Prolonged use of tenofovir in HIV/hepatitis B virus (HBV)-coinfected individuals does not lead to HBV polymerase mutations and is associated with persistence of lamivudine HBV polymerase mutations.
OBJECTIVE
The aim of the study was to identify and characterize hepatitis B virus (HBV) polymerase gene mutations associated with ongoing HBV replication in HIV/HBV-coinfected individuals receiving tenofovir (TDF).


METHODS
This retrospective cross-sectional study identified 28 HIV/HBV-coinfected individuals who had received TDF for at least 3 months. All patients had samples available while receiving TDF (on-TDF), and 24 also had samples available prior to treatment (pre-TDF). Case records were reviewed to obtain clinical and virological data at the times of sampling (+/-3 months). The HBV DNA of all samples was amplified using polymerase chain reaction (PCR), and the polymerase region of PCR-positive samples was sequenced and compared with reference HBV data.


RESULTS
Of the pre-TDF samples, 15 of 24 (63%) were HBV PCR positive. Of the on-TDF samples, four of 28 (14%) were HBV PCR positive (mean time on TDF 13.5 months; range 3-23 months). Lamivudine (3TC)-resistance mutations were detected in three of four (75%) of these viraemic samples. The previously identified putative TDF-resistance mutations, rtA194T+rtL180M+rtM204V, were not detected in any individual.


CONCLUSIONS
Unique mutations in the HBV polymerase gene associated with TDF resistance are rare in HIV/HBV coinfection. 3TC-resistance mutations persist and a significant proportion of patients are HBV PCR positive despite the addition of TDF.
Audsley
J
J
Monash University, Melbourne, VIC, Australia.
Arrifin
N
N
Yuen
L K W
LK
Ayres
A
A
Crowe
S M
SM
Bartholomeusz
A
A
Locarnini
S A
SA
Mijch
A
A
Lewin
S R
SR
Sasadeusz
J
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015684:Gene Products, pol / Q000187:drug effects / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006509:Hepatitis B / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D000068698:Tenofovir; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D000998:Antiviral Agents; D015684:Gene Products, pol; D063065:Organophosphonates; C066027:P protein, Hepatitis B virus; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine