Long-term foscarnet therapy not associated with the development of foscarnet-resistant human immunodeficiency virus type 1 in an acquired immunodeficiency syndrome patient

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Abstract
Sequential human-immunodeficiency virus type 1 (HIV-1) isolates from an acquired immunodeficiency syndrome (AIDS) patient on long-term foscarnet and zidovudine therapy were examined for the emergence of foscarnet resistance. One isolate obtained before therapy, and three post-foscarnet therapy HIV isolates had similar foscarnet sensitivity profiles, despite the emergence of foscarnet-resistant herpes simplex virus type 2 (HSV-2) during the period of therapy. Virion reverse transcriptases from these isolates were also equally inhibited by foscarnet. In contrast, sequential HIV isolates taken pre- and postzidovudine therapy showed a gradual increase in IC50 to this drug. In this patient, long-term foscarnet and zidovudine therapy selected foscarnet-resistant HSV and zidovudine-resistant HIV; in contrast, HIV remained susceptible to foscarnet. Concurrent administration of other anti-HIV drugs (zidovudine and interferon-alpha) may have hindered the development of foscarnet resistant HIV-1 in vivo.

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