Failure of Zidovudine Prophylaxis after Exposure to HIV-1

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Abstract
In their case report of a failure of zidovudine prophylaxis after exposure to human immunodeficiency virus type 1 (HIV-1) (May 10 issue),1 Lange and colleagues fail to mention what is perhaps the most likely explanation for the observed clinical failure: that zidovudine may lack efficacy as a prophylactic agent regardless of the dose or duration of therapy or the size or type of inoculum. Zidovudine has no virucidal activity against HIV-1, and as Lange et al. note, it may be ineffective in blocking cell-to-cell transmission or in completely inhibiting reverse transcriptase. These deficiencies may allow the establishment of latent infection, with integration of the viral genome into the host chromosomes. This has been observed in the studies of zidovudine prophylaxis in animal retrovirus models that specifically screened for the establishment of viral infection with sensitive methods such as the polymerase chain reaction.2 , 3 In these studies, early administration of zidovudine after exposure (or even before exposure) modified the initial clinical, virologic, and immunologic manifestations of the infection but failed to prevent chronic infection.

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