Lamivudine in the Management of Adults with Human Immunodeficiency Virus Type 1 Infection

Abstract

Lamivudine is a nucleoside analogue reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1), HIV-2 and hepatitis B virus which demonstrates in vitro activity with a high therapeutic index in a range of T lymphocyte and haematopoietic precursor cell lines. It is synergistic in vitro with a range of other antiretrovirals including other nucleoside analogues, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, in two- and three-way combinations and is active against virus resistant to zidovudine and most other antiretrovirals. It exhibits excellent oral bioavailability and penetrates the CSF. In clinical use, lamivudine exhibits limited antiretroviral activity as a monotherapy, but in two-and three-drug combinations with other antiretrovirals it provides potent antiretroviral activity and significantly delays clinical events. Adverse events appear infrequent and are generally mild and self-limiting. Resistance to lamivudine develops rapidly in vitro and in vivo but may delay the development of zidovudine resistance. Dual zidovudine-lamivudine resistance is well documented both in vitro and in vivo although the mutation at codon 184 of reverse transcriptase characteristic of lamivudine resistance may, in some cases, transiently ‘reverse’ zidovudine resistance mediated through codons 215 and 41. Owing to concerns regarding selection of virus with cross-resistance to other nucleoside analogues (ddl, ddC and possibly abacavir), whether to use lamivudine in initial or second-line regimens is currently under debate.