Integrase strand transfer inhibitors
| Mutations associated with resistance | Mutations associated with « possible resistance » | |
| RAL |  T66A/K [10,40] E92Q [1, 2] G118R [10,17] F121Y [10,17] G140A/S [7] Y143A/C/G/H/R/S [1, 3, 4, 5, 8, 14] N144D [42] Q148E/G/H/K/R [1, 2] V151L [9] N155H/S/T [1, 2, 9] E157Q [2] S230R [18, 31, 32, 33] R263K [16,18] L74F/I + V75I [36] | |
| EVG |
| |
| DTG* 50 mg QD |
|
|
| DTG* 50 mg BID | G118R [12,13] F121Y [17] N144D [42] V151L [9,23] S153F/Y [9, 23, 26, 34] R263K [16] T66K + L74M [9] E92Q + N155H [9, 21, 22] Q148H/K/R + at least 2 mutations among: L74I or T97A or E138A/K/T or G140A/C/S [15, 38, 39] Q148H/K/R + N155H [9, 27,28] | T66K [9] Q148H/K/R + 1 mutation among: L74I or E138A/K/T or G140A/C/S [15] At least 4 mutations among: L74I/M, T97A, E138K, S147G, N155H [43] |
| CAB** | G118R [12,13] F121Y [17] E138A/K/T G140A/C/R/S [37] N144D [42] Q148H/K/R [15] V151L [9, 23] S153F/Y [9, 23, 26, 34] N155H [18] S230R [29] R263K [16] T66K + L74M [9] L74I + E92Q [30] | T66K [9] At least 3 mutations among: L74M, E92Q, T97A, S147G [43] |
| BIC** | G118R [12,13] F121Y [17] E138A/K/T G140A/C/S N144D [42] Q148H/K/R V151L [9, 23] S153F/Y [9, 23, 26, 34] N155H [18] S230R [29] R263K [16] T66K + L74M [9] L74I + E92Q [30] | T66K [9] At least 3 mutations among: L74M, E92Q, T97A, S147G [43] |
RAL: raltegravir, EVG: elvitegravir, DTG: dolutegravir, CAB: cabotegravir, BIC: bictegravir.
* Please note that rules are different for DTG 50 mg BID and DTG 50 mg QD.
**Due to few data and to the very close structures of dolutegravir, cabotegravir and bictegravir some rules for dolutegravir QD are transposed to cabotegravir and bictegravir.
For DNA provirus, impact of stop codons and G->A mutations on ARV resistance is unknown
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21/ Underwood et al.The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):297-301.
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24/ Margolis et al. 744 and Rilpivirine As Two Drug Oral Maintenance Therapy: LAI116482 (LATTE) Week 48 Results. CROI 2014. Abstract Number: 91LB
25/ Dudas et al. Characterization of NNRTI and INI Resistance Mutations Observed in a Study Subject on Oral Two-Drug Maintenance Therapy with 10 mg Cabotegravir + 25 mg Rilpivirine. IHDRW 2015 Seattle, WA, USA. Abstract 13.
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http://s3-eu-west-1.amazonaws.com/hivglasgow/wp-content/uploads/2016/12/07153921/3.-Treatment-Strategies-Target-Populations_Poster-Book.pdf
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33/ Pham HT et al. Characterization of the dolutegravir monotherapy-acquired S230R resistance mutation. CROI March 4-7, 2018, Boston, MA, USA. Abstract 548.
34/ Andreatta K et al. Integrase inhibitor resistance selections initiated with drug resistant HIV-1. CROI March 4-7, 2018, Boston, MA, USA. Abstract 546.
35/ Charpentier C et al. Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen. J Antimicrob Chemother. 2018 Apr 1;73(4):1039-1044.
36/ Hachiya A et al. Impact of clinically observed integrase mutations on dolutegravir. CROI February 13–16, 2017, Seattle, WA, USA. Abstract 496.
37/ Orkin C et al. Long-acting CABOTEGRAVIR + RILPIVIRINE for HIV maintenance: FLAIR Week 48 results. CROI 2019, Seattle, WA, USA. Abs. 140LB.
38/ George JM et al. Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir. Open Forum Infect Dis. 2018 Sep 8;5(10):221.
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41/ Goethals O et al. Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Virology. 2010 Jul 5;402(2):338-46.
42/ Andreatta K et al. Long-term Bictegravir and Dolutegravir Resistance Selections Initiated with HIV-1 Containing M184V in Reverse Transcriptase. Abstract 9. European Meeting on HIV & Hepatitis 2020.
43/ Wirden M et al. Role of Dolutegravir in the emergence of the S147G integrase resistance mutation. CROI March 3-6, 2024, Denver, CO, USA, Poster 683.