Experimental treatments

More than 20 agents are being tested as treatments for HBV. Drugs furthest along the development pipeline are Gilead Sciences' FTC and tenofovir, which have both already been approved for HIV, Pharmasset's clevudine (L-FMAU), Idenix's telbivudine (LdT), and Novartis' famciclovir (Famvir). Famciclovir is already approved for herpes simplex virus.

FTC monotherapy has shown promising results in HIV-negative people with HBV, with 64% of patients taking the 200mg daily dose achieving undetectable HBV at 36 weeks.1 It also has shown potent activity against both HBV and HIV in co-infected individuals.2

Studies have shown that tenofovir is as or more effective against HBV than adefovir, although HBV can develop resistance to tenofovir.3 4 Further, as suggested above, in the context of HIV co-infection, the use of tenofovir may be a more attractive option than adefovir because tenofovir has activity against both HIV and HBV.

Two small studies of tenofovir in co-infected people found substantial reductions in hepatitis B virus DNA of between 3.4 and 4.6 log10.5 6 In an open-label study of tenofovir in HIV/hepatitis B co-infected patients, five people seroconverted to HBeAg-negative, indicating hepatitis B viral clearance.7  In this study, previous exposure to 3TC did not affect response to tenofovir. Another controlled study found that tenofovir is at least as effective as adefovir in controlling HBV in HIV/HBV co-infected patients.8

How co-infected people can get maximal benefit from tenofovir is yet to be established. One consideration is that tenofovir is a useful agent for salvage therapy in HIV treatment, because it is active against virus with a wide range of nucleoside reverse transcriptase inhibitor mutations, including 3TC resistance, so it may not be attractive to use this agent as first-line therapy in co-infected patients, in order to save it if needed later. In addition, as is the case with 3TC, discontinuation of tenofovir can cause severe hepatitis flare-ups.

Other drugs in the pipeline include: valtorcitabine (val-LdC); amdoxovir (DAPD); lobucavir; LB80380 (ANA380); pradefovir (a pro-drug of adefovir, formerly called remefovir); elvucitabine; penciclovir; racivir; NOV-205; L-3'-FD4C (Pentacept); UT 231-B; DXG; thymosin (Zadaxin); and various therapeutic vaccine candidates.6

References

  1. Rousseau F et al. Emtricitabine (FTC): HBV DNA viral load assessments over 36 weeks in patients with chronic HBV infection. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 559, 2001
  2. Harris J et al. Emtricitabine therapy for hepatitis infection in HIV-1 patients co-infected with hepatitis B: antiviral response and genotypic findings in antiretroviral treatment naïve patients. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 836, 2004
  3. Sheldon J et al. Genotypic changes in HBV-DNA of HBV/HIV co-infected patients after long-term exposure to tenofovir. 44th Interscience Conference of Antimicrobial Agents and Chemotherapy, Washington, DC, abstract V-1154, 2004
  4. van Bö­­mmel F et al. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology 40: 1421-1425, 2004
  5. Bochet M et al Tenofovir disoproxil fumarate suppresses lamivudine resistant HBV replication in patients co-infected with HIV/HBV Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract P 675-M, 2002
  6. Cooper D et al. Anti-HBV activity of tenofovir disoproxil fumarate (TDF) in lamivudine (LAM) experienced HIV/HBV co-infected. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 124, 2002
  7. Nelson M et al. An open-label study of tenofovir in HIV-1 and hepatitis B virus co-infected individuals. AIDS 17: F7-F10, 2003
  8. Peters M et al. Tenofovir disoproxil fumarate is not inferior to adefovir dipivoxil for the treatment of hepatitis B virus in subjects who are coinfected with HIV: results of ACTG A5127. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 124, 2005
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