Chapnick and colleagues have described another case of zidovudine-induced hepatitis, emphasizing this rare but possible side effect. In our review [1], we also cite four cases of severe liver dysfunction that occurred in patients in AIDS Clinical Trial Groups (ACTG) studies who were receiving zidovudine (notification from Division of AIDS, National Institute of Allergy and Infectious Diseases, to ACTG investigators, 14 November 1991). These patients were all women in an early stage of HIV infection and had not developed the acquired immunodeficiency syndrome (AIDS). Three of these patients died of liver failure; fatty liver changes were noted on biopsy or autopsy. Although a precise cause and effect was not established, we concur that physicians treating patients with zidovudine should be aware of its possible hepatotoxicity.

Stricker and Elswood have underscored the in-vitro finding that zidovudine inhibits the growth and the mitogenic response of peripheral blood mononuclear cells. The relevance of these findings to the in-vivo situation is unclear but they may be important as a possible mechanism in the eventual decline of CD4⁺ cell counts in patients on prolonged zidovudine therapy. Patients with HIV-associated encephalopathy have been shown to respond to zidovudine with improvement in virologic markers (that is, negative HIV cultures and decreased p24 antigen) in the cerebrospinal fluid [2, 3]. Thus, the antiviral effects of zidovudine may be more important in this condition than any direct immunomodulatory effect. The pathogeneses of HIV-associated thrombocytopenia and psoriasis are not fully known. The speculation that an anti-inflammatory effect may account for the therapeutic response to zidovudine in patients with these conditions is intriguing, but further research is needed.