Open AccessCoresistance to Zidovudine and Foscarnet Is Associated with Multiple Mutations in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase
Author(s) -
Gilda Tachedjian,
Martyn A. French,
John Mills
Publication year - 1998
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.42.11.3038
Subject(s) - zidovudine , foscarnet , reverse transcriptase , virology , reverse transcriptase inhibitor , human immunodeficiency virus (hiv) , didanosine , lentivirus , nucleoside reverse transcriptase inhibitor , biology , virus , rna directed dna polymerase , sida , viral disease , polymerase chain reaction , antiretroviral therapy , genetics , viral load , gene , herpesviridae
Human immunodeficiency virus type 1 (HIV-1) isolates obtained from a patient with AIDS were assessed for coresistance to foscarnet and zidovudine. An HIV-1 strain (AP20) coresistant to foscarnet and zidovudine was isolated after 20 months of continuous combination therapy. The reverse transcriptase (RT) gene of AP20 had 41 substitutions which were different from the HXB2-D sequence and 9 that were different from the sequence of its foscarnet-sensitive, zidovudine-resistant progenitor virus (AP6). Six of these mutations were nonpolymorphic (T39A, V108I, K166R, K219R, K223Q, and L228R). Both strains had the conventional mutations mediating zidovudine resistance. In vivo selection may result in HIV-1 strains that are coresistant to foscarnet and zidovudine, but coresistance appears to require a complex evolutionary path and multiple RT mutations.
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