Zalcitabine is an analogue of the
nucleoside deoxycytidine which, when intracellularly converted to an active
triphosphate metabolite, inhibits replication of human immunodeficiency virus (HIV).
Zalcitabine is thought to act in the early phase of HIV replication by inhibiting
reverse transcriptase and terminating the
viral DNA chain. In vitro,
zalcitabine is one of the more effective
nucleoside analogues currently in clinical use for
HIV infection, with 0.5 mumol/L concentrations completely inhibiting HIV replication in human T lymphocyte cell lines. In clinical trials, p24
antigen levels decreased and CD4 cell counts increased in patients with
acquired immunodeficiency syndrome (
AIDS) receiving
zalcitabine > or = 0.03 mg/kg/day as monotherapy. Dose-dependent adverse effects that include
peripheral neuropathy,
stomatitis and
rash, restrict long term use at higher dosages, and it is unclear whether
zalcitabine monotherapy is as effective as
zidovudine in extending survival in HIV-infected patients. Alternating or concomitant
therapy with
zalcitabine and
zidovudine provides effective inhibition of viral replication and
disease progression (as measured by improvements in CD4 cell counts) with lower and less toxic dosage regimens. At present, therefore,
zalcitabine has a place in
AIDS therapy both in combination with
zidovudine, and as monotherapy for patients unable to tolerate
zidovudine.