Katholieke Universiteit Leuven
Rega Institute for Medical Research and University Hospitals Leuven
Microbiology and Immunology
Clinical and Epidemiological Virology
Perpetua Gomes1, Kristel Van Laethem2, 3, Anna Maria Geretti4, Ricardo Camacho1 and Anne-Mieke Vandamme2
1 Molecular Biology Laboratory, Centro Hospitalar de Liboa Ocidental, Lisbon, Portugal

2 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
3 University Hospitals Leuven, Leuven, Belgium

4 Royal Free Hospital and RF&UC College Medical School, London, United Kingdom

www.kuleuven.ac.be/rega/cev/links
kristel.vanlaethem @uz.kuleuven.ac.be

Algorithm for the interpretation of genotypic HIV-2 resistance data
Rega v8.0.1 ©, Leuven, 3 February 2009
The rules include and score mutations for which in vitro phenotypic drug resistance or in vivo therapy response data have been reported, or for which retrospective associations with drug experience have been described. Some of the mutations do not necessarily
result in high-level phenotypic resistance. Instead, they have been identified as key mutations along a pathway leading to high-level resistance or have proved to be predictive of therapy failure. Where supported by reliable evidence, the antagonistic or synergistic
interaction effects of combinations of mutations are also incorporated. Three levels of interpretation criteria are applied: for HIV-2, criteria to consider an isolate probably resistant, possibly resistant and probably susceptible. Some drugs (e.g., enfuvirtide) are scored
as not active against HIV-2, irrespective of the mutations present.
Genotypic susceptibility scores (GSS) are derived from the three susceptibility levels for each drug class or individual drug. Although the same rules apply to each PI and its respective PI/r, different GSS are assigned to the boosted and un-boosted drug.
GSS
NRTI - NtRTIPIPI/r
INI

probably resistant0000

possibly resistant
0.5
0.25
0.75
-probably susceptible
10.75
1.5
1Target GSS for the entire treatment combination regimen are proposed. Resistance development is expected when therapy changes with GSS below the target are installed.
Clinical situation
Therapy-naive persons with indications of transmitted drug resistance
Therapy-naive and therapy-experienced persons
Therapy-experienced persons with limited treatment options

Target GSS≥3.5≥3≥2Criteria to consider an isolate probably resistant a,b,c

Criteria to consider an isolate possibly resistant a,b,c

NRTI
zidovudine(Q151M and V111I) or [at least 5 mutations of (K70R,V111I,Y115F,Q151M,F214L,S215ACFLY,K223R)]

at least 1 mutation of (K70R,Q151M,S215ACFLY)

didanosine

K65R or (Q151M and V111I) or [at least 5 mutations of (A62V,N69ST,K70R,V111I,Y115F,Q151M,F214L,S215ACFLY,K223R)]

at least 1 mutation of (A62V,Q151M)

stavudine(Q151M and V111l) or [at least 5 mutations of (K65R,K70R,V111I,Y115F,Q151M,F214L,S215ACFLY,K223R)]

at least 1 mutation of (K65R,K70R,Q151M,S215ACFLY)

lamivudine

M184IV or [Q151M and at least 1 mutation of (K65R,V111I)]or [at least 5 mutations of (K65R,K70R,V111I,Y115F,Q151M,F214L,S215ACFLY,K223R)]

at least 1 mutation of (K65R,Q151M)

abacavir[Q151M and at least 1 mutation of (K65R,V111I,Y115F,M184IV)]or [at least 5 mutations of (K65R,K70R,V111I,Y115F,Q151M,M184IV,F214L,S215ACFLY,K223R)]
or [M184IV and at least 1 mutation of (K65R,L74IV,Y115F)]

at least 1 mutation of (Q151M,M184IV)

emtricitabine

M184IV or [Q151M and at least 1 mutation of (K65R,V111I)]or [at least 5 mutations of (K65R,K70R,V111I,Y115F,Q151M,F214L,S215ACFLY,K223R)]

at least 1 mutation of (K65R,Q151M)

Rega v8.0.1 © - 1

NtRTI
tenofovir

K65R or (151M and V111I) or [at least 5 mutations of (K70R,V111I,Y115F,Q151M,F214L,S215ACFLY,K223R)]

NNRTI

Not active

nevirapinedelavirdine
efavirenz
PIdsaquinavir (/r)

at least 2 mutations of (G48V,I84V,L90M)[at least 1 mutation of (G48V,I54LM,I82F,I84V,L90M)] or [V71I and L90M]

indinavir (/r)

V47A or I54M or I82F or [at least 2 mutations of (I84LV,L90M,L99F)][at least 1 mutation of (V71I,I84LV,L90M)] or [V62A and L99F]

nelfinavir

I54M or I82F or [V62A and L99F] or [at least 2 mutations of (I54L,I84V,L90M)]

at least 1 mutation of (I54L,V62A,V71I,I84V,L90M,L99F)

amprenavir (/r)

Not activelopinavir/rV47A or I54M or [V62A and L99F] or [at least 2 mutations of (I50V,I82FL)]

at least 1 mutation of (V33I,G48V,I50V,I64V,I82FL)

atazanavir/r

I50L or (I54M and I82F)

at least 1 mutation of (I54M,I82F,L90M)

tipranavir/rI82L or (I54M and I84V)

at least 1 mutation of (I50V,I54M,I82F,I84V)

darunavir/r

at least 2 mutations of (I50V,I54M,64V,82F,84V,89V)

at least 1 mutation of (I50V,I54M,64V,82F,84V)

EI
enfuvirtide

Not active

INI
raltegravir[at least 1 mutation of (148HKR,155HS)]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. b If more mutations are present at a certain position (e.g. K70N and K70R), they are only counted as one mutation in the rules. c If none of the criteria to consider an isolate probably resistant towards a particular drug are full-filled, proceed to the criteria toconsider an isolate possibly resistant. If none of the latter criteria are full-filled, the isolate can be scored probably susceptible to that particular drug. d 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; INI, integrase inhibitor.
aRega v8.0.1 © - 2