Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine.

Abstract:

:A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapine (NVP). Longitudinal analysis of samples revealed that this deletion emerged upon reinitiation DDI/D4T therapy following a toxicity-induced short discontinuation of all antiretrovirals. Analysis of the resistance phenotype showed a greater than 62-fold increase of the IC50 of NVP, but no significant change in sensitivity to other single nonnucleoside reverse transcriptase inhibitors (NNRTIs). The mutated virus showed only a moderately reduced sensitivity to DDI (6.7-fold) and D4T (4.8 fold). In a subsequent sample 3 months later additional RT mutations were found, including A62V, Y188L, and Q151M, conferring high-level cross-resistance to multiple nucleoside analogs. Our findings provide evidence that the deletion of RT residue 69 selectively confers high-level NVP resistance.

authors

Suzuki K,Kaufmann GR,Mukaide M,Cunningham P,Harris C,Leas L,Kondo M,Imai M,Pett SL,Finlayson R,Zaunders J,Kelleher A,Cooper DA

doi

10.1089/088922201750461366

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

1293-6

issue

13

eissn

0889-2229

issn

1931-8405

journal_volume

17

pub_type

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