Interpretation du genotype

September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: NUCLEOSIDE AND NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
T215Y/F
T215A/C/D/E/G/H/I/L/N/S/V [1, 2, 3, 4]
At least 3 mutations among: M41L, D67N, K70R, L210W,
T215A/C/D/E/G/H/I/L/N/S/V, K219Q/E [1, 2, 3, 4]
Q151M
Insertion at codon 69
M184V/I
K65R [11, 12, 16]
Insertion at codon 69
Q151M
At least a score of + 2 among: M41L + T69D + 215Y/F + K219Q/E – K70R
K65R [11, 12]
– M184 V/I [5, 14, 15, 17, 18]
L74V/I [19]
Q151M
Insertion at codon 69
V75A/M/S/T
T215A/C/D/E/G/H/I/L/N/S/V [4, 7]
T215Y/F [6]
At least 3 mutations among: M41L, D67N, K70R, L210W,
T215A/C/D/E/G/H/I/L/N/S/V, K219Q/E [4, 7, 14, 15]
K65R [30, 31, 32]
Q151M
Insertion at codon 69
At least 4 mutations among: M41L, D67N, M184V/I, L210W, T215Y/F [8,
3 mutations among: M41L, D67N, M184V/I, L210W,
T215Y/F [8, 19, 29]
K65R [9, 11, 12]
L74V/I [24, 25, 26, 27, 28, 29]
Y115F
Q151M
Insertion at codon 69
At least 6 mutations among: M41L, E44D, D67N, T69D/N/S, L74V/I,
3, 4 or 5 mutations among: M41L, E44D, D67N,
L210W, T215Y/F [13, 20, 33]
T69D/N/S, L74V/I, L210W, T215Y/F [13, 33]
K65R/E [9, 10, 11, 12, 34]
Insertion at codon 69
K70E [21, 22, 23]
ZDV: zidovudine, 3TC: lamivudine, FTC: emtricitabine, ddI: didanosine, d4T: stavudine, ABC: abacavir, TDF: tenofovir
September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
L100I
K101E
K103H/N/S/T [1]
V106M [2]
E138K [12, 13]
Y181C/I
Y188C/L
G190A/C/E/Q/S/T/V
P225H
M230L
A98S (for HIV-1 subtype C only) [3]
E138K [13]
L100I
K101E
K103H/N/S/T [1]
V106A/M [2]
Y181C/I
Y188C/H/L
G190A/C/E/Q/S/T/V
M230L

At least 4 among: V90I, A98G, L100I, K101E/H/I/P/R,
3 mutations among: V90I, A98G, L100I, K101E/H/I/P/R, V106I,
V106I, V179D/F/I/L/M/T, Y181C/I, G190A/S, M230L [4, 7, 8,
V179D/F/I/L/M/T, Y181C/I, G190A/S, M230L [4, 7, 8, 9, 10, 11]
9, 10, 11]
E138K [12, 13]
E138A/G/Q/R [5, 6, 7, 8]
Y181V [5, 6]
Y181C+H221Y [7]
K101E/P [9, 13]
E138A/G/K/Q/R/S [12, 13, 14]
V179L [9]
Y181C/I/V [13]
Y188L [9]
H221Y [13]
M230I/L/V [9]
L100I + K103N/S [9, 15]
L100I + K103R + V179D [15]
EFV: efavirenz, NVP: nevirapine, ETR: etravirine, RPV : rilpivirine
September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: PROTEASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
M46I/L
V82A/F/M/S/T [11]
I84A/V [8]
L90M and at least 2 among: K20M/R, L24I, V32I, M36I, I54V/L/M/T,
A71V/T, G73S/A, V77I
At least 4 mutations among: L10F/I/M/R/V, I15A/V, K20I/M/R/T, L24I,
3 mutations among: L10F/I/M/R/V, I15A/V, K20I/M/R/T, L24I, I62V,
1000/100 mg BID
I62V, G73S/T, V82A/F/S/T, I84V, L90M [9]
G73S/T, V82A/F/S/T, I84V, L90M [9]
V82A/F/S/T and at least 2 among: L10I, M36I, M46I/L, I54V/L/M/T,
I84A/V [8]
A71V/T, V77I [1]
L90M
I50V
V32I and I47A/V [2, 13, 14]
At least 4 mutations among: L10F/I/V, L33F, M36I,
700/100 mg BID
I54A/L/M/S/T/V, I62V, V82A/C/F/G, I84V, L90M [2, 20]
At least 6 mutations among: L10F/I/R/V, K20M/R, L24I, L33F, M46I/L,
4 or 5 mutations among: L10F/I/R/V, K20M/R, L24I, L33F, M46I/L,
I50V, F53L, I54M/L/T/V, L63P, A71I/L/V/T, V82A/F/S/T, I84V, L90M [3, 4,
I50V, F53L, I54M/L/T/V, L63P, A71I/L/V/T, V82A/F/S/T, I84V, L90M
[3, 4, 5, 21]
I47A [15, 16]
L76V [18, 19]
300/100 mg QD
N88S [28,29,30]
At least 3 mutations among: L10F/I/V, G16E, L33F/I/V, M46I/L, D60E,
I84V, I85V, L90M [7, 12, 22]

