942 
Surveillance of Hepatitis B Virus Mutations during Tenofovir Treatment in HIV/HBV-co-infected Individuals
Jennifer Audsley*1,2,3, Jennifer Audsley*1,2,3, Jennifer Audsley*1,2,3, N Arrafin1, L Yuen4, A Ayres4, S Crowe5, A Bartholomeusz4, S Locarnini4, A Mijch1, S Lewin1,2,3, S Lewin1,2,3, S Lewin1,2,3, J Sasadeusz1,3,6, J Sasadeusz1,3,6, and J Sasadeusz1,3,6
1Alfred Hosp, Melbourne, Australia; 2Monash Univ, Melbourne, Australia; 3Ctr for Clin Res Excellence in Infectious Diseases, Univ of Melbourne, Australia; 4Victorian Infectious Diseases Reference Lab, North Melbourne, Australia; 5The Burnet Inst, Melbourne, Australia; and 6Victorian Infectious Diseases Svc, Melbourne, Australia
Background: Co-infection with HIV and hepatitis B virus
(HBV) is common because of the shared modes of transmission; 7% of HIV-infected
individuals in Australia
are co-infected with HBV. Tenofovir (TDF) is frequently used for management of
HIV and also has potent activity against both wild type and lamivudine
(3TC)-resistant HBV. Most 3TC resistance in HBV has been associated with
combined mutations in HBV reverse transcriptase (rt)L180M
+ rtM204I. Recently, the rtA194T mutation together with the 3TC -resistant
mutations has been associated with TDF resistance. The aim of this study was to
identify and characterize HBV mutations associated with ongoing HBV replication
in individuals receiving TDF±3TC.
Methods: This
retrospective cross-sectional study identified 44 HIV/HBV-co-infected
individuals who had received TDF for at least 3 months at 3 Melbourne tertiary centers. Of these patients,
28 had treatment samples available while receiving TDF (on-TDF), and of those,
24 also had samples available prior to TDF treatment (pre-TDF). Case records were reviewed to obtain data on
age, sex, duration of 3TC and TDF therapy, CD4 counts, serum alanine
aminotransferase levels, HBV serology, HIV viral load, and HBV viral load at
the times of sampling (±3 months). The HBV DNA of all available samples was
amplified using polymerase chain reaction (PCR), and the polymerase region of
PCR-positive samples sequenced and compared with reference HBV sequences.
Results: Of the pre-TDF isolates, 15 of 24 (63%) were
HBV PCR-positive, and 3TC-resistant mutations were identified in 7 of 15 (47%)
of the viremic samples. In the individuals with on-TDF samples 6 of 28 (21%)
were HBV PCR-positive with a mean time on TDF of 15 months (range 3 to 27
months). 3TC-resistant mutations were detected in 4 of 6 (67%) of these viremic
samples. Of the 6 individuals with HBV detected by PCR in the on-TDF samples, 4
had HBV detected by PCR in the pre-TDF sample, and 2
did not have pre-TDF samples available. In the on-TDF treatment samples a
unique polymerase mutation was identified in 1 (3%) at rtK212M. The previously
identified TDF-resistant mutations at rtA194T + rtL180M + rtM204V were not
detected in any on-TDF sample.
Conclusions: Unique mutations associated with TDF
resistance are rare in HIV/HBV co-infection. 3TC-resistant mutations persist,
and a fifth of patients are HBV PCR-positive despite the addition of TDF. One novel
mutation was identified in HBV isolated from a patient during TDF treatment.
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