Precore G1896A mutation is associated with reduced rates of HBsAg-seroclearance in treated HIV-hepatitis B virus co-infected patients from Western Africa Running title: Precore G1896A mutations in SSA
Résumé
The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)‐infected patients. Whether this mutation affects the therapeutic course of HIV‐HBV co‐infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)‐naïve HIV‐HBV co‐infected patients from Côte d'Ivoire, initiating ARV‐treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV‐DNA, hepatitis B “e” antigen (HBeAg) seroclearance (in HBeAg‐positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV‐initiation, median HBV‐DNA was 6.04 log10 copies/mL (IQR = 3.70‐7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg‐negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24‐36). Cumulative proportion of undetectable HBV‐DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV‐DNA levels and anti‐HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti‐HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.
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