Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy.
BACKGROUND
Little is known about the prevalence and pattern of hepatitis B virus (HBV) mutations in HIV/HBV co-infected individuals on long-term lamivudine (3TC) therapy.


METHODS
HBV polymerase/envelope/basal core promoter/pre-core sequences from 81 HIV-HBV co-infected persons who received at least 6 months 3TC were compared to HBV reference sequences. Host and viral characteristics associated with HBV mutations were determined.


RESULTS
HBV viraemia was detected in 53 persons (65%) and was associated with lower CD4 cell count nadir and higher HIV RNA at the time of testing but not with 3TC duration. Known 3TC-resistant mutations occurred in 50% and 94% of viremic patients with < 2 years and > 4 years 3TC, respectively. The CD4 cell count at testing was significantly higher in those with 3TC-resistant mutations. The triple polymerase mutant (rtL173V, rtL180M, rtM204V), which behaves as a vaccine escape mutant in vitro, occurred in 17% of viraemic patients. Polymerase mutations that may confer resistance to other anti-HBV agents were also detected.


CONCLUSIONS
In HIV-HBV co-infected patients, greater immunocompromise is associated with continued HBV viraemia while on 3TC, and development of 3TC-resistant mutations are inevitable with prolonged 3TC use. These mutant viruses may limit future therapeutic options due to cross-resistance or may produce HBV vaccine escape mutants. Thus, timing and selection of antiretroviral therapy is critical in this population.
Matthews
Gail V
GV
National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia. gmatthews@nchecr.unsw.edu.au
Bartholomeusz
Angeline
A
Locarnini
Stephen
S
Ayres
Anna
A
Sasaduesz
Joe
J
Seaberg
Eric
E
Cooper
David A
DA
Lewin
Sharon
S
Dore
Gregory J
GJ
Thio
Chloe L
CL
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006509:Hepatitis B / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007108:Immune Tolerance; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014759:Viral Envelope Proteins / Q000235:genetics; D019562:Viral Load; D014766:Viremia / Q000821:virology
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D014759:Viral Envelope Proteins; D019259:Lamivudine