The pharmacology of zidovudine

Abstract

Zidovudine (3′ azido-3′-deoxythymidine, ZDV, AZT, Retrovir), first synthesized for use as a chemotherapeutic agent, currently is approved by the Food and Drug Administration (FDA) for therapy of human immunodeficiency virus (HIV) infection. Other FDA-approved antiretroviral agents include dideoxyinoside, dideoxycytidine, and stavudine. Zidovudine, a thymidine analogue, inhibits replication of human immunodeficiency virus. Although initially very effective in slowing the progression of acquired immunodeficiency syndrome, the benefits of zidovudine are transient, and the patient eventually succumbs to the opportunistic infections characteristic of AIDS. Investigations in patients with advanced HIV have demonstrated that treatment with zidovudine results in prolonged survival, decreased frequency of opportunistic infections, improvement in encephalopathy (in both adults and children), and reduction of adult T-cell leukemia (in combination with interferon-α). Importantly, zidovudine crosses the placenta in a concentration-dependent manner, and a significant reduction in vertical transmission of HIV to the fetus has been demonstrated clearly. Adverse reactions are well described and are related to dose and stage of disease. Most notably, anemia and neutropenia complicate therapy. Anemia most commonly presents within the first 3 months of drug therapy, whereas neutropenia may occur early or late. More-over, anemia may also occur in the newborn when zidovudine is used to prevent vertical transmission. Fortunately, most complications are manageable by recognition and close monitoring by the physician.