Evaluation of a Novel In-house HIV-1 Genotype Drug Resistance Assay using Clinical Samples in China

Page: [32 - 41] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic.

Objective: The study aims to establish a novel in-house assay with high efficiency, named AP inhouse method, that would be suitable for HIV-1 drug resistance detection in China.

Methods: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system.

Results: Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_ BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system.

Conclusion: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversified HIV-1 subtypes in China.

Keywords: HIV-1, anti-retroviral treatment, genotype, drug resistance mutation, protease inhibitor, nucleoside reverse transcriptase inhibitors, non-Nucleoside reverse transcriptase inhibitors.

Graphical Abstract

[1]
Bandera A, Gori A, Clerici M, Sironi M. Phylogenies in ART: HIV reservoirs, HIV latency and drug resistance. Curr Opin Pharmacol 2019; 48: 24-32.
[http://dx.doi.org/10.1016/j.coph.2019.03.003] [PMID: 31029861]
[2]
Churchill MJ, Deeks SG, Margolis DM, Siliciano RF, Swanstrom R. HIV reservoirs: what, where and how to target them. Nat Rev Microbiol 2016; 14(1): 55-60.
[http://dx.doi.org/10.1038/nrmicro.2015.5] [PMID: 26616417]
[3]
Kumi Smith M, Jewell BL, Hallett TB, Cohen MS. Treatment of HIV for the prevention of transmission in discordant couples and at the population level. Adv Exp Med Biol 2018; 1075: 125-62.
[http://dx.doi.org/10.1007/978-981-13-0484-2_6] [PMID: 30030792]
[4]
Lu DY, Wu HY, Yarla NS, Xu B, Ding J, Lu TR. HAART in HIV/AIDS Treatments: Future Trends. Infect Disord Drug Targets 2018; 18(1): 15-22.
[http://dx.doi.org/10.2174/1871526517666170505122800] [PMID: 28474549]
[5]
Pace M, Frater J. A cure for HIV: is it in sight? Expert Rev Anti Infect Ther 2014; 12(7): 783-91.
[http://dx.doi.org/10.1586/14787210.2014.910112] [PMID: 24745361]
[6]
Cao W, Hsieh E, Li T. Optimizing treatment for adults with HIV/AIDS in China: Successes over two decades and remaining challenges. Curr HIV/AIDS Rep 2020; 17(1): 26-34.
[http://dx.doi.org/10.1007/s11904-019-00478-x] [PMID: 31939111]
[7]
Peng Z, Wang S, Xu B, Wang W. Barriers and enablers of the prevention of mother-to-child transmission of HIV/AIDS program in China: A ystematic review and policy implications. Int J Infec Dis 2017; 55: 72-80.
[8]
Wen Y, Bar KJ, Li JZ. Lessons learned from HIV antiretroviral treatment interruption trials. Curr Opin HIV AIDS 2018; 13(5): 416-21.
[http://dx.doi.org/10.1097/COH.0000000000000484] [PMID: 29878912]
[9]
Zhao S, Feng Y, Hu J, et al. Prevalence of Transmitted HIV drug resistance in antiretroviral treatment naïve newly diagnosed individuals in China. Sci Rep 2018; 8(1): 12273.
[http://dx.doi.org/10.1038/s41598-018-29202-2] [PMID: 30115986]
[10]
Zhao Y, Han MJ, Gan XM, Ma Y, Zhao DC. Characteristics and viral suppression among people living with HIV from the National Free Antiretroviral Therapy Programme, 2019. HIV Med 2020; 21(11): 701-7.
[http://dx.doi.org/10.1111/hiv.13020] [PMID: 33369034]
[11]
Zhu Q, Fang P, Zhao Y, Dai D, Luo X. How about the quality and recommendation on prevention, diagnosis, and treatment of HIV/AIDS guidelines developed by WHO: A protocol for systematic review. Medicine (Baltimore) 2020; 99(52): e23638.
