Low risk of lamivudine-resistant HBV and hepatic lares in treated HIV-HBV-coinfected patients from Côte d'Ivoire

Background: In HIV-HBV-coinfected patients from sub-Saharan Africa, incidence of antiviral resistant HBV-mutations after initiating long-term antiretroviral therapy (ART) has only been evaluated in limited patient populations. Methods: In this nested, prospective cohort study from two randomized controlled trials in Côte d'Ivoire, 168 ART-naive HIV-HBV-coinfected patients, starting lamivudine (LAM, n=82) or tenofovir/emtricitabine (TDF/FTC, n=86) containing ART were included. HBV DNA viral load (VL) was quantiied using an in-house assay (detection limit: <12 copies/ml) while pol and preS/S regions of positive samples were sequenced. Results: At ART-initiation, 39 (23.2%) were hepatitis B e antigen-positive, 53 (31.5%) had alanine or aspartate aminotransferase levels >40 IU/ml and 98/100 (98.0%) harboured genotype E. Among the 127 (75.6%) patients with detectable baseline HBV VL (median 4.27 log10 copies/ml, IQR 3.14-7.64), cumulative percentage achieving undetectable HBV DNA was 74.2% for patients undergoing LAM-containing ART and 94.2% for TDF/FTC-containing ART after a median 35.5 months (IQR 24.3-36.5). No baseline antiviral resistance mutations were observed. Among 28/127 (22.1%) patients with low-level persistent viraemia (last HBV VL: between 12 to <105 copies/ml), no incident amino acid changes associated with antiviral resistance were observed. Among 11/127 (8.7%) patients with highlevel persistent viraemia (last HBV VL: ≥105 copies/ml), only two harboured incident LAM-resistance mutations at positions rtV173L+rtL180M+rtM204V with no patient exhibiting TDF/FTC-resistance. Two patients had transaminase lares >120 IU/ml (incidence rate =0.5/100 person-years). Conclusions: Antiviral resistance, particularly to LAM, was remarkably rare in this cohort of HIV-HBV-coinfected patients. Further research is needed to determine which coinfected populations might beneit from LAM-containing ART with low risk of resistance.