HIV and Hepatitis.com Coverage of the
14th Annual Conference on Retroviruses
and Opportunistic Infections (14th CROI)
February 25 - 28, 2007, Los Angeles, CA

Emergence of Tenofovir-resistant Mutations Is Uncommon in HIV-HBV Coinfected Patients

Several antiviral agents -- including 3TC (lamivudine; Epivir) and tenofovir (Viread) -- are active against both HIV and hepatitis B virus (HBV), and it is recommended that HIV-HBV coinfected patients should include such agents in their combination anti-HIV regimens. However, regimens that include only a single agent with anti-HBV activity can promote the emergence of drug-resistant HBV.

As reported at the 14th Conference on Retroviruses and Opportunistic Infections in February, Australian researchers conducted a study to identify and characterize HBV mutations associated with ongoing HBV replication in individuals receiving tenofovir, with or without 3TC.

They noted that most 3TC resistance in HBV has been associated with the combined L180M + M204I HBV reverse transcriptase mutations. More recently, the A194T mutation together with these 3TC-resistance mutations has been linked to tenofovir resistance.

The present retrospective, cross-sectional study included 44 HIV-HBV coinfected subjects who had received tenofovir for at least 3 months (mean duration 15 months). Of these, 28 had blood available samples while receiving tenofovir, and 24 also had available samples prior to starting tenofovir.

Results

• Of the pre-tenofovir samples, 15 of 24 (63%) were HBV DNA positive by PCR.

• 3TC-resistance mutations were identified in 7 of 15 (47%) of these viremic samples.

• Of the on-tenofovir samples, 6 of 28 (21%) tested positive for HBV DNA.

• 3TC-resistance mutations were detected in 4 of 6 (67%) of these viremic samples.

• Among the 6 subjects with detectable HBV DNA in their on-tenofovir samples, 4 also had detectable HBV DNA in their pre-tenofovir samples, and 2 did not have pre-tenofovir samples available.

• A unique polymerase mutation at K212M was identified in the on-tenofovir samples from 1 patient (3%).

• The previously identified tenofovir-resistance mutations at A194T + L180M + M204V were not observed in any of the on-tenofovir samples.

Conclusion

"Unique mutations associated with tenofovir resistance are rare in HIV-HBV coinfection," the researchers concluded. "One novel mutation was identified in HBV isolated from a patient during tenofovir treatment."

However, they added, "3TC-resistant mutations persist, and a fifth of patients are HBV PCR-positive despite the addition of tenofovir.

Alfred Hosp, Melbourne, Australia; Monash Univ, Melbourne, Australia; Ctr for Clin Res Excellence in Infectious Diseases, Univ of Melbourne, Australia; Victorian Infectious Diseases Reference Lab, North Melbourne, Australia; Burnet Inst, Melbourne, Australia; Victorian Infectious Diseases Svc, Melbourne, Australia.

Link to PDF of poster PDF

04/03/07

Reference
J Audsley, N Arrafin, L Yuen, and others. Surveillance of Hepatitis B Virus Mutations during Tenofovir Treatment in HIV/HBV-co-infected Individuals. 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, California. Abstract 942 (poster).











































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