At least a score of + 3*: 36I/L/V – 53L/W/Y + 58E + 69I/K/N/Q/R/Y +
A score of + 2*: 36I/L/V – 53L/W/Y + 58E + 69I/K/N/Q/R/Y +
89I/M/R/T/V [10, 23]
89I/M/R/T/V [10, 23]
500/200 mg BID
At least 4 mutations among: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P,
3 mutations among: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P,
L76V, I84V, L89V [17, 24, 25, 26]
L76V, I84V, L89V [17, 24, 25, 26]
600/100 mg BID
IDV: indinavir, SQV: saquinavir, NFV: nelfinavir, RTV: ritonavir, FPV: fosamprenavir, LPV: lopinavir, ATV:atazanavir, TPV: tipranavir, DRV : darunavir

* Insufficient data for HIV-1 subtype non-B

September 2013- Version n°23
ANRS - AC 11: RESISTANCE GROUP
GENOTYPE INTERPRETATION: FUSION INHIBITOR
Mutations associated with resistance
G36A/D/E/S/V [1, 2, 3, 4, 5, 6, 7]
V38A/E/K/M
Q40H/K/P/T
N42D/T
N43D/H/K/S
L45Q/M
ENF (T20): enfuvirtide
September 2013- Version n°23
ANRS - AC 11 : RESISTANCE GROUP
GENOTYPE INTERPRETATION: INTEGRASE INHIBITORS
Mutations associated with resistance
Mutations associated with « possible resistance »
T66K [10]
E92Q [1, 2]
G118R [10]
F121Y [10]
G140A/S [7]
Y143A/C/G/H/R/S [1, 3, 4, 5, 8, 14]
Q148E/G/H/K/R [1, 2]
V151L [9]
N155H/S/T [1, 2, 9]
E157Q [2]
T66I/A/K [6]
E92Q [6]
F121Y [9]
E138K
G140C/S
Y143A/C/G/H/R/S [14]
P145S [9]
S147G
Q148H/R/K [6]
V151L [9]
N155H/S/T [6,9]
E157Q [11]
G118R [12,13]
T66K [9]
V151L [9]
S153F
S153Y
Q148H/K/R + 1 mutation among: L74I or E138A/K/T or
T66K + L74M
G140A/C/S [15]
E92Q + N155H
Q148H/K/R + at least 2 mutations among: L74I
or E138A/K/T or G140A/C/S [15]
Q148R + N155H
R263K [16]
RAL: raltegravir, EVG: elvitegravir, DTG: dolutegravir
September 2013- Version n°23
ANRS - AC 11 : RESISTANCE GROUP
GENOTYPE INTERPRETATION FOR HIV-2
NUCLEOSIDE AND NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS

K65R : resistance to ddI, TDF, ABC [1]
Q151M : all NRTI except 3TC and FTC [1]
M184V : resistance to 3TC/FTC [1]
S215A/C/F/L/P/Y : resistance to AZT and d4T [1]
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Naturally resistant to all NNRTI [2, 3]

PROTEASE INHIBITORS

Naturally resistant to APV and fosAPV [2, 3]
Contradictory data for ATV , TPV [2, 4]

