1 March 2000

Rega v2: Algorithm for the use of genotypic resistance data
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 resistanceresulting in the advise against a particular drug

NRTI

NNRTI

PIdrugAmino acid substitutions

AZT

T215Y/F in absence of M184V; or Q151M; or T69S-SS; or 2 of (M41L, D67N, K70R,
L210W, T215Y/F, K219Q) in absence of M184V or in presence of M184V + G333D/E; or 3of (M41L, D67N, K70R, L210W, T215Y/F, K219Q) in presence of M184V

DDC

K65R; or T69D; or L74V; or V75T; or Q151M

DDIK65R; or T69S-SS; or L74V; or Q151M

3TC

M184V/I; or (K65R and Q151M)

d4T

T69S-SS; or V75A/M/S/T; or Q151M; or [4 of(M41L,D67N,T69D/N,K70R,L210W,T215Y/F,K219Q)]

ABC[2 of (K65R,T69S-SS,L74V,Y115F, Q151M, M184V/I,T215Y/F)]; or [1 of (K65R,T69SSS,L74V,Y115F, Q151M, M184V/I) and 3 of (M41L,D67N ,K70R,V75T, V118I,
L210W,T215Y/F,K219Q)]

PMEA

K65R; or K70E

NVP,DLV

L100I; or K103N; or V106A/I; or V108I; or Y181C/I; or Y188L; or Y188C/H (for NVP) orG190S/A (for NVP); or P236L (for DLV)EFVK103N; or Y188L; or G190S; or [2 of (L100I, K101E/Q, V106A, V108I, V179D, Y181C/I,
Y188C/H, G190A)]

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,A71I/T/V,G73S,V82A/F/T/S,I84V,L90M)]; or [4 of(L10I/R/V,K20M/R,L24I,L33F,M36I,G48V,I54V/L,A71I/T/V,G73S,L90M)]

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

NLF[(D30N or L90M) + 1 of (D30N,M36I,M46I/L,I54V/L,A71I/T/V,
V77I,V82A/F/T/S,I84V,N88D,L90M)]; or [4 of (M36I,M46I/L,I54V/L,A71I/T/V,V77I,V82A/F/T/S,I84V,N88D)]

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

LPV/RT
V

More than 6 of (L10F/I/R/V,K20M/R,L24I,M46I/L,F53L,I54V/L,A71I/T/V,V82A/F/T/S,I84V,L90M)

Primary or key mutations are indicated in bold, secondary or non-essential 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 d4T up to 2 of
(M41L,D67N,T69D/N,K70R,L210W,T215Y/F,K219Q); for ABC up to 3 of
(M41L,D67N,K70R,V75T,V118I,L210W,T215Y/F,K219Q); for ABT-378 up to 4 of
(L10F/I/R/V,K20M/R,L24I,M46I/L,F53L,I54V/L,A71I/T/V,V82A/F/T/S,I84V,L90M)

62

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 (middle panel) andresistant (drug-related mutations in upper panel). In addition: for ABC, DDI, and DDC 4 of (M41L, D67N, T69D,K70R, V75T, L210W, T215Y/F, K219Q); for DDI and DDC the presence of M184V/I; for ABC T215Y/F+M41L; for
3TC the presence of E44A/D and/or V118I in combination with several AZT resistance mutations, or the presence ofT69S-SS; for d4T 3 of (M41L, D67N, T69D/N, K70R, L210W, T215Y/F, K219Q); for DDI the presence of V75T; forZDV T215/Y in presence of M184V/I and in absence of other mutations; for NNRTIs also A98G; for NVP and DLV
K101E/Q; for DLV Y188C/H

Patients carrying virus with combinations of mutations scored as resistant in the upper panel, may still be partially
responding to MegaHAART (>4 drugs). Patients carrying virus with combinations of mutations scored as intermediatein the lower panel, may still be temporarily responding to this drug in a HAART combination.

This algorithm was based on personal experience, on the references described in the legend to Figure 1, andon Anton et al., 1999; Bacheler et al., 1999, Bloor et al., 1999; Condra et al., 1999; Danner et al., 1995; Daveyet al., 1996; De Noon, 1998; Gulick et al., 1996; Hammer et al., 1999; Havlir et al., 1995,1996; Hertogs etal., 2000; Katzenstein et al., 1996; Kemp et al., 1999; Kleim et al., 1997; Staszewski et al., 1997; Lanier etal., 1999; Larder et al., 1991, 1998; Lea et al., 1996; Lin et al., 1999; Markowitz et al., 1995; Patick et al.,
1998; Schinazi et al., 1999; Schmidt et al., 2000; Schuurman et al., 1995; Shafer et al., 1999a; Staszewski etal., 1998; Sun et al., 2000; Tisdale et al., 1999; Vandamme et al., 2000b, Winters et al., 1998.

63