Katholieke Universiteit Leuven
Rega Institute for Medical Research and University Hospitals Leuven
Microbiology and Immunology
Clinical and Epidemiological Virology
Kristel Van Laethem and Anne-Mieke Vandamme
www.kuleuven.ac.be/rega/cev/links/
kristel.vanlaethem@uz.kuleuven.ac.be
Algorithm for the use of genotypic resistance data
Rega v6.3, July 9, 2004
Criteria to consider an isolate resistanta,b,c,dCriteria to consider an isolate intermediate resistant

b,c,d

NRTI
zidovudine[at least 1 mutation of (T69X-XX,Q151M)]
or (T215F/Y and not M184I/V)
or [at least 2 mutations of (M41L,D67N,T69A/N,K70R,L210W,T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R) and not M184I/V]
or [at least 2 mutations of (M41L,D67N,T69A/N,K70R,L210W,T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R) and M184I/V and G333D/E]
or [at least 3 mutations of (M41L,D67N,T69A/N,K70R,L210W,T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R) and M184I/V][1 mutation of (M41L,D67N,T69A/N,K70R,L210W,T215A/C/D/E/G/I/L/N/S/V,
K219E/H/N/Q/R) and not M184I/V]
or [1 mutation of (M41L,D67N,T69A/N,K70R,L210W,T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R) and M184I/V and G333D/E]
or [2 mutations of (M41L,D67N,T69A/N,K70R,L210W,
T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R) and M184I/V]

zalcitabineat least 1 mutation of (K65R,D67G,∆67,T69D/G/N/S,T69X-XX,L74V,V75T,Q151M)

M184I/Vor [at least 4 mutations of (M41L,D67N,T69A,K70R,L210W,T215F/Y,K219E/H/N/Q/R)]

didanosine

at least 1 mutation of (K65R,T69G/N,T69X-XX,L74V,Q151M)[at least 1 mutation of (V75T,M184I/V)]or [at least 4 mutations of(M41L,D67N,T69A/D,K70R,L210W,T215F/Y,K219E/H/N/Q/R)]

lamivudine

M184I/Vor (K65R and Q151M)[at least 1 mutation of (∆67,T69X-XX)]or [1 mutation of (K65R,Q151M)]
or {[at least 1 mutation of (E44A/D,V118I)] and [at least 3 mutations of(M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/H/N/Q/R)]}

stavudine[at least 1 mutation of (∆67,T69G,T69X-XX,V75A/M/S/T,Q151M)]
or [at least 4 mutations of(M41L,D67N,T69A/D/N,K70R,L210W,T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R)]

3 mutations of (M41L,D67N,T69A/D/N,K70R,L210W,
T215A/C/D/E/G/I/L/N/S/V/F/Y,K219E/H/N/Q/R)

Rega v6.3 - 1

[1 mutation of (T69X-XX,Q151M)]
or {[at least 1 mutation of (K65R,L74V,Y115F,M184I/V)] and [at least 1 mutation of(M41L,D67N,K70R,L210W,T215F/Y,K219E/H/N/Q/R]}or [at least 3 mutations of (M41L,D67N,K70R,L210W,T215F/Y,K219E/H/N/Q/R)]

abacavir[at least 1 mutation of (∆67,T69G)]or [at least 2 mutations of (K65R,T69X-XX,L74V,Y115F,Q151M,M184I/V)]or {[at least 1 mutation of (T69X-XX,Q151M)] and [at least 3 mutations of(M41L,D67N,K70R,L210W,T215F/Y,K219E/H/N/Q/R)]}or {[at least 1 mutation of (K65R,L74V,Y115F,M184I/V)] and [at least 4 mutations of(M41L,D67N,K70R,L210W,T215F/Y,K219E/H/N/Q/R]}

emtricitabine

M184I/Vor (K65R and Q151M)[at least 1 mutation of (∆67,T69X-XX)]or [1 mutation of (K65R,Q151M)]
or {[at least 1 mutation of (E44A/D,V118I)] and [at least 3 mutations of(M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/H/N/Q/R)]}[at least 1 mutation of (K65R,T69X-XX)]or [at least 6 mutations of (M41L,D67N,K70R,L210W,T215Y/F,K219E/H/N/Q/R) and not
M184I/V][at least 1 mutation of (L74V,Q151M)]
or [M41L and at least 2 mutations of (D67N,K70R,L210W,T215Y/F,K219E/H/N/Q/R)
and not M184I/V]
or [L210W and at least 2 mutations of (M41L,D67N,K70R,T215Y/F,K219E/H/N/Q/R)
and not M184I/V]
or [(M41L or L210W) and T215Y/F and at least 1 mutation of(D67N,K70R,K219E/H/N/Q/R) and not M184V/I]
or [at least 6 mutations of (M41L,D67N,K70R,L210W,T215Y/F,K219E/H/N/Q/R) andM184I/V]