[http://dx.doi.org/10.1097/MD.0000000000023638] [PMID: 33350740]
[12]
Wang G, Lu C, Qin S, et al. 90-90-90 cascade analysis on reported CLHIV infected by mother-to-child transmission in Guangxi, China: a modeling study. Sci Rep 2020; 10(1): 5295.
[http://dx.doi.org/10.1038/s41598-020-62281-8] [PMID: 32210333]
[13]
Le Guillou A, Pugliese P, Raffi F, et al. Reaching the second and third joint united nations programme on HIV/AIDS 90-90-90 targets is accompanied by a dramatic reduction in primary human immunodeficiency virus (HIV) infection and in recent HIV infections in a large french nationwide HIV cohort. Clin Infect Dis 2020; 71(2): 293-300.
[http://dx.doi.org/10.1093/cid/ciz800] [PMID: 31612225]
[14]
Zhang N, Huang T, Yang XG, et al. A cross-sectional study on HIV/AIDS "90-90-90" treatment target in Shandong province, 2015. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2017; 38(10): 1367-71.
[15]
Levi J, Raymond A, Pozniak A, Vernazza P, Kohler P, Hill A. Can the UNAIDS 90-90-90 target be achieved? A systematic analysis of national HIV treatment cascades. BMJ Glob Health 2016; 1(2): e000010.
[http://dx.doi.org/10.1136/bmjgh-2015-000010] [PMID: 28588933]
[16]
Namale G, Kamacooko O, Bagiire D, et al. Sustained virological response and drug resistance among female sex workers living with HIV on antiretroviral therapy in Kampala, Uganda: a cross- sectional study. Sex Transm Infect 2019; 95(6): 405-11.
[http://dx.doi.org/10.1136/sextrans-2018-053854] [PMID: 31266818]
[17]
McCluskey SM, Siedner MJ, Marconi VC. Management of virologic failure and HIV drug resistance. Infect Dis Clin North Am 2019; 33(3): 707-42.
[http://dx.doi.org/10.1016/j.idc.2019.05.004] [PMID: 31255384]
[18]
Armenia D, Di Carlo D, Maffongelli G, et al. Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens. HIV Med 2017; 18(1): 21-32.
[http://dx.doi.org/10.1111/hiv.12388] [PMID: 27353061]
[19]
Adawaye C, Fokam J, Kamangu E, et al. Virological response, HIV-1 drug resistance mutations and genetic diversity among patients on first-line antiretroviral therapy in N’Djamena, Chad: findings from a cross-sectional study. BMC Res Notes 2017; 10(1): 589.
[http://dx.doi.org/10.1186/s13104-017-2893-1] [PMID: 29126456]
[20]
Li Y, Gu L, Han Y, et al. HIV-1 subtype B/B′ and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China. J Acquir Immune Defic Syndr 2015; 68(3): 289-97.
[http://dx.doi.org/10.1097/QAI.0000000000000473] [PMID: 25501612]
[21]
Bertagnolio S, Perno CF, Vella S, Pillay D. The impact of HIV drug resistance on the selection of first- and second-line ART in resource-limited settings. J Infect Dis 2013; 207(Suppl. 2): S45-8.
[http://dx.doi.org/10.1093/infdis/jit121] [PMID: 23687288]
[22]
Hingankar NK, Thorat SR, Deshpande A, et al. Initial virologic response and HIV drug resistance among HIV-infected individuals initiating first-line antiretroviral therapy at 2 clinics in Chennai and Mumbai, India. Clin Infect Dis 2012; 54(Suppl. 4): S348-54.
[http://dx.doi.org/10.1093/cid/cis005] [PMID: 22544202]
[23]
Kiptoo M, Brooks J, Lihana RW, et al. HIV-1 drug resistance-associated mutations among HIV-1 infected drug-naïve antenatal clinic attendees in rural Kenya. BMC Infect Dis 2013; 13: 517.
[http://dx.doi.org/10.1186/1471-2334-13-517] [PMID: 24180455]
[24]
Luo XL, Mo LD, Su GS, et al. Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy. J Pharmacol Sci 2019; 139(4): 275-9.
