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Open Access Research article

Impact of Y181C and/or H221Y mutation patterns of HIV-1 reverse transcriptase on phenotypic resistance to available non-nucleoside and nucleoside inhibitors in China

Wei Guo, Hanping Li, Daomin Zhuang, Liyan Jiao, Siyang Liu, Lin Li, Yongjian Liu, Tao Gui, Lei Jia and Jingyun Li*

Author Affiliations

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Fengtai District, Beijing 100071, China

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BMC Infectious Diseases 2014, 14:237  doi:10.1186/1471-2334-14-237

Published: 5 May 2014

Abstract

Background

The aim of this study was to investigate the role of K101Q, Y181C and H221Y emerging in HIV-1 reverse transcriptase with different mutations patterns in phenotypic susceptibility to currently available NNRTIs (nevirapine NVP, efavirenz EFV) and NRTIs (zidovudine AZT, lamivudine 3TC, stavudine d4T) in China.

Methods

Phenotype testing of currently available NNRTIs (NVP, EFV) and NRTIs (AZT, 3TC, d4T) was performed on TZM-b1 cells using recombined virus strains. P ≤ 0.05 was defined significant considering the change of 50% inhibitory drug concentration (IC50) compared with the reference, while P ≤ 0.01 was considered to be statistically significant considering multiple comparisons.

Results

Triple-mutation K101Q/Y181C/H221Y and double-mutation K101Q/Y181C resulted in significant increase in NVP resistance (1253.9-fold and 986.4-fold), while only K101Q/Y181C/H221Y brought a 5.00-fold significant increase in EFV resistance. Remarkably, K101Q/H221Y was hypersusceptible to EFV (FC = 0.04), but was significantly resistant to the three NRTIs. Then, the interaction analysis suggested the interaction was not significant to NVP (F = 0.77, P = 0.4061) but significant to EFV and other three NRTIs.

Conclusion

Copresence of mutations reported to be associated with NNRTIs confers significant increase to NVP resistance. Interestingly, some may increase the susceptibility to EFV. Certainly, the double mutation (K101Q/H221Y) also changes the susceptibility of viruses to NRTIs. Interaction between two different sites makes resistance more complex.

Keywords:
Nucleoside reverse transcriptase inhibitors (NRTIs); Non-nucleoside reverse transcriptase inhibitors (NNRTIs); HIV-1 resistance mutation; 50% inhibitory drug concentration