Non-nucleoside reverse transcriptase inhibitors
|Mutations associated with resistance||Mutations associated with « possible resistance »|
E138K [12, 13]
|NVP|| A98S (for HIV-1 subtype C only) |
|ETR|| At least 3 among: V90I, A98G, L100I, K101E/H/I/P/R, V106I, V179D/F/I/L/M/T, G190A/S, M230L [4, 7, 8, 9, 10, 11]|
E138K [12, 13]
Y181C/I/V [5, 6]
| 2 mutations among: V90I, A98G, L100I, K101E/H/I/P/R, V106I, V179D/F/I/L/M/T, G190A/S, M230L [4, 7, 8, 9, 10, 11]|
E138A/G/Q/R/S [5, 6, 7, 8]
|RPV|| K101E/P [9, 13]|
E138A/G/K/Q/R/S [12, 13, 14]
L100I + K103N/S [9, 15]
L100I + K103R + V179D 
|DOR|| V106A/M [17, 18, 19, 20, 21]|
L100I + K103N [17, 19]
K103N + Y181C
K103N + P225H
At least 4 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y 
| At least 2 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y |
EFV: efavirenz, NVP: nevirapine, ETR: etravirine, RPV : rilpivirine, DOR : doravirine.
For DNA provirus, impact of stop codons and G->A mutations on ARV resistance is unknown.
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2/ Brenner B et al. A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors. AIDS. 2003 Jan 3;17(1):F1-5.
3/ Deshpande A et al. Resistance mutations in subtype C HIV type 1 isolates from Indian patients of Mumbai receiving NRTIs plus NNRTIs and experiencing a treatment failure: resistance to AR. AIDS Res Hum Retroviruses 2007; 23 : 335-40
4/ Vingerhoets J et al. Impact of baseline NNRTI mutations on the virological response to TMC125 in the Phase III clinical trials DUET-1 and DUET-2. XVI International HIV drug resistance workshop : basic principles and clinical implications, 12-16 June 2007, Barbados, West Indies, abstract 32
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9/ Azijn H et al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27.
10/ Marcelin AG et al. Mutations selected in patients displaying treatment failure under an etravirine-containing regimen. Antiviral Therapy 2011; 10.3851/IMP1886.
11/ Maïga AI et al. Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes. Antimicrob Agents Chemother. 2010 Feb;54(2):728-33.
12/ Asahchop EL et al. Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. Antimicrob Agents Chemother. 2011 Feb;55(2):600-7.
13/ Eron J et al. Characterization of the resistance profile of TMC278: 48-week analysis of the Phase III studies ECHO and THRIVE. 50th ICAAC 2010 (abstract H-1810).
14/ Haddad M et al. Impact of HIV-1 reverse transcriptase E138 mutations selected on rilpivirine drug susceptibility. Antiviral Therapy 2011; 16 Suppl 1: A18 (abstract 10).
15/ Haddad M et al. Combinations of HIV-1 reverse transcriptase mutations L100I+K103N/S and L100I+K103R+V179D reduce susceptibility to rilpivirine. 53rd ICAAC 2013 (abstract H-677).
16/ Melikian et al. Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother. 2014 Jan;69(1):12-20.
17/ Lai MT et al. In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2014;58(3):1652-63.
18/ Feng M, et al. In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. Antimicrob Agents Chemother. 2015 Jan;59(1):590-8.
19/ Feng M, et al. Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2241-7.
20/ Smith SJ, et al. Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants. J Acquir Immune Defic Syndr. 2016 Aug 15;72(5):485-91.
21/ Lai MT et al. Characterization of Doravirine-Selected Resistance Patterns from Participants in Treatment-Naïve Phase 3 Clinical Trials. Abstract THPDB0101. 22nd International AIDS Conference, Amsterdam, the Netherlands, 23-27 July 2018.
22/ Raymond S et al. Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen.
Clin Infect Dis. 2018 May 2;66(10):1588-1594.
23/ Saladini F et al. In vitro analysis of doravirine activity on HIV-1 clones harboring multiple NNRTI resistance mutations. Abstract PS5/6, EACS 2019, Basel, Switzerland, Nov 6-9, 2019