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Brief Report

Relationship Between ABCC4 SNPs and Hepatitis B Virus Suppression During Tenofovir-Containing Antiretroviral Therapy in Patients With HIV/HBV Coinfection

Archampong, Timothy MBChB, FWACP, FRCPa; Ojewale, Oluwayemisi MBChB, MPHb; Bears, Kristi BSc; Chen, Yiqing MSc; Lartey, Margaret MBChB, MPH, FWACPa; Sagoe, Kwamena W. PhDd; Obo-Akwa, Adjoa BSc, MPHa; Gong, Yan PhD, MSc,e; Langaee, Taimour PhDc; Kwara, Awewura MD, MPH&TMb

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1, 2019 - Volume 82 - Issue 4 - p 421–425
doi: 10.1097/QAI.0000000000002136
Translational Research
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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.

aDepartment of Medicine and Therapeutics, University of Ghana School of Medicine and Dentistry, Korle-Bu Teaching Hospital, Accra, Ghana;

bDepartment of Medicine, College of Medicine, University of Florida, Gainesville, FL;

cDepartment of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL;

dDepartment of Microbiology, School of Biomedical and Allied Health Sciences, Accra, Ghana; and

eUF Health Cancer Center, University of Florida, Gainesville, FL.

Correspondence to: Awewura Kwara, University of Florida College of Medicine, Emerging Pathogens Institute, 2055 Mowry Road, P.O. Box 103600, Gainesville, FL 32610 (e-mail: awewura.kwara@medicine.ufl.edu).

Supported in part by the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine. The initial study that obtained the DNA samples was funded by a Developmental Grant from the Lifespan/Tufts/Brown CFAR (P30AI042853) to T.A. A.K. received support from Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health [grant number HD071779] and Fogarty International Center [grant number TW010055].

The authors have no conflicts of interest to disclose.

T.A., M.L., and A.K. contributed to the study design of the initial study, acquisition of data, analysis and interpretation of data, and drafting of the manuscript. O.O., T.L., and A.K. contributed to design of the current study and acquisition of data for the current analysis. K.W.S. and A.O.-A. contributed to acquisition of clinical and laboratory data. K.B. and T.L. performed DNA genotyping. Y.C. and Y.G. contributed to statistical analysis, drafting of the manuscript. All authors critically reviewed the manuscript and approved the final version.

Received April 22, 2019

Accepted June 24, 2019

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