[http://dx.doi.org/10.1016/j.jphs.2018.11.016] [PMID: 30928089]
[25]
Phanuphak P, Sirivichayakul S, Jiamsakul A, et al. Transmitted drug resistance and antiretroviral treatment outcomes in non-subtype B HIV-1-infected patients in South East Asia. J Acquir Immune Defic Syndr 2014; 66(1): 74-9.
[http://dx.doi.org/10.1097/QAI.0000000000000108] [PMID: 24413039]
[26]
Vermund SH. Control of HIV epidemic: improve access to testing and ART. Lancet HIV 2017; 4(12): e533-4.
[http://dx.doi.org/10.1016/S2352-3018(17)30166-2] [PMID: 28867268]
[27]
Simonetti FR, Kearney MF. Review: Influence of ART on HIV genetics. Curr Opin HIV AIDS 2015; 10(1): 49-54.
[http://dx.doi.org/10.1097/COH.0000000000000120] [PMID: 25389802]
[28]
Elinav H, Pops KO, Shasha D, et al. HIV/AIDS profile and realities at a regional antiretroviral therapy clinic in Jerusalem: 12 years analysis. Scand J Infect Dis 2012; 44(1): 65-9.
[http://dx.doi.org/10.3109/00365548.2011.608713] [PMID: 21923627]
[29]
Zuo Z, Liang S, Sun X, et al. Drug resistance and virological failure among HIV-infected patients after a decade of antiretroviral treatment expansion in eight provinces of China. PLoS One 2016; 11(12): e0166661.
[http://dx.doi.org/10.1371/journal.pone.0166661] [PMID: 27997554]
[30]
Bennett DE, Myatt M, Bertagnolio S, Sutherland D, Gilks CF. Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment. Antivir Ther 2008; 13(Suppl. 2): 25-36.
[PMID: 18575189]
[31]
Lau KA, Wong JJ. Current trends of HIV recombination worldwide. Infect Dis Rep 2013; 5(Suppl. 1): e4.
[http://dx.doi.org/10.4081/idr.2013.s1.e4] [PMID: 24470968]
[32]
Wang Z, Zhang M, Zhang R, et al. Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China. BMC Infect Dis 2019; 19(1): 313.
[http://dx.doi.org/10.1186/s12879-019-3927-1] [PMID: 30961560]
[33]
Plantier JC, Leoz M, Dickerson JE, et al. A new human immunodeficiency virus derived from gorillas. Nat Med 2009; 15(8): 871-2.
[http://dx.doi.org/10.1038/nm.2016] [PMID: 19648927]
[34]
Xiao P, Zhou Y, Lu J, et al. HIV-1 genotype diversity and distribution characteristics among heterosexually transmitted population in Jiangsu province, China. Virol J 2019; 16(1): 51.
[http://dx.doi.org/10.1186/s12985-019-1162-4] [PMID: 31023323]
[35]
Vasylyeva TI, Liulchuk M, du Plessis L, et al. The Changing Epidemiological Profile of HIV-1 Subtype B Epidemic in Ukraine. AIDS Res Hum Retroviruses 2019; 35(2): 155-63.
[http://dx.doi.org/10.1089/aid.2018.0167] [PMID: 30430838]
[36]
Bbosa N, Kaleebu P, Ssemwanga D. HIV subtype diversity worldwide. Curr Opin HIV AIDS 2019; 14(3): 153-60.
[http://dx.doi.org/10.1097/COH.0000000000000534] [PMID: 30882484]
[37]
Daw MA, El-Bouzedi A, Ahmed MO, Dau AA. Molecular and epidemiological characterization of HIV-1 subtypes among Libyan patients. BMC Res Notes 2017; 10(1): 170.
[http://dx.doi.org/10.1186/s13104-017-2491-2] [PMID: 28454556]
[38]
Lu X, Zhao C, Wang W, et al. HIV-1 genetic diversity and its distribution characteristics among newly diagnosed HIV-1 individuals in Hebei province, China. AIDS Res Ther 2016; 13: 3.
