Adefovir dipivoxil (Hepsera)

Adefovir dipivoxil (Hepsera) is a licensed treatment for hepatitis B and a failed treatment for HIV.

Adefovir was previously called bis-POM PMEA and GS 840. It is made by Gilead Sciences. As a treatment for hepatitis B, it is known by the brand name Hepsera. As a treatment for HIV, adefovir was called Preveon.

The United States Food and Drug Administration (FDA) refused to approve adefovir as a treatment for HIV in 1999 due to the severity and frequency of kidney toxicity when dosed at 60 or 120mg. However, trials have found the 10mg dose of adefovir to be an effective and safe treatment for hepatitis B. Adefovir became an approved treatment for hepatitis B in the United States in August 2002 and in the European Union in March 2003.

Adefovir is a nucleotide reverse transcriptase inhibitor (NtRTI), but works against hepatitis B by blocking DNA polymerase, an enzyme crucial for the hepatitis B virus to reproduce in the body.


In test-tube studies adefovir has been shown to be active against a broad spectrum of viruses, including herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B virus and HIV-1 and -2. One study has found that adefovir also reduces CMV levels in semen.

In HIV-negative patients, adefovir is effective in reducing hepatitis B viral loads and preventing damage to the liver.1 It is also effective against 3TC (lamivudine, Epivir)-resistant hepatitis B and improves liver function in people with ‘pre-core mutant chronic hepatitis B virus’, which is associated with rapid progression to liver disease.2

It is also effective in HIV-co-infected patients. A multi-centre, open label study, 35 people co-infected with HIV and HBV, who had undetectable HIV viral load and proven 3TC-resistant hepatitis B, were given 10mg adefovir once daily, in addition to their existing anti-HIV treatment regimen. After 48 weeks of treatment, significant decreases in HBV viral load were observed across the study group, with an average fall in viral load of 4.0 log10. There were no changes in the patients’ HIV viral loads or CD4 cell counts.3 These findings have now been extended to three years, with sustained suppression of hepatitis B.4

The efficacy of adefovir is enhanced when it is combined with nucleoside reverse transcriptase inhibitors (NRTIs), including 3TC, entecavir, FTC (emtricitabine, Emtriva) and telbivudine, or the NtRTI tenofovir (Viread).5 There is no interaction between adefovir and tenofovir in terms of blood concentrations or clearance through the kidneys.6

Adefovir at the dose studied for its anti-HIV properties can reduce the levels of saquinavir in patients taking the discontinued soft-gel formulation of the drug in combination with low-dose ritonavir (Norvir).7 8 It is not known whether this also occurs with the 10mg dose used for treating hepatitis B, or with the hard-gel formulation of saquinavir (Invirase).


When dosed at 60 or 120mg daily, adefovir commonly causes liver or kidney abnormalities. In one study, around 20% of the people taking 120mg adefovir daily developed kidney problems during twelve months of adefovir treatment. The 60mg dose was not as toxic but still caused serious kidney dysfunction in 3% of 1500 people receiving adefovir as a treatment for HIV through an expanded access scheme.9

The safety problems observed at the dose used in HIV infection have not been a widespread problem at the 10mg dose used for hepatitis B treatment, although two cases of elevated creatinine have been reported at this dose in patients also receiving indinavir (Crixivan) treatment, which is known to cause kidney toxicity. Placebo-controlled studies conducted over 12 months using the 10mg dosage indicate that adefovir is safe.10 Few other side-effects have been reported to date.


There are concerns that adefovir monotherapy for hepatitis B may lead to drug resistance. However, although mutations do occur in the presence of adefovir, no pathway to drug resistance has been identified.11

Another concern is that low dose adefovir used for hepatitis B treatment in HIV co-infected patients may select for HIV mutations. This may lead to cross-resistance to anti-HIV drugs such as tenofovir, AZT (zidovudine, Retrovir), d4T (stavudine, Zerit), abacavir (Ziagen), ddI (didanosine, Videx / VidexEC) and 3TC. Studies monitoring the onset of mutations in the reverse transcriptase gene during treatment with adefovir has shown that the adefovir-associated resistance mutations K65R and K70E did not arise after up to 12 months of adefovir treatment at 10mg daily, suggesting that this is a minor risk.12 13


  1. Hadziyannis SJ et al. Long-term therapy with adefovir dipivoxil for HbeAg-negative chronic hepatitis B. N Engl J Med 352: 2673-2681, 2005
  2. Westland CE et al. Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients. J Viral Hepat 12: 67-73, 2005
  3. Benhamou Y et al. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet 358: 718-723, 2001
  4. Benhamou Y et al. Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1. J Hepatol 44: 62-67, 2006
  5. Delaney WE et al. Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro. Antimicrob Agents Chemother 48: 3702-3710, 2004
  6. Kearney BP et al. Lack of systemic or renal drug interactions of tenofovir DF with adefovir dipivoxil or ribavirin. 15th International AIDS Conference, Bangkok, abstract TuPeB4628, 2004
  7. Brundage RC et al. Quantitation of sex differences and drug interactions: pharmacologic studies of saquinavir (SQV) in ACTG 359. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 779, 2002
  8. Fletcher CV et al. Competing drug-drug interactions among multidrug antiretroviral regimens used in the treatment of HIV-infected subjects: ACTG 884. AIDS 14: 2495-2501, 2000
  9. Nuessle SJ et al. The Preveon Expanded Access Program: safety of adefovir dipivoxil (ADV) in antiretroviral treatment experienced patients with advanced HIV disease. Sixth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 379, 1999
  10. Izzedine H et al. Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies. Kidney Int 66: 1153-1158, 2004
  11. Yang H et al. Resistance surveillance in chronic hepatitis B patients treated with adefovir dipivoxil for up to 60 weeks. Hepatology 36: 464-473, 2002
  12. Delaugerre C et al. Human immunodeficiency virus (HIV) type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine. Antimicrob Agents Chemother 46: 1586-1588, 2002
  13. Sheldon JA et al. Risk of selecting K65R in antiretroviral-naive HIV-infected individuals with chronic hepatitis B treated with adefovir. AIDS 19: 2036-2038, 2005

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

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