TY - JOUR
T1 - Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa
AU - the ANRS 12240 VarBVA study
AU - Boyd, Anders
AU - Moh, Raoul
AU - Maylin, Sarah
AU - Abdou Chekaraou, Mariama
AU - Mahjoub, Nadia
AU - Gabillard, Delphine
AU - Anglaret, Xavier
AU - Eholié, Serge Paul
AU - Danel, Christine
AU - Delaugerre, Constance
AU - Zoulim, Fabien
AU - Lacombe, Karine
N1 - Funding Information: Funding information This study was supported by the Agence Nationale de Recherche sur le Sida et les H?patites (ANRS 12240). A.B. was awarded a post-doctoral fellowship from the ANRS and SIDACTION. We thank all patients who participated in both trials. We also gratefully acknowledge the valuable contributions of the SMIT, CeDReS, CEPREF, USAC, CIRBA, CNTS, La Pierre Angulaire, H?pital G?n?ral Abobo, Formation Sanitaire Anonkoua Kout?, Centre de sant? El Rapha, the Programme PACCI team, as well as the INSERM exU593 and U897 teams; Bristol-Myers Squibb for providing Zerit and Videx; Gilead Sciences, for the donation of Truvada; and Merck Sharp & Dohme, for the donation of Stocrin. Publisher Copyright: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2019/2
Y1 - 2019/2
N2 - Background & Aims: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. Methods: Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. Results: Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B “e” antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). Conclusion: Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.
AB - Background & Aims: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. Methods: Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. Results: Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B “e” antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). Conclusion: Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.
KW - genetic variability
KW - hepatitis B surface antigen
KW - immunosuppression
KW - surface gene
UR - http://www.scopus.com/inward/record.url?scp=85055045537&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/liv.13975
DO - https://doi.org/10.1111/liv.13975
M3 - Article
C2 - 30257068
SN - 1478-3223
VL - 39
SP - 280
EP - 289
JO - Liver international
JF - Liver international
IS - 2
ER -