[http://dx.doi.org/10.1186/s12981-015-0087-2] [PMID: 26793263]
[39]
Megens S, Laethem KV. HIV-1 genetic variation and drug resistance development. Expert Rev Anti Infect Ther 2013; 11(11): 1159-78.
[http://dx.doi.org/10.1586/14787210.2013.844649] [PMID: 24151833]
[40]
He X, Xing H, Ruan Y, et al. A comprehensive mapping of HIV-1 genotypes in various risk groups and regions across China based on a nationwide molecular epidemiologic survey. PLoS One 2012; 7(10): e47289.
[http://dx.doi.org/10.1371/journal.pone.0047289] [PMID: 23056619]
[41]
Yin YQ, Chen JS, Cheng H, et al. Transition and evolution of HIV-1 subtype among HIV-1 infections in Wuxi city, 2013-2016. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2020; 41(2): 244-8.
[42]
Yuan D, Du Z, Zhou J, et al. HIV-1 subtype diversity, drug resistance, and genetic transmission networks in men who have sex with men with virologic failure in antiretroviral therapy in Sichuan, China, 2011 to 2017. Medicine (Baltimore) 2019; 98(43): e17585.
[http://dx.doi.org/10.1097/MD.0000000000017585] [PMID: 31651864]
[43]
Chen H, Luo L, Pan SW, et al. HIV Epidemiology and Prevention in Southwestern China: Trends from 1996-2017. Curr HIV Res 2019; 17(2): 85-93.
[http://dx.doi.org/10.2174/1570162X17666190703163838] [PMID: 31269884]
[44]
Xie H, Nie J, Chen Q, Huang W, Wang Y. Comparison of the genotypic and phenotypic properties of HIV-1 standard subtype B and subtype B/B′ env molecular clones derived from infections in China. Emerg Microbes Infect 2018; 7(1): 90.
[http://dx.doi.org/10.1038/s41426-018-0087-0] [PMID: 29769530]
[45]
Lin YL, Song B, Shao B, et al. Identification of a Novel HIV-1 Unique Recombinant Form Comprising CRF01_AE, Subtype B′, and CRF65_cpx Among Men Who Have Sex with Men in Jilin, China. AIDS Res Hum Retroviruses 2018; 34(8): 714-8.
[http://dx.doi.org/10.1089/aid.2018.0109] [PMID: 29786452]
[46]
Shin KH, Lee HJ, Lee JH, Chang CL, Kim HH. Comparison of the cobas human immunodeficiency virus 1 (HIV-1) test using the cobas 4800 system with COBAS ampliPrep/COBAS TaqMan HIV-1 test and abbott realTime HIV-1 assay and performance evaluation of cobas HIV-1. Am J Clin Pathol 2019; 152(5): 558-62.
[http://dx.doi.org/10.1093/ajcp/aqz075] [PMID: 31365738]
[47]
Braun P, Delgado R, Drago M, et al. A European multicientre study on the comparison of HIV-1 viral loads between VERIS HIV-1 Assay and Roche COBAS® TAQMAN® HIV-1 test, Abbott RealTime HIV-1 Assay, and Siemens VERSANT HIV-1 Assay. J Clin Virol 2017; 92: 75-82.
[48]
Mouafo LC, Péré H, Ndjoyi-Mbiguino A, et al. LETTER TO THE EDITOR Performance of the ViroSeq® HIV-1 Genotyping System v2.0 in Central Africa. Open AIDS J 2015; 9: 9-13.
[http://dx.doi.org/10.2174/1874613601509010009] [PMID: 25767633]
[49]
Thiam M, Diop-Ndiaye H, Kebe K, et al. Performance of the ViroSeq HIV-1 genotyping system v2.0 on HIV-1 strains circulating in Senegal. J Virol Methods 2013; 188(1-2): 97-103.
[http://dx.doi.org/10.1016/j.jviromet.2012.11.044] [PMID: 23266258]
[50]
Zhao J, Chang L, Wang L. Nucleic acid testing and molecular characterization of HIV infections. Eur J Clin Microbiol Infect Dis 2019; 38(5): 829-42.
