TY - JOUR
T1 - Relationship Between ABCC4 SNPs and Hepatitis B Virus Suppression During Tenofovir-Containing Antiretroviral Therapy in Patients With HIV/HBV Coinfection
AU - Archampong, Timothy
AU - Ojewale, Oluwayemisi
AU - Bears, Kristi
AU - Chen, Yiqing
AU - Lartey, Margaret
AU - Sagoe, Kwamena W.
AU - Obo-Akwa, Adjoa
AU - Gong, Yan
AU - Langaee, Taimour
AU - Kwara, Awewura
N1 - Publisher Copyright:
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - ABCC4 single nucleotide polymorphisms
KW - Antiretroviral therapy
KW - HBV suppression
KW - HIV/HBV coinfection
KW - Tenofovir disoproxil fumarate
UR - http://www.scopus.com/inward/record.url?scp=85074245666&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000002136
DO - 10.1097/QAI.0000000000002136
M3 - Article
C2 - 31335591
AN - SCOPUS:85074245666
SN - 1525-4135
VL - 82
SP - 421
EP - 425
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -