Zidovudine (AZT) Monotherapy Selects for the A360V Mutation in the Connection Domain of HIV-1 Reverse Transcriptase

@inproceedings{Brehm2012ZidovudineM,
  title={Zidovudine (AZT) Monotherapy Selects for the A360V Mutation in the Connection Domain of HIV-1 Reverse Transcriptase},
  author={Jessica H. Brehm and Yanille Scott and Dianna Koontz and Steven C. Perry and Scott M. Hammer and David K. Katzenstein and John W Mellors and Nicolas Sluis-Cremer},
  booktitle={PloS one},
  year={2012}
}
BACKGROUND We previously demonstrated in vitro that zidovudine (AZT) selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V, Q509L or other mutations in the C-terminal domains of HIV-1 RT… CONTINUE READING

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Full - length RT sequences in plasma obtained pre- and post - therapy were compared in 23 participants who received AZT monotherapy from the AIDS Clinical Trials Group study 175 .
Full - length RT sequences in plasma obtained pre- and post - therapy were compared in 23 participants who received AZT monotherapy from the AIDS Clinical Trials Group study 175 .
HIV InfectionsMay be treated byZidovudine
The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V , Q509L or other mutations in the C - terminal domains of HIV-1 RT .
Mutations significantly associated with AZT monotherapy included K70R ( p = 0.003 ) and T215Y ( p = 0.013 ) in the polymerase domain of HIV-1 RT , and A360V ( p = 0.041 ) in the connection domain of HIV-1 RT .
The A360V mutation in the connection domain of RT was selected in HIV - infected individuals that received AZT monotherapy and contributed to AZT resistance .
The A360V mutation in the connection domain of RT was selected in HIV - infected individuals that received AZT monotherapy and contributed to AZT resistance .
Mutations significantly associated with AZT monotherapy included K70R ( p = 0.003 ) and T215Y ( p = 0.013 ) in the polymerase domain of HIV-1 RT , and A360V ( p = 0.041 ) in the connection domain of HIV-1 RT .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
HIV-1 drug susceptibility assays demonstrated that A360V , either alone or in combination with thymidine analog mutations , decreased AZT susceptibility in recombinant viruses containing participant - derived full - length RT sequences or site - directed mutant RT .
Full - length RT sequences in plasma obtained pre- and post - therapy were compared in 23 participants who received AZT monotherapy from the AIDS Clinical Trials Group study 175 .
Mutations significantly associated with AZT monotherapy included K70R ( p = 0.003 ) and T215Y ( p = 0.013 ) in the polymerase domain of HIV-1 RT , and A360V ( p = 0.041 ) in the connection domain of HIV-1 RT .
Mutations significantly associated with AZT monotherapy included K70R ( p = 0.003 ) and T215Y ( p = 0.013 ) in the polymerase domain of HIV-1 RT , and A360V ( p = 0.041 ) in the connection domain of HIV-1 RT .
The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V , Q509L or other mutations in the C - terminal domains of HIV-1 RT .
The A360V mutation in the connection domain of RT was selected in HIV - infected individuals that received AZT monotherapy and contributed to AZT resistance .
The A360V mutation in the connection domain of RT was selected in HIV - infected individuals that received AZT monotherapy and contributed to AZT resistance .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
HIV-1 drug susceptibility assays demonstrated that A360V , either alone or in combination with thymidine analog mutations , decreased AZT susceptibility in recombinant viruses containing participant - derived full - length RT sequences or site - directed mutant RT .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
We previously demonstrated in vitro that zidovudine ( AZT ) selects for A371V in the connection domain and Q509L in ribonuclease H ( RNase H ) domain of HIV-1 reverse transcriptase ( RT ) which , together with the thymidine analog mutations D67N , K70R and T215F , confer greater than 100-fold AZT resistance .
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