Long-term foscarnet therapy not associated with the development of foscarnet-resistant human immunodeficiency virus type 1 in an acquired immunodeficiency syndrome patient.
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.
Tachedjian
G
G
Macfarlane Burnet Centre for Medical Research, Fairfield Hospital, Victoria, Australia.
Hoy
J
J
McGavin
K
K
Birch
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics*; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000235:genetics; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use
D017245:Foscarnet; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase