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HIV-2

NUCLEOSIDE AND NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS [1]
Mutations associated with resistance Mutations associated with « possible resistance »
ZDV Q151M
S215A/C/F/L/Y + 1 mutation among K65R, N69S/T, K70R, Y115F, K223R 		S215A/C/F/L/Y
3TC/FTC M184I/V K65R
ABC K65R
Q151M
M184I/V + 1 mutation among: L74V, Y115F 		  2 mutations among: D67N, K70N/R, M184V/I, S215A/C/F/L/Y
TDF/TAF K65R
Q151M + V111I
ZDV: zidovudine, 3TC: lamivudine, FTC: emtricitabine, ABC: abacavir, TDF: tenofovir, TAF : tenofovir alafenamide Didanosine and stavudine are not recommended.

PROTEASE INHIBITORS [1]
Mutations associated with resistance Mutations associated with « possible resistance »
LPV  2 mutations among: I82F, I84V, L90M
 I54M
 V47A 		 V62A + L99F
 1 mutation among: I82F, I84V, L90M
DRV  I50V
 I54M
 I84V + L90M 		 1 mutation among: I84V, L90M
LPV: lopinavir, DRV : darunavir For indinavir and saquinavir refer to previous rules (Version 27, September 2017). Atazanavir and tipranavir are not recommended.

INTEGRASE STRAND TRANSFER INHIBITORS [1-6]
Mutations associated with resistance Mutations associated with « possible resistance »
RAL  N155H/R
 Q148K/R/H [3,4,5]
 E92Q + T97A
 Y143C/G/R + 1 mutation among: E92Q, T97A
 Insertion at codon 231 [5] 		 E92Q
 Y143C/G/R
 G118R [6]
 R263K [6,7]
EVG  E92G/Q
 Q148K/R/H [3,4,5]
 N155H
 T97A + Y143C
 Insertion at codon 231 [5]
 G118R [6]
 R263K [6,7] 		 Y143C
DTG  Q148K
 G140S + Q148R/H [3,4,5]
 E92Q + N155H
 T97A + N155H
 Insertion at codon 231 [5]
 G118R [6]
 R263K [6,7] 		 Q148R/H [3]
 N155H
 E92Q
 T97A + Y143C
CAB*  Q148K
 G140S + Q148R/H [3,4,5]
 E92Q + N155H
 T97A + N155H
 Insertion at codon 231 [5]
 G118R [6]
 R263K [6,7] 		 Q148R/H [3]
 N155H
 E92Q
 T97A + Y143C
BIC*  Q148K
 G140S + Q148R/H [3,4,5]
 E92Q + N155H
 T97A + N155H
 G118R [6]
 R263K [6,7] 		 Q148R/H [3]
 N155H
 E92Q
 T97A + Y143C
 Insertion at codon 231 [5]
RAL: raltegravir, EVG : elvitegravir, DTG: dolutegravir, CAB: cabotegravir, BIC: bictegravir *Due to the very close structures of dolutegravir and cabotegravir, rules for dolutegravir are transposed to cabotegravir with the exception of the insertion at codon 231 for bictegravir.

NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
 Naturally resistant to all NNRTI [2]
FUSION INHIBITOR
 Naturally resistant to enfuvirtide [2]
ATTACHMENT INHIBITOR
 Naturally resistant to fostemsavir [8]


CAPSID INHIBITORS
Mutations associated with resistance Mutations associated with « possible resistance »
LEN  N73D [9]  Q66H [9]
 R69K [9]
 A76V [9]
LEN: lenacapavir

1/ Charpentier C et al. HIV-2EU-Supporting Standardized HIV-2 Drug-Resistance Interpretation in Europe: An Update. Clin Infect Dis. 2015 Jul 17. pii: civ572

2/ Witvrouw E et al. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther 2004; 9(1): 57-65.

3/ Smith RA et al. Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. PLoS ONE, 2012; 7.

4/ Smith RA, In vitro antiviral activity of cabotegravir against HIV-2. Antimicrob Agents Chemother. 2018 Jul 16. pii: AAC.01299-18. doi: 10.1128/AAC.01299-18.

5/ Le Hingrat Q et al. A 5 amino-acid insertion in the C-terminal region of HIV-2 integrase impacts phenotypic susceptibility to the five integrase inhibitors. 16th European Meeting on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance, May 2018, Roma, Italy, Abstract 4.

6/ Smith RA, Wu VH, Song J, et al. Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants. J Infect Dis. 2022 Aug 26;226(3):497-509. doi: 10.1093/infdis/jiac037.

7/ Requena S, Lozano AB, Caballero E, et al. Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain. J Antimicrob Chemother. 2019 May 1;74(5):1357-1362.

8/ Lataillade M et al. Viral drug resistance through 48 weeks, in a phase 2b, randomized, controlled trial of the HIV-1 attachment
 inhibitor prodrug, Fostemsavir. J Acquir Immune Defic Syndr. 2018 Mar 1;77(3):299-30

9/ Bertine M. et al. Rapid Selection of HIV-2 Capsid Mutations After Failure of a Lenacapavir-Containing Regimen, CROI 2024, Abstr. 682