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

• Published in: Antiviral therapy Vol. 20; no. 6; pp. 643 - 654
• Main Authors: Boyd, Anders, Moh, Raoul, Gabillard, Delphine, le Carrou, Jérôme, Danel, Christine, Anglaret, Xavier, Eholié, Serge P, Maylin, Sarah, Delaugerre, Constance, Zoulim, Fabien, Girard, Pierre-Marie, Lacombe, Karine
• Format: Journal Article
• Language: English
• Published: England 2015
• Subjects: Adult; Alanine Transaminase - blood; Antiretroviral Therapy, Highly Active; Antiviral Agents - therapeutic use; Aspartate Aminotransferases - blood; Coinfection; Cote d'Ivoire; DNA, Viral - antagonists & inhibitors; DNA, Viral - genetics; Drug Resistance, Viral; Emtricitabine - therapeutic use; Female; Genotype; Hepatitis B e Antigens - blood; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-2 - drug effects; HIV-2 - genetics; Humans; Lamivudine - therapeutic use; Lentivirus; Male; Prospective Studies; Retroviridae; Tenofovir - therapeutic use; Viral Load - drug effects; Cote d'Ivoire
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP2959

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. 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 quantified using an in-house assay (detection limit: <12 copies/ml) while pol and preS/S regions of positive samples were sequenced. 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 <10(5) copies/ml), no incident amino acid changes associated with antiviral resistance were observed. Among 11/127 (8.7%) patients with high-level persistent viraemia (last HBV VL: ≥10(5) 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 flares >120 IU/ml (incidence rate =0.5/100 person-years). 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 benefit from LAM-containing ART with low risk of resistance.