Novel Deletion of HIV Type 1 Reverse Transcriptase Residue 69 Conferring Selective High-Level Resistance to Nevirapine

作者: Kazuo Suzuki , Gilbert R. Kaufmann , Motokazu Mukaide , Philip Cunningham , Claire Harris

DOI: 10.1089/088922201750461366

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

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