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.
National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia. gmatthews@nchecr.unsw.edu.au
Gail V
GV
Matthews
Angeline
A
Bartholomeusz
Stephen
S
Locarnini
Anna
A
Ayres
Joe
J
Sasaduesz
Eric
E
Seaberg
David A
DA
Cooper
Sharon
S
Lewin
Gregory J
GJ
Dore
Chloe L
CL
Thio
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