Drug Evaluations: Drug Evaluation Anti-infectives: Activity and role of lamivudine in the treatment of adults with human immunodeficiency virus type 1 infection: A review

Abstract

Lamivudine is a nucleoside analogue reverse transcriptase inhibitor of 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 zidovudine and a range of other antiretrovirals, including the proteinase inhibitor saquinavir, in two- and three-way combinations and is active against zidovudine-resistant virus. Whilst it exhibits excellent oral bioavailability, the CSF/plasma ratio of lamivudine is lower than those reported with other licensed antiretrovirals. In clinical use, lamivudine exhibits limited antiretroviral activity as a monotherapy, but in combination with zidovudine results in more substantial and durable responses in immunological and virological markers than zidovudine alone. Clinical end-point data from lamivudine trials are now awaited. Clinical trials in combination with zidovudine in patients both naive to and experienced with prior antiretroviral therapy and CD4 cell count between 100 and 500/mm3 suggest that addition of lamivudine 150 mg bid results in a similar frequency of adverse events to that observed with zidovudine alone. Resistance to lamivudine develops rapidly in vitro and in vivo but may delay the development of zidovudine resistance. The mutation at codon 184 of reverse transcriptase characteristic of lamivudine resistance may, in some cases, antagonise or ‘reverse’ zidovudine resistance mediated through codons 215 and 41; however, dual zidovudine-lami-vudine resistance has been reported both in vitro and in vivo. Lamivudine has a clinical role as a combination agent both as initial therapy and in patients with prior zidovudine experience.