Adefovir for hep B: not an HIV resistance risk

Francois Houyez
Estimated reading time 2 minutes
This article is more than 24 years old.

Adefovir dipivoxil (Preveon) is an antiviral product active against both HBV and HIV. Its toxicity limits its use against HIV. Preveon was refused a license for the treatment of HIV infection in the United States because the effective dose (60 mg daily) exposes patients to a high risk of renal toxicity with only a modest impact on HIV viral load.

Nevertheless, it is a potent drug against wild type and lamivudine resistant hepatitis B virus, and is currently in phase III of its clinical development, but at a much lower dose: 10 mg daily. The use of 10 mg adefovir daily in HIV/HBV co-infected patients has been explored by virologists at the Pitié Salpétrière University Hospital, Paris (C. Delaugerre, AG. Marcelin, V. Calvez), and was reported at the Fifth International Workshop on HIV Drug Resistance last week in Arizona. One concern is that low dose adefovir treatment may select drug resistant mutants which are cross-resistant to anti-HIV drugs such as AZT, d4T, abacavir, ddI and 3TC.

Among patients with a detectable HIV viral load above 400 copies/ml, it was possible to monitor the onset of mutations in the reverse transcriptase gene during treatment, over a 12 months period of time.

Glossary

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

toxicity

Side-effects.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

detectable viral load

When viral load is detectable, this indicates that HIV is replicating in the body. If the person is taking HIV treatment but their viral load is detectable, the treatment is not working properly. There may still be a risk of HIV transmission to sexual partners.

Sequences from 13 patients at day 0, month 3, month 6 and month 12 were compared to a reference sequence (HXB2).

At baseline, all patients harboured the M184V mutation. All patients received at least one thymidine analogue against HIV at the same time as adefovir.

Neither the adefovir associated resistance mutations K65R nor K70E, nor any other specific resistance pattern, was observed after 12 months of adefovir treatment at 10 mg daily. Thus, low adefovir doses used to treat the HBV infection do not increase the risk of acquiring mutations conferring resistance to other anti-HIV products.

Reference

Marcelin AG et al. HIV-1 reverse transcriptase resistance mutations profile in HBV-HIV-1 co-infected patients treated by a combination of adefovir dipivoxil 10mg once daily and lamivudine for their HBV infection. Fifth International Workshop on HIV Drug Resistance and Treatment Strategies, Scottsdale, abstract 112, 2001.

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