FUSION INHIBITOR

Naturally resistant to T20 [2, 3]
INTEGRASE INHIBITORS

Y143C/H/R : resistance to raltegravir [7]
Q148K/R : resistance to raltegravir [5]
N155H : resistance to raltegravir [6]
September 2013- Version n°23
REFERENCES
Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
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15/ Friend J et al. Isolated lopinavir resistance after virological rebound of a ritonavir/lopinavir-based regimen. AIDS. 2004 Sep 24;18(14):1965-6. 16/ de Mendoza C et al. Prevalence of the HIV-1 protease mutation I47A in clinical practice and association with lopinavir resistance. AIDS 2006 Apr 24; 20(7): 1071-4. 17/ de Meyer S, Vangeneugden T, van Baelen B, de Paepe E, van Marck H, Picchio G, Lefebvre E, de Béthune MP. Resistance profile of darunavir: combined 24-week results from the POWER trials. AIDS Res Hum Retroviruses. 2008 Mar;24(3):379-88. 18/ Nijhuis N et al. A novel genetic pathway involving L76V and M46I leading to lopinavir/r resistance. XVI International HIV drug resistance workshop : basic principles and clinical implications, 12-16 June 2007, Barbados, West Indies, abstract 127. 19/ Delaugerre C et al. Protease inhibitor resistance analysis in the MONARK trial comparing first-line lopinavir-ritonavir monotherapy to lopinavir-ritonavir plus zidovudine and lamivudine triple therapy. Antimicrob Agents Chemother. 2009 Jul;53(7):2934-9. 20/ Marcelin AG et al. Genotypic resistance analysis of the virological response to fosamprenavir-ritonavir in protease inhibitor-experienced patients in CONTEXT and TRIAD clinical trials. Antimicrob Agents Chemother. 2008 Dec;52(12):4251-7. 21/ Hill A et al. Identification of new genotypic cut-off levels to predict the efficacy of lopinavir/ritonavir and darunavir/ritonavir in the TITAN trial. HIV Med. 2009 Jul 6. 22/ Di Giambenedetto S et al. A rigorous statistical learning method for the estimation and validation of weighted drug susceptibility scores applied to in vivo virological outcome prediction in atazanavir/ritonavir-containing HAART. XVII International HIV drug resistance workshop : basic principles and clinical implications, 10-14 June 2008, Sitges, Spain, abstract 95. 23/ Bethell R et al. No effect of subtype on susceptibility and virological response to TPV/r for treatment experienced patients. XVII International HIV drug resistance workshop : basic principles and clinical implications, 10-14 June 2008, Sitges, Spain, abstract 111. 24/ Descamps D et al. Mutations associated with virological response to darunavir/ritonavir in HIV-1-infected protease inhibitor-experienced patients. J Antimicrob Chemother. 2009 Mar;63(3):585-92. 25/ De Meyer S. et al. Influence of baseline protease inhibitor resistance on the efficacy of darunavir/ritonavir or lopinavir/ritonavir in the TITAN trial. J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):563-4. 26/ De Meyer S. et al. Phenotypic and genotypic determinants of resistance to darunavir: analysis of data from treatment-experienced patients in POWER 1, 2, 3 and DUET-1 and 2. XVII International HIV drug resistance workshop : basic principles and clinical implications, 10-14 June 2008, Sitges, Spain, abstract 31. 27/ De Meyer S. et al. Confirmation of the negative impact of protease mutations I47V, I54M, T74P and I84V and the positive impact of protease mutation V82A on virological response to darunavir/ritonavir. XVII International HIV drug resistance workshop : basic principles and clinical implications, 9-13 June 2009, Fort Myers, Florida, abstract 126. September 2013- Version n°23
28/ Gong YF. Et al. In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632. Antimicrob Agents Chemother. 2000 Sep;44(9):2319-26. 29/ Malan DR; et al. Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients. J Acquir Immune Defic Syndr. 2008 Feb 1;47(2):161-7. 30/ Malan DR et al. 96-week efficacy and safety of atazanavir, with and without ritonavir, in a HAART regimen in treatment-naive patients. J Int Assoc Physicians AIDS Care (Chic). 2010 Jan-Feb;9(1):34-42. Fusion inhibitor
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Integrase inhibitors

1/ Cooper DA et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65.
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8/Huang W et al. Identification of alternative amino acid substitutions at HIV-1 integrase codon 143 that confer reduced susceptibility to raltegravir. 18th
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14/ Huang W et al. Contribution of raltegravir selected secondary mutations to reduction in elvitegravir susceptibility of patient-derived HIV integrase containing
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2013 Toronto, Canada, Abstract 21.
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Source: http://www.hivfrenchresistance.org/2013/Algo-sep-2013.pdf

Swine flu & you

Swine Flu & You Information for People Living in Orange County What is swine flu? Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza viruses. Outbreaks of swine flu happen regularly in pigs. People do not normally get swine flu, but human infections can and do happen. Most commonly, human cases of swine flu happen in people who are around pigs b

261151 106.110

Psychopharmacology (2002) 163:106–110DOI 10.1007/s00213-002-1151-xO R I G I N A L I N V E S T I G A T I O NCatherine J. Harmer · Zubin Bhagwagar ·Phillip J. Cowen · Guy M. GoodwinAcute administration of citalopram facilitates memory consolidationin healthy volunteersReceived: 8 February 2002 / Accepted: 8 May 2002 / Published online: 29 June 2002 Springer-Verlag 2002Abstract Objectives:

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