824 Long-term Tenofovir Treatment of Lamivudine-resistant Chronic Hepatitis B in HIV Co-infected Patients A. G. Marcelin*, R. Tubiana, Y. Benhamou, C. Katlama, V. Calvez, V. Thibault Paris, France
Background: YMDD mutations in the hepatitis B virus (HBV) DNA polymerase have been observed with lamivudine (LAM) therapy and are associated with progressive liver disease and clinical deterioration. The incidence of YMDD mutations in patients (pts) co-infected with HIV may be as high as 91% at 4 yrs. Tenofovir disoproxil fumarate (TDF) is active against HIV but possesses also in vitro activity against both wild-type and LAM-R HBV mutant. Therefore, TDF might be an interesting alternative for HIV-infected pts with chronic hepatitis B resistant to lamivudine. We have examined the efficacy of TDF 300 mg once daily in HIV/HBV co-infected pts with lamivudine resistant HBV infection.
Methods: Ten (10) HIV/HBV co-infected pts (mean age 44 yrs) treated with LAM as part of their antiretroviral therapy had TDF added to their treatment. Monitoring includes HIV and HBV viral load, transaminases determination, and CD4 cell count on a monthly basis for the first 3 months (mos) and every 3 mos thereafter. HIV and HBV genotyping was performed prior to TDF initiation, 3 mos later, and whenever an increase in viral load was noted.
Results:At baseline, all but 1 pt were positive for HBe antigen; 9 pts had HBV lamivudine resistant mutations (rtM204V/I and L180M); 5 pts had undetectable HIV viral load (< 200 copies/mL) and the mean viral load for the remaining was 3.49 ±0.45 (mean ±SE) Log copies/mL. Twelve (12) mos after TDF introduction, the mean reduction of HBV viral load was 4.55 ±1.21 Log (mean ±SE) and 3 pts had less than 200 copies/mL; no pt experienced HBeAg loss or seroconversion. Transaminase levels slightly improved during treatment with a mean drop of 25 IU/L. No significant change in HIV viral load was detected during treatment and 6 pts were below 200 copies/mL at mo 12 follow-up. At 3 mos after treatment initiation, genotyping analysis did not reveal the emergence of HBV specific mutation or HIV TDF associated mutation at reverse-transcriptase codon K65R. Treatment was well tolerated and was not associated with any clinical adverse event.
Conclusions: Our 12-mo temporary analysis demonstrates that TDF, when added to an effective antiretroviral treatment, is a potential alternative therapeutic option against LAM-R HBV. Noteworthy, TDF treatment was not associated with the emergence of HIV or HBV specific resistance mutations. The ongoing dramatic HBV load reduction confirms in vivo the good efficacy of TDF on HBV YMDD mutants.