Development of resistance and perspectives for future therapies against hepatitis B infections: lessons to be learned from HIV

[Guest guest]

Infection 1999;27 Suppl 2:S45-51

Development of resistance and perspectives for future therapies against

hepatitis B infections: lessons to be learned from HIV.

Deres K, Rubsamen-Waigmann H

Dept. of Virology, Geschaftsbereich Pharma, Bayer AG, Wuppertal, Germany.

[Medline record in process]

Several first-generation nucleoside analogues have been tested against

chronic hepatitis B virus (HBV) infection, but trials were unsuccessful or

accompanied by toxicity. Recently, oral second-generation nucleoside

analogues have been developed that have potent activity against HBV. The

best-studied compound so far is lamivudine ((-)2'-deoxy-3'-thiacytidine;

3TC). Lamivudine is an inhibitor of reverse transcriptase (RT) activity and

is in clinical use in human immunodeficiency virus (HIV)-infected

individuals. As several studies on the use of lamivudine for hepatitis B

show, the development of resistance in the viral polymerase under lamivudine

treatment, however, causes a significant clinical problem. All other drugs

in advanced clinical development for HBV are nucleosides; cross-resistance

is therefore expected in most cases. The history of HIV treatment

demonstrates that new classes of drugs, the protease inhibitors and

non-nucleosidic inhibitors of RT, allowed for a longer-term clinical benefit

when used in combination with nucleoside analogues. The development of

non-nucleosidic compounds with different modes of action therefore appears

very important for the treatment of chronic hepatitis B as well.

PMID: 10885829, UI: 20340377

[Guest guest]

Infection 1999;27 Suppl 2:S45-51

Development of resistance and perspectives for future therapies against

hepatitis B infections: lessons to be learned from HIV.

Deres K, Rubsamen-Waigmann H

Dept. of Virology, Geschaftsbereich Pharma, Bayer AG, Wuppertal, Germany.

[Medline record in process]

Several first-generation nucleoside analogues have been tested against

chronic hepatitis B virus (HBV) infection, but trials were unsuccessful or

accompanied by toxicity. Recently, oral second-generation nucleoside

analogues have been developed that have potent activity against HBV. The

best-studied compound so far is lamivudine ((-)2'-deoxy-3'-thiacytidine;

3TC). Lamivudine is an inhibitor of reverse transcriptase (RT) activity and

is in clinical use in human immunodeficiency virus (HIV)-infected

individuals. As several studies on the use of lamivudine for hepatitis B

show, the development of resistance in the viral polymerase under lamivudine

treatment, however, causes a significant clinical problem. All other drugs

in advanced clinical development for HBV are nucleosides; cross-resistance

is therefore expected in most cases. The history of HIV treatment

demonstrates that new classes of drugs, the protease inhibitors and

non-nucleosidic inhibitors of RT, allowed for a longer-term clinical benefit

when used in combination with nucleoside analogues. The development of

non-nucleosidic compounds with different modes of action therefore appears

very important for the treatment of chronic hepatitis B as well.

PMID: 10885829, UI: 20340377