and poor HBV treatment response. If confirmed in further studies, ABCC4 genotyping could be used to identify individuals who may need intensified HBV therapy.
Authors: Kasha P Singh; Megan Crane; Jennifer Audsley; Anchalee Avihingsanon; Joe Sasadeusz; Sharon R Lewin Journal: AIDS Date: 2017-09-24 Impact factor: 4.177
Authors: Valentine Wanga; Charles Venuto; Gene D Morse; Edward P Acosta; Eric S Daar; David W Haas; Chun Li; Bryan E Shepherd Journal: Pharmacogenet Genomics Date: 2015-09 Impact factor: 2.089
Authors: J D Schuetz; M C Connelly; D Sun; S G Paibir; P M Flynn; R V Srinivas; A Kumar; A Fridland Journal: Nat Med Date: 1999-09 Impact factor: 53.440
Authors: Adrian S Ray; Tomas Cihlar; Kelly L Robinson; Leah Tong; Jennifer E Vela; Michael D Fuller; Lani M Wieman; Eugene J Eisenberg; Gerry R Rhodes Journal: Antimicrob Agents Chemother Date: 2006-10 Impact factor: 5.191
Authors: Chloe L Thio; Eric C Seaberg; Richard Skolasky; John Phair; Barbara Visscher; Alvaro Muñoz; David L Thomas Journal: Lancet Date: 2002-12-14 Impact factor: 79.321
Authors: Jennifer J Kiser; Christina L Aquilante; Peter L Anderson; Tracy M King; Monica L Carten; Courtney V Fletcher Journal: J Acquir Immune Defic Syndr Date: 2008-03-01 Impact factor: 3.731
Authors: A Fuchs; N Lübke; L Schmidt; B-E O Jensen; A Walker; V Keitel-Anselmino; V di Cristanziano; M Böhm; E Knops; E Heger; R Kaiser; A de Luca; M Oette; D Häussinger; J Timm Journal: Infection Date: 2021-02-03 Impact factor: 3.553