09 March 2001

Rega v5: Algorithm for the use of genotypic resistance data
Kristel Van Laethem and Anne-Mieke Vandamme
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
Criteria to consider an isolate resistant or in the process of developing resistance resulting in the advise against aparticular drug: whenever the following mutations are found either as indicated or in combination with stillother mutations

NRTI

NNRTI

PIdrugAmino acid substitutions

AZT

T215Y/F in absence of M184V/I; or (Q151M or T69X-XX); or 2 of (M41L,D67N,
K70R,L210W,T215Y/F,K219Q/E) in absence of M184V/I or in presence of(M184V/I+G333D/E); or 3 of (M41L,D67N,K70R,L210W,T215Y/F,K219Q/E) inpresence of M184V/I

DDC

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

DDI

1 of (K65R,T69G,T69X-XX,L74V,Q151M)

3TC

M184V/I or (K65R and Q151M)

d4T

1 of (∆67,T69G,T69X-XX,V75A/M/S/T,Q151M) or [4 of(M41L,D67N,T69D/N,K70R,L210W,T215Y/F,K219Q/E)]

ABC∆67 or T69G or [2 of (K65R,T69X-XX,L74V,Y115F, Q151M, M184V/I,T215Y/F)];or [1 of (K65R,T69X-XX,L74V,Y115F, Q151M, M184V/I) and 3 of(M41L,D67N,K70R,V75T, V118I, L210W,T215Y/F,K219Q/E)]

NVP,DLV

1 of [L100I,K103N,V106A/I,V108I,Y181C/I,Y188L,Y188C/H (for NVP),
G190E,G190A/S (for NVP),M230L, P236L (for DLV) ]EFVK103N; or Y188L; or G190S; or M230L; or [2 of (L100I, K101E/Q, V106A, V108I,
V179D, Y181C/I, Y188C/H, G190A/E/T)]

RTV orIND[(M46I/L or V82A/F/T/S or I84V)+1 of (L10F/I/R/V,K20M/R,L24I,L33F,M36I,M46I/L,G48V,I54V/L,L63P,A71I/T/V,G73S,V82A/F/T/S,I84V,N88S,L90M)];or [4 of (L10I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54L/V, L63P,A71I/T/V,G73S,N88S,L90M)]

SQV[(G48V or L90M) + 1 of (L10F/I/R/V, K20M/R,M46I/L,G48V, I54V/L,L63P,
A71I/T/V,G73S, V82A/F/T/S,I84V,L90M)]; or [4 of(L10F/I/R/V,K20M/R,M46I/L,I54V/L, L63P, A71I/T/V,G73S,V82A/F/T/S,I84V)]

NLF[1 of (D30N,L90M,V82A) + 1 of (D30N,M36I,M46I/L,G48V,I54L/V, L63P,
A71I/T/V, V77I,V82A/F/T/S,I84V,N88D/S,L90M)]; or [4 of (M36I,M46I/L,
G48V,I54L/V,L63P,A71I/T/V,V77I,V82F/T/S,I84V,N88D/S)]

APV[I50V + 1 of (L10F/I/R/V,K20M/R,V32I,M46I/L,I47V,I54L/V, L63P, V82A/F/T/S,I84V,L90M)]; or [4 of (L10F/I/R/V,K20M/R, V32I,M46I/L,I47V,
I54L/V,L63P,V82A/F/T/S,I84V,L90M)]

LPV/
RTV

More than 6 of (L10F/I/R/V,K20M/R,L24I,L33F, M46I/L,F53L,I54A/L/V,
L63P,A71I/L/T/V,V82A/F/T/S,I84V,L90M)

BMS23
2632

More than 6 of (L10F/I/Y, K20I/R/T, L24I, V32I, L33F/V/M/I, M36V/I/L, M46L/I/V,
G48V, I50V/L, I54V, L63A/P/T, A71T/V, G73C/A/T, V77I, V82A/M/T, I84V,
N88D/S, L89M, L90M)
Primary or key mutations are indicated in bold, secondary or accessory mutations are in plain text

Criteria to consider an isolate sensitive resulting in no restraint on the use of a particular drug
No mutations or only 1 non-essential PI mutation; for ZDV 1 of(M41L,D67N,K70R,L210W,T215Y/F,K219Q/E) in presence of M184V/I; for d4T up to 2 of
(M41L,D67N,T69D/N,K70R,L210W, T215Y/F,K219Q/E); for ABC up to 3 of
(M41L,D67N,K70R,V75T,V118I,L210W,T215Y/F,K219Q/E); for LPV/RTV up to 4 of
(L10F/I/R/V,K20M/R,L24I,L33F, M46I/L,F53L,I54A/L/V, L63P,A71I/L/T/V,V82A/F/T/S,I84V,L90M);
for BMS232632 up to 3 of (L10F/I/Y, K20I/R/T, L24I, V32I, L33F/V/M/I, M36V/I/L, M46L/I/V, G48V,I50V/L, I54V, L63A/P/T, A71T/V, G73C/A/T, V77I, V82A/M/T, I84V, N88D/S, L89M, L90M)

Criteria to advise against a particular drug when other options are still available
Any number of drug-related mutations as listed in the upper panel which is inbetween sensitive (middlepanel) and resistant (drug-related mutations in upper panel). In addition: for ABC, DDI, and DDC 4 of(M41L, D67N, T69D, K70R, V75T, L210W, T215Y/F, K219Q/E); for DDI and DDC the presence ofM184V/I; for ABC T215Y/F+M41L; for 3TC the presence of E44A/D and/or V118I in combination withseveral AZT resistance mutations, or the presence of ∆67 or T69X-XX; for d4T 3 of (M41L, D67N,T69D/N, K70R, L210W, T215Y/F, K219Q/E); for DDI the presence of V75T; for NNRTIs also A98G; forNVP and DLV K101E/Q or V179D; for DLV Y188C/H
T69X-XX can be either T69S-SS, T69S-SG, T69S-AG , T69S-SA or T69T-SG . ∆67 is the deletion of aminoacid 67. Patients carrying virus with combinations of mutations scored as resistant in the upper panel, may
still be partially responding to Mega-HAART (>4 drugs). Patients carrying virus with combinations ofmutations scored as intermediate in the lower panel, may still be temporarily responding to this drug in aHAART combination.