Nucleoside and nucleotide reverse transcriptase inhibitors
Mutations associated with resistance | Mutations associated with « possible resistance » | |
ZDV | T215A/C/D/E/G/H/I/L/N/S/V/Y/F [1, 2, 3, 4] At least 3 mutations among: M41L, D67N, K70R, L210W, K219Q/E [1, 2, 3, 4] Q151M Insertion at codon 69 | |
3TC/FTC | K65R [8, 9, 11] M184V/I Insertion at codon 69 | Q151M |
ABC | At least 3 mutations among: M41L, D67N, M184V/I, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F [5, 20] K65R [6, 8, 9, 24] L74V/I [16, 17, 18, 19, 20, 24] Y115F [24] Q151M Insertion at codon 69 | 2 mutations among: M41L, D67N, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F [5, 20] M184V/I [24] |
TDF/TAF | At least 4 mutations among: M41L, E44D, D67N, T69D/N/S, L74V/I, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F [10, 12, 21, 25, 26] K65R/E/N [6, 7, 8, 9, 22, 23, 25, 26] Insertion at codon 69 K70E [13, 14, 15] | 3 mutations among: M41L, E44D, D67N, T69D/N/S, L74V/I, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F [10, 12, 21, 25, 26] |
ISL | M184V/I [27,28,29] | A114S [29] |
ZDV: zidovudine, 3TC: lamivudine, FTC: emtricitabine, ddI: didanosine, d4T: stavudine, ABC: abacavir, TDF: tenofovir, TAF : tenofovir alafenamide, ISL: islatravir.
For didanosine and stavudine refer to previous rules (See Archives, September 2017, version 27)
For DNA provirus, impact of stop codons and G->A mutations on ARV resistance is unknown.
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9/ Parikh et al. K65R : a multi-nucleoside resistance mutation of a low but increasing frequency. XII International HIV drug resistance workshop : basic principles and clinical implications, 10-14 June 2003, Los Cabos, Mexico, abstract 136.
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16/ Miller V et al. HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. AIDS 2000; 14:163–171.
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20/ Wirden et al. Risk factors for selection of the L74I reverse transcriptase mutation in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 2006 Jul;50(7):2553-6.
21/ Wirden M, et al. Antiretroviral combinations implicated in emergence of the L74I and L74V resistance mutations in HIV-1-infected patients. AIDS. 2009 Jan 2;23(1):95-9.
22/ Fourati S et al. Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors. J Antimicrob Chemother. 2013 Jun 19.
23/ Ross LL et al. A rare HIV reverse transcriptase mutation, K65N, confers reduced susceptibility to tenofovir, lamivudine and didanosine. AIDS 2006 Mar 21;20(5):787-9.
24/ Tisdale M et al. Combination of mutations in human immunodeficiency virus type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89. Antimicrob Agents Chemother. 1997 May;41(5):1094-8.
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27/ Kawamoto et al. 2008. 2′-Deoxy-4′-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants. Int J Biochem Cell Biol. 40, 2410–2420.
28/ Takamatsu et al. 2018 The high genetic barrier of EFdA/MK-8591 stems from strong interactions with the active site of drug-resistant HIV-1 reverse transcriptase. Cell Chem Biol. 2018; 25(10): 1268–1278.e3. doi:10.1016/j.chembiol.2018.07.014.
29/ Diamond T et al. Islatravir selects for HIV 1 variants in MT4 GFP cells that profoundly reduce replicative capacity in peripheral blood mononuclear cells. HIV Glasgow 2020. P120.