[http://dx.doi.org/10.1007/s10096-019-03515-0] [PMID: 30798399]
[51]
Yang Z, Wei S, Liu J, et al. Characterization of HIV-1 subtypes and drug resistance mutations in Henan Province, China (2017-2019). Arch Virol 2020; 165(6): 1453-61.
[http://dx.doi.org/10.1007/s00705-020-04606-6] [PMID: 32279138]
[52]
Li W, Zhu Z, Chu J, et al. Multiple HIV-1 genotypes circulating among college students in nanjing, China. AIDS Res Hum Retroviruses 2020; 36(7): 616-24.
[http://dx.doi.org/10.1089/aid.2019.0288] [PMID: 32316742]
[53]
Zhao YT, Han ZG, Wu H, et al. Characteristics and dynamics of HIV-1 subtype distribution among injected drug users in Guangzhou, 2008 - 2015. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2019; 40(12): 1629-33.
[54]
Yin Y, Liu Y, Zhu J, et al. The prevalence, temporal trends, and geographical distribution of HIV-1 subtypes among men who have sex with men in China: A systematic review and meta-analysis. Epidemiol Infect 2019; 147: e83.
[http://dx.doi.org/10.1017/S0950268818003400] [PMID: 30869019]
[55]
Sun L, Jia L, Liu Y, et al. Multiple HIV-1 subtypes were found circulating in shijingshan district of beijing, China. AIDS Res Hum Retroviruses 2019; 35(5): 494-9.
[http://dx.doi.org/10.1089/aid.2018.0263] [PMID: 30681000]
[56]
Han ZG, Zhang YL, Wu H. Characteristic and dynamic of HIV-1 subtype distribution in men who have sex with men in Guangzhou, 2008-2015. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2018; 39(1): 67-71.
[57]
Li X, Zhu K, Xue Y, et al. Multiple introductions and onward transmission of HIV-1 subtype B strains in Shanghai, China. J Infect 2017; 75(2): 160-8.
[http://dx.doi.org/10.1016/j.jinf.2017.05.009] [PMID: 28551370]
[58]
Yuan R, Cheng H, Chen LS, Zhang X, Wang B. Prevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and meta-analysis. Epidemiol Infect 2016; 144(10): 2144-53.
[http://dx.doi.org/10.1017/S0950268816000212] [PMID: 26892485]
[59]
Liang B, Yang Y, Zhang F, et al. Characterization of a Novel HIV-1 Recombinant Form (CRF01_AE/CRF07_BC/CRF08_BC) Identified from Guangxi, China. AIDS Res Hum Retroviruses 2020; 36(2): 143-52.
[http://dx.doi.org/10.1089/aid.2019.0185] [PMID: 31482724]
[60]
Jiang J, Liang B, Li K, et al. Genomic characterization of a novel HIV type 1 strain originating from CRF07_BC and CRF01_AE by heterosexual transmission in the lingshan prefecture of guangxi province, China. AIDS Res Hum Retroviruses 2020; 36(2): 153-60.
[http://dx.doi.org/10.1089/aid.2019.0182] [PMID: 31547666]
[61]
Zhang Y, Pei Z, Li H, et al. Characterization of a novel HIV-1 circulating recombinant form (CRF80_0107) among men who have sex with men in China. AIDS Res Hum Retroviruses 2019; 35(4): 419-23.
[http://dx.doi.org/10.1089/aid.2018.0226] [PMID: 30259751]
[62]
Zhang C, Feng Y, Gao L, et al. Genetic characterization and recombinant history of a novel HIV-1 circulating recombinant form (CRF101_01B) identified in Yunnan, China. Infec Gene Evolu 2019; 73: 109-12.
[63]
Miao J, Ran J, Song Y, et al. Characterization of a novel HIV-1 circulating recombinant form, CRF01_AE/B′/C (CRF96_cpx), in Yunnan, China. AIDS Res Hum Retroviruses 2018; 34(4): 393-7.