nevirapine[at least 1 mutation of(L100I,K103H/N/S/T,V106A/M,Y181C/I,Y188C/H/L,G190A/C/E/Q/S/T/V,M230L)]or [at least 4 mutations of (A98G,K101E/Q,V106I,V108I,V179D)][2 or 3 mutations of (A98G,K101E/Q,V106I,V108I,V179D)]

delavirdine[at least 1 mutation of(L100I,K103H/N/T,V106A/M,Y181C/I,Y188L,G190E,M230L,P236L)]or [at least 2 mutations of (K103S,Y188C/H,G190Q)]or [1 mutation of (K103S,Y188C/H,G190Q) and at least 2 mutations of (A98G,K101E/Q,
V106I,V108I,V179D)]or [at least 4 mutations of (A98G,K101E/Q,V106I,V108I,V179D)][1 mutation of (K103S,Y188C/H,G190Q)]or [2 or 3 mutations of (A98G,K101E/Q,V106I,V108I,V179D)]

NtRTI
tenofovir

NNRTI

Rega v6.3 - 2

efavirenzPI[at least 1 mutation of (K103H/N,V106M,Y188L,G190C/E/Q/S/T/V,M230L)]or [at least 2 mutations of (L100I, K103S/T,V106A,Y181C/I,Y188C/H,G190A,P225H)]or [1 mutation of (L100I,K103S/T,V106A,Y181C/I,Y188C/H,G190A,P225H) and at least
2 mutations of (A98G,K101E/Q,V106I,V108I,V179D)]or [at least 4 mutations of (A98G,K101E/Q,V106I,V108I,V179D)][1 mutation of (L100I,K103S/T,V106A,Y181C/I,Y188C/H,G190A,P225H)]or [2 or 3 mutations of (A98G,K101E/Q,V106I,V108I,V179D)]

esaquinavir{(G48V and L90M) and [at least 2 mutations of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,A71I/T/V,G73S,V82A/F/S/T,I84V)]}or {[at least 1 mutation of (G48V,L90M)] and [at least 3 mutations of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,A71I/T/V,G73S,V82A/F/S/T,I84V)]}or [at least 6 mutations of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,A71I/T/V,G73S,V82A/F/S/T,I84V)](G48V and L90M)
or {[at least 1 mutation of (G48V,L90M)] and [at least 1 mutation of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,A71I/T/V,G73S,V82A/F/S/T,I84V)]}or [at least 4 mutations of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,A71I/T/V,G73S,V82A/F/S/T,I84V)]

ritonavir[at least 2 mutations of (M46I/L,V82A/F/S/T,I84V)]
or {[at least 1 mutation of (M46I/L,V82A/F/S/T,I84V)] and [at least 1 mutation of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S,L90M)]}or [at least 4 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S, L90M)][1 mutation of (M46I/L,V82A/F/S/T,I84V)]or [3 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S,L90M)]

indinavir{(M46I/L and V82A/F/S/T and I84V) and [at least 1 mutation of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S,L90M)]}or {[at least 2 mutations of (M46I/L,V82A/F/S/T,I84V)] and [at least 2 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S,L90M)]}or {[at least 1 mutation of (M46I/L,V82A/F/S/T,I84V)] and [at least 3 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S,L90M)]}or [at least 6 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S, L90M)][at least 2 mutations of (M46I/L,V82A/F/S/T,I84V)]
or {[at least 1 mutation of (M46I/L,V82A/F/S/T,I84V)] and [at least 1 mutation of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S,L90M)]}or [at least 4 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,A71I/T/V,G73S,N88S, L90M)]

