TY - JOUR
T1 - Low incidence of precore W28* mutant variants in treated hepatitis B virus and human immunodeficiency virus co-infected patients
AU - Boyd, Anders
AU - Lacombe, Karine
AU - Lavocat, Fabien
AU - Miailhes, Patrick
AU - Lascoux-Combe, Caroline
AU - Girard, Pierre Maire
AU - Zoulim, Fabien
N1 - Funding Information: This study has been funded in part by Sidaction (AO 19) and received additional grants from ANRS (Agence Nationale de Recherche sur le Sida et les Hépatites). Gilead Sciences, Inc. and Roche Diagnostics provided unrestricted grants for the French HIV-HBV Cohort Study. Both Gilead Sciences, Inc. and Roche Diagnostics were not involved in any part of the data collection, analysis, and manuscript writing. AB was awarded post-doctoral fellowships from the ANRS and Sidaction. Funding Information: This study has been funded in part by Sidaction (AO 19) and received additional grants from ANRS (Agence Nationale de Recherche sur le Sida et les Hépatites). Gilead Sciences, Inc. and Roche Diagnostics provided unrestricted grants for the French HIV-HBV Cohort Study. Both Gilead Sciences, Inc. and Roche Diagnostics were not involved in any part of the data collection, analysis, and manuscript writing. AB was awarded post-doctoral fellowships from the ANRS and Sidaction. Publisher Copyright: © 2017 Elsevier B.V.
PY - 2018/1
Y1 - 2018/1
N2 - The precore (pc) W28* mutation arises from immune-selective pressures during the hepatitis B “e” antigen (HBeAg)-positive phase of chronic hepatitis B virus (HBV) infection and has been linked to severe liver-related morbidity. Here, we examined the determinants of harboring this mutation and its rate of emergence in treated patients co-infected with human immunodeficiency virus (HIV) and HBV. In a three-year prospective cohort of 165 HIV-HBV co-infected patients, pcW28* mutation was determined via DNA-chip during yearly sampling. In a subgroup with liver biopsies, HBV covalently-closed circular (ccc)-DNA and total intrahepatic (IH)-DNA were quantified by real-time PCR. From respective inclusion to year-3 visits, median HBV-DNA levels decreased (5.88 log10 IU/mL to <1.78 log10 IU/mL, p < 0.001) and tenofovir-use increased (15.8%–71.4%, p < 0.001). At baseline, 47 of 162 (29.0%) patients had the pcW28* mutation and were more frequently HBeAg-negative (adjusted-OR = 4.37, 95%CI = 1.76–10.86) and had non-A HBV genotypes (adjusted-OR = 9.14, 95%CI = 4.05–20.66). No association with HIV-related factors was observed. In 114 patients without baseline mutation and available data, four developed incident pcW28* mutation by the end of follow-up (cumulative 3.5%, 95%CI = 1.3–9.1%). In the 32 patients with liver biopsies, 10 (31.3%) patients harboring the pcW28* mutation had significantly lower adjusted mean cccDNA (0.05 versus without = 0.43 copies/cell, p < 0.001) and total IH-DNA levels (2.31 versus without = 18.59 copies/cell, p = 0.006). In conclusion, the pcW28* mutation infrequently appeared in this co-infected study population with increased use of potent antivirals and suppressed levels of circulating virus.
AB - The precore (pc) W28* mutation arises from immune-selective pressures during the hepatitis B “e” antigen (HBeAg)-positive phase of chronic hepatitis B virus (HBV) infection and has been linked to severe liver-related morbidity. Here, we examined the determinants of harboring this mutation and its rate of emergence in treated patients co-infected with human immunodeficiency virus (HIV) and HBV. In a three-year prospective cohort of 165 HIV-HBV co-infected patients, pcW28* mutation was determined via DNA-chip during yearly sampling. In a subgroup with liver biopsies, HBV covalently-closed circular (ccc)-DNA and total intrahepatic (IH)-DNA were quantified by real-time PCR. From respective inclusion to year-3 visits, median HBV-DNA levels decreased (5.88 log10 IU/mL to <1.78 log10 IU/mL, p < 0.001) and tenofovir-use increased (15.8%–71.4%, p < 0.001). At baseline, 47 of 162 (29.0%) patients had the pcW28* mutation and were more frequently HBeAg-negative (adjusted-OR = 4.37, 95%CI = 1.76–10.86) and had non-A HBV genotypes (adjusted-OR = 9.14, 95%CI = 4.05–20.66). No association with HIV-related factors was observed. In 114 patients without baseline mutation and available data, four developed incident pcW28* mutation by the end of follow-up (cumulative 3.5%, 95%CI = 1.3–9.1%). In the 32 patients with liver biopsies, 10 (31.3%) patients harboring the pcW28* mutation had significantly lower adjusted mean cccDNA (0.05 versus without = 0.43 copies/cell, p < 0.001) and total IH-DNA levels (2.31 versus without = 18.59 copies/cell, p = 0.006). In conclusion, the pcW28* mutation infrequently appeared in this co-infected study population with increased use of potent antivirals and suppressed levels of circulating virus.
KW - Genetic variability
KW - Immunosuppression
KW - Precore G1896A mutation
KW - Serological response
KW - Viral replication
UR - http://www.scopus.com/inward/record.url?scp=85036561428&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.antiviral.2017.11.014
DO - https://doi.org/10.1016/j.antiviral.2017.11.014
M3 - Article
C2 - 29169914
SN - 0166-3542
VL - 149
SP - 174
EP - 178
JO - Antiviral Research
JF - Antiviral Research
ER -