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 v6.1, October 2, 2003
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,T215F/Y,K219E/Q) andnot M184I/V]
or [at least 2 mutations of (M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/Q) andM184I/V and G333D/E]
or [at least 3 mutations of (M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/Q) andM184I/V][1 mutation of (M41L,D67N,T69A/N,K70R,L210W,K219E/Q) and not M184I/V]
or [1 mutation of (M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/Q) and M184I/V
and G333D/E]
or [2 mutations of (M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/Q) 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/Q)]

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/Q)]

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 2 mutations of(M41L,D67N,T69A/N,K70R,L210W,T215F/Y,K219E/Q)]}

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,T215F/Y,K219E/Q)]

3 mutations of (M41L,D67N,T69A/D/N,K70R,L210W,T215F/Y,K219E/Q)

Rega v6.1 - 1

abacavir[at least 1 mutation of (∆67,T69G)]or [at least 2 mutations of (K65R,T69X-XX,L74V,Y115F,Q151M,M184I/V,T215F/Y)]or {[at least 1 mutation of (K65R,T69X-XX,L74V,Y115F,Q151M,M184I/V)] and [at least
3 mutations of (M41L,E44A/D,D67N,T69A/D/N,K70R,V75T,V118I,L210W,K219E/Q)]}or [at least 6 mutations of(M41L,E44A/D,D67N,T69A/D/N,K70R,V75T,V118I,L210W,T215F/Y,K219E/Q)][at least 4 mutations of(M41L,E44A/D,D67N,T69A/D/N,K70R,V75T,V118I,L210W,T215F/Y,K219E/Q)]or (M41L and T215F/Y)
or [1 mutation of (K65R,T69X-XX,L74V,Y115F,Q151M,M184I/V)][at least 1 mutation of (K65R,T69X-XX)][at least 1 mutation of (L74V,Q151M)]
or [M41L and at least 2 mutations of (D67N,K70R,L210W,T215Y/F,K219E/N/Q)]
or [L210W and at least 2 mutations of (M41L,D67N,K70R,T215Y/F,K219E/N/Q)]
or [T215Y/F and at least 2 mutations of (M41L,D67N,K70R,L210W,K219E/N/Q)]

nevirapine[at least 1 mutation of (L100I,K103N,V106A,Y181C/I,Y188C/H/L,G190A/E/S,M230L)]or [at least 2 mutations of (A98G,K101E/Q,V106I,V108I,V179D)]

1 mutation of (A98G,K101E/Q,V106I,V108I,V179D)

delavirdine[at least 1 mutation of (L100I,K103N,V106A,Y181C/I,Y188L,G190E,M230L,P236L)]or [at least 2 mutations of (A98G,K101E/Q,V106I,V108I,V179D,Y188C/H)]

1 mutation of (A98G,K101E/Q,V106I,V108I,V179D,Y188C/H)

efavirenz[at least 1 mutation of (K103N,Y188L,G190S,M230L)]or [at least 2 mutations of(L100I,K101E/Q,V106A/I,V108I,V179D,Y181C/I,Y188C/H,G190A/E/T,P225H)]

1 mutation of(A98G,L100I,K101E/Q,V106A/I,V108I,V179D,Y181C/I,Y188C/H,G190A/E/T,P225H){(G48V and L90M) and [at least 2 mutations of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,L63P,A71I/T/V,G73S,V82A/F/S/T,I84V)]}or {[1 mutation of (G48V,L90M)] and [at least 3 mutations of(L10F/I/R/V,K20M/R,M46I/L,I54L/V,L63P,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,L63P,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,L63P,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,L63P,A71I/T/V,G73S,V82A/F/S/T,I84V)][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,L63P,A71I/T/V,G73S,N88S,L90M)]}or [at least 4 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,L63P,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,L63P,A71I/T/V,G73S,N88S,L90M)]

NtRTI
tenofovir

NNRTI

PIesaquinavir(/r)

ritonavir

Rega v6.1 - 2

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,L63P,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,L63P,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,L63P,A71I/T/V,G73S,N88S,L90M)]}or [at least 6 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,L63P,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,L63P,A71I/T/V,G73S,N88S,L90M)]}or [at least 4 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V,L63P,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,L63P,A71I/T/V,V77I,V82F/S/T,I84V,N88D/S)]}or [at least 4 mutations of(M36I,M46I/L,G48V,I54L/V,L63P,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,L63P,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,L63P,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,L63P,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,L63P,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,L63P,V82A/F/S/T,I84V,L90M)]

lopinavir/r

at least 6 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M46I/L,I47V,G48V,I50V,F53L,I54A/L/M/S/T/V,L63P,
A71I/L/T/V,V82A/F/S/T,I84V,L90M)

at least 4 mutations of(L10F/I/R/V,K20M/R,L24I,L33F,M46I/L,I47V,G48V,I50V,F53L,I54A/L/M/S/T/V,L63P,
A71I/L/T/V,V82A/F/S/T,I84V,L90M)

atazanavir{(I50L or A71V) and [at least 3 mutations of(L10F/I/Y,K20I/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45R,M46I/L/V,G48V,I54V,L63A/P/T,A71T,G73A/C/S/T,V77I,V82A/M/T,I84V,N88D/S,L89M,L90M)]}or {(I50L and A71V) and [at least 1 mutation of(L10F/I/Y,K20I/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45R,M46I/L/V,G48V,I54V,L63A/P/T,A71T,G73A/C/S/T,V77I,V82A/M/T,I84V,N88D/S,L89M,L90M)]}or [at least 7 mutations of(L10F/I/Y,K20I/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45R,M46I/L/V,G48V,I54V,L63A/P/T,
A71T,G73A/C/S/T,V77I,V82A/M/T,I84V,N88D/S,L89M,L90M)]{(I50L or A71V) and [at least 2 mutations of(L10F/I/Y,K20I/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45R,M46I/L/V,G48V,I54V,L63A/P/T,
A71T,G73A/C/S/T,V77I,V82A/M/T,I84V,N88D/S,L89M,L90M)]}or (I50L and A71V)or [at least 4 mutations of(L10F/I/Y,K20I/R/T,L24I,V32I,L33F/I/MV,M36I/L/V,K45R,M46I/L/V,G48V,I54V,L63A/P/T,
A71T,G73A/C/S/T,V77I,V82A/M/T,I84V,N88D/S,L89M,L90M)]

(/r)

(/r)

Rega v6.1 - 3

EI
enfuvirtide

at least 2 mutations of1 mutation of (G36D/E/S/V,I37V,V38A/E/M/V,Q40H,N42D/E/K/T,N43D/K/S,L44M,L45M)(G36D/E/S/V,I37V,V38A/E/M/V,Q40H,N42D/E/K/T,N43D/K/S,L44M,L45M)
Primary or key mutations are indicated in bold, secondary or accessory mutations are in plain text.
b
T69X-XX, either T69S-SS, T69S-SG, T69S-AG, T69S-SA or T69T-SG. ∆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 fullfilled, the isolate can be scored susceptible 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.
aRega v6.1 - 4