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)-naive HIV-HBV co-infected patients from Cote 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% harboring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg-negative (p<0.001) and had basal core promotor A1762T/ G1764A mutations (p<0.001). 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% versus no pcG1896A=66.9%, p=0.04), but not after adjusting for baseline HBV-DNA levels and anti-HBV agent (p=0.2). No difference in cumulative proportion of HBeAg-seroclearance was observed between mutation groups (pcG1896A=57.1% versus no pcG1896A=54.3%, p=0.7). Significantly higher cumulative proportion of HBsAg-seroclearance was observed in patients without this mutation (pcG1896A=0% versus no pcG1896A=36.9%, p<0.001), even after adjusting for baseline HBsAg-quantification and anti-HBV agent (p<0.001). 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.< Réduire