title: Low risk of lamivudine-resistant HBV and hepatic flares in treated HIV-HBV-coinfected patients from Côte d'Ivoire.
abstract: 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 quantified 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 <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).
  
  
  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 benefit from LAM-containing ART with low risk of resistance.
authors: INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France. anders.boyd@upmc.fr.
authors: Anders
authors: A
authors: Boyd
authors: Raoul
authors: R
authors: Moh
authors: Delphine
authors: D
authors: Gabillard
authors: Jérôme
authors: J
authors: le Carrou
authors: Christine
authors: C
authors: Danel
authors: Xavier
authors: X
authors: Anglaret
authors: Serge P
authors: SP
authors: Eholié
authors: Sarah
authors: S
authors: Maylin
authors: Constance
authors: C
authors: Delaugerre
authors: Fabien
authors: F
authors: Zoulim
authors: Pierre-Marie
authors: PM
authors: Girard
authors: Karine
authors: K
authors: Lacombe
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D060085:Coinfection; D007560:Cote d'Ivoire; D004279:DNA, Viral / Q000037:antagonists & inhibitors* / Q000235:genetics; D024882:Drug Resistance, Viral; D000068679:Emtricitabine / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D015498:HIV-2 / Q000187:drug effects / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D000068698:Tenofovir / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000068698:Tenofovir; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000068679:Emtricitabine