In vitro selection and characterization of human immunodeficiency virus type 1 resistant to Zidovudine and tenofovir.
In this study, we undertook to generate HIV-1 resistance to PMPA by in vitro passage and to characterize the cross-resistance patterns and RT mutations in the generated resistant virus. The HIV-1 A102-resistant to AZT was serially passaged for 4 months in the presence of increasing concentrations of PMPA up to maximum of 40 microM on the fresh MT-2 cells. After 25 passages, HIV-1 developed decreased sensitivity to PMPA after long-term in vitro exposure. Selected HIV-1 mutants were characterized by decreased susceptibility to PMPA (4-fold). This decrease could be related to PMPA resistant caused by an amino acid change associated with a V148M substitution. From these results, additional studies will be needed to determine whether a similar mutation in HIV RT develops in patients receiving PMPA or its orally bioavailable prodrug, tenofovir dipivoxil fumarate.
Park
S-S
SS
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Hong
S-K
SK
Lee
S-G
SG
Yoon
J-S
JS
Yoo
W-C
WC
Paik
S-Y
SY
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D002461:Cell Line, Transformed; D024882:Drug Resistance, Viral / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D000068698:Tenofovir; D015215:Zidovudine / Q000494:pharmacology*
D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000068698:Tenofovir; D054303:HIV Reverse Transcriptase; D000225:Adenine