[http://dx.doi.org/10.1089/aid.2017.0288] [PMID: 29258320]
[64]
Su L, Wei D, Yang H, et al. Identification of a novel HIV-1 circulating recombinant form (CRF85_BC) in Sichuan, China. AIDS Res Hum Retroviruses 2016; 32(9): 895-9.
[http://dx.doi.org/10.1089/aid.2016.0053] [PMID: 27169981]
[65]
Han X, Takebe Y, Zhang W, et al. A large-scale survey of CRF55_01B from men-who-have-sex-with-men in China: Implying the evolutionary history and public health impact. Sci Rep 2015; 5: 18147.
[http://dx.doi.org/10.1038/srep18147] [PMID: 26667846]
[66]
Zhang W, Han X, An M, et al. Identification and characterization of a novel HIV-1 circulating recombinant form (CRF59_01B) identified among men-who-have-sex-with-men in China. PLoS One 2014; 9(6): e99693.
[http://dx.doi.org/10.1371/journal.pone.0099693] [PMID: 24978029]
[67]
Guo W, Li H, Zhuang D, et al. 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. BMC Infect Dis 2014; 14: 237.
[http://dx.doi.org/10.1186/1471-2334-14-237] [PMID: 24885612]
[68]
Gatanaga H, Ode H, Hachiya A, Hayashida T, Sato H, Oka S. Combination of V106I and V179D polymorphic mutations in human immunodeficiency virus type 1 reverse transcriptase confers resistance to efavirenz and nevirapine but not etravirine. Antimicrob Agents Chemother 2010; 54(4): 1596-602.
[http://dx.doi.org/10.1128/AAC.01480-09] [PMID: 20124001]
[69]
Megens S, De Wit S, Bernatchez J, et al. Characterization of amino acids Arg, Ser and Thr at position 70 within HIV-1 reverse transcriptase. Acta Clin Belg 2014; 69(5): 348-57.
[http://dx.doi.org/10.1179/2295333714Y.0000000038] [PMID: 25103592]
[70]
Xu HT, Colby-Germinario SP, Oliveira M, et al. The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity. J Virol 2014; 88(3): 1536-47.
[http://dx.doi.org/10.1128/JVI.02904-13] [PMID: 24227862]
[71]
Yap SH, Herman BD, Radzio J, Sluis-Cremer N, Tachedjian G. N348I in HIV-1 reverse transcriptase counteracts the synergy between zidovudine and nevirapine. J Acquir Immune Defic Syndr 2012; 61(2): 153-7.
[http://dx.doi.org/10.1097/QAI.0b013e3182657990] [PMID: 22743599]
[72]
Li HP, Han Y, Zhu XP, et al. Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2011; 32(9): 908-12.
[73]
Sluis-Cremer N, Moore K, Radzio J, Sonza S, Tachedjian G. N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations. AIDS 2010; 24(2): 317-9.
[http://dx.doi.org/10.1097/QAD.0b013e3283315697] [PMID: 20010074]
[74]
Biondi MJ, Beilhartz GL, McCormick S, Götte M. N348I in HIV-1 reverse transcriptase can counteract the nevirapine-mediated bias toward RNase H cleavage during plus-strand initiation. J Biol Chem 2010; 285(35): 26966-75.
[http://dx.doi.org/10.1074/jbc.M110.105775] [PMID: 20530477]
[75]
Ehteshami M, Beilhartz GL, Scarth BJ, et al. Connection domain mutations N348I and A360V in HIV-1 reverse transcriptase enhance resistance to 3′-azido-3′-deoxythymidine through both RNase H-dependent and -independent mechanisms. J Biol Chem 2008; 283(32): 22222-32.
[http://dx.doi.org/10.1074/jbc.M803521200] [PMID: 18547911]
[76]
Yap SH, Sheen CW, Fahey J, et al. N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med 2007; 4(12): e335.
[http://dx.doi.org/10.1371/journal.pmed.0040335] [PMID: 18052601]