nelfinavir[at least 2 mutations of (D30N,V82A,L90M)]
or {[at least 1 mutation of (D30N,V82A,L90M)] and [at least 1 mutation of(M36I,M46I/L,G48V,I54L/V,A71I/T/V,V77I,V82F/S/T,I84V,N88D/S)]}or [at least 4 mutations of(M36I,M46I/L,G48V,I54L/V,A71I/T/V,V77I,V82F/S/T,I84V,N88D/S)][1 mutation of (D30N,V82A,L90M)]or [3 mutations of (M36I,M46I/L,G48V,I54L/V,A71I/T/V,V77I,V82F/S/T,I84V,N88D/S)]

amprenavir{I50V and [at least 3 mutations of(L10F/I/R/V,K20M/R,V32I,L33F,M46I/L,I47V,I54L/M/V,V82A/F/S/T,I84V,L90M)]}or [at least 6 mutations of(L10F/I/R/V,K20M/R,V32I,L33F,M46I/L,I47V,I54L/M/V,V82A/F/S/T,I84V,L90M)]{I50V and [at least 1 mutation of(L10F/I/R/V,K20M/R,V32I,L33F,M46I/L,I47V,I54L/M/V,V82A/F/S/T,I84V,L90M)]}or [at least 4 mutations of(L10F/I/R/V,K20M/R,V32I,L33F,M46I/L,I47V,I54L/M/V,V82A/F/S/T,I84V,L90M)]

(/r)

(/r)

(/r)

Rega v6.3 - 3

lopinavir/r

at least 7 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M46I/L,I47A/V,G48V,I50V,F53L,I54A/L/M/S/T/V,
A71I/L/T/V,G73A/S,V82A/F/S/T,I84V,L90M)

at least 5 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M46I/L,I47A/V,G48V,I50V,F53L,I54A/L/M/S/T/V,
A71I/L/T/V,G73A/S,V82A/F/S/T,I84V,L90M)

atazanavir{I50L and [at least 4 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/M/V,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]}or [at least 6 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/M/V,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]{I50L and [at least 2 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,I54L/V,
A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]}or [at least 4 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]

atazanavir/r{I50L and [at least 6 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/M/V,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,
I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]}or [at least 8 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/M/V,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,
I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]{I50L and [at least 4 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/M/V,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,
I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]}or [at least 6 mutations of(L10F/I/V/Y,K20M/R/T,L24I,V32I,L33F/I/M/V,M36I/L/V,K45N/Q/R,M46I/L/V,G48V,
I54L/V,A71I/T/V,G73A/C/S/T,V77I,V82A/F/M/S/T,I84V,N88D/S,L90M)]

tipranavir/r

at least 4 mutations of (L33F/I/V,V82F/L/T,I84V,L90M)
or at least 3 mutations of (L33F/I/V,V82F/L/T,I84V,L90M) and at least 13 mutations of(L10F/I/R/V/Y,I13V,K20L/M/R/T,L24I/M,D30N,V32I,E34D,M36I/L/V,K45I/R,M46I/L/V,I47
V,G48V,I50V,F53L,I54A/L/M/S/T/V,K55Q/R,A71I/L/T/V,G73A/C/S/T,V77I,V82A/M/S,
N88D/S)at least 3 mutations of (L33F/I/V,V82A/F/L/T,I84V,L90M)

at least 2 mutations of(G36D/E/S/V,V38A/E/M/V,Q40H,N42D/E/K/T,N43D/K/S,L44M,L45M)

1 mutation of (G36D/E/S/V,V38A/E/M/V,Q40H,N42D/E/K/T,N43D/K/S,L44M,L45M)

EI
enfuvirtideaPrimary or key mutations are indicated in bold, secondary or accessory mutations are in plain text.
T69X-XX, X whatever amino acid. ∆67, deletion of amino acid 67. A, alanine; R, arginine; N, asparagine; D, aspartic acid; C, cysteine; Q, glutamine; E, glutamic acid; G, glycine; H, histidine; I, isoleucine; L, leucine; K, lysine;M, methionine; F, phenylalanine; P, proline; S, serine; T, threonine; W, tryptophan; Y, tyrosine and V, valine.
cIf more mutations are present at a certain position (e.g. T215Y and T215F), they are only counted as one mutation in the rules.
dIf none of the criteria to consider an isolate resistant towards a particular drug are full-filled, proceed to the criteria to consider an isolate intermediate resistant. If none of the latter criteria are full-filled, the isolate can be scoredsusceptible to that particular drug.
e/r, PI boosted with baby dose of ritonavir.
NRTI, nucleoside reverse transcriptase inhibitor; NtRTI, nucleotide reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; EI, entry inhibitor.
bRega v6.3 - 4