Katholieke Universiteit Leuven
Rega Institute for Medical Research and University Hospitals Leuven
Microbiology and Immunology
Clinical and Epidemiological Virology
Perpetua Gomes4, Kristel Van Laethem1, 2, Anna Maria Geretti3, Ricardo Camacho4 and Anne-Mieke Vandamme1
1 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
2 University Hospitals Leuven, Leuven, Belgium

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

4 Molecular Biology Laboratory, Centro Hospitalar de Liboa Ocidental, Lisbon, Portugal

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

Algorithm for the interpretation of genotypic HIV-2 resistance data
Rega v7.0 © , Leuven, 28 March 2007
Criteria to consider an isolate probably resistant a,b,c

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

NRTI
zidovudine(Q151M and V111l) or (5 mutations of (K70R,Y115F,Q151M,F214L,K223R))

at least 1 mutation of (K70NRS,Q151M, E219D)

didanosine

K65R or (Q151M and V111l) or (5 mutations of (K70R,Y115F,Q151M,F214L,K223R))

at least 1 mutation of (A62V,N69S,M184V,Q151M)

lamivudine

M184V or (Q151M and V111l) or (5 mutations of (K70R,Y115F,Q151M,F214L,K223R))

at least 1 mutation of (K65R,Q151M)

stavudine(Q151M and V111l) or (5 mutations of (K70R,Y115F,Q151M,F214L,K223R))

at least 1 mutation of (K65R,K70NRS,Q151M,E219D)

abacavir(Q151M and V111l) or (5 mutations of (K70R,Y115F,Q151M,F214L,K223R))

at least 1 mutation of (K70N,Q151M,M184V)

NtRTI
tenofovir

K65R or (151M and V111l) or (5 mutations of (K70R,Y115F,Q151M,F214L,K223R))

NNRTI

Not active

nevirapinedelavirdineefavirenz
PIdsaquinavir (/r)

at least 1 mutation of (E63K,T74A,I84V,L90M)

ritonavir(I54M and I82F)

at least 1 mutation of (V47A,I54M,I82F)

indinavir (/r)(I54M and I82F) or V47A

at least 1 mutation of (I54M,V62A,V71I,I82FM,I84V,L99F)

nelfinavir(I54M and I82F)

at least 1 mutation of (I54LM,V62A,V71I,I82F,L90M,L99F)

amprenavir (/r)

Not active

lopinavir/rV47A or (V62A and L99F) or at least 2 mutations of (I50V, I54M, I82LF)

at least 1 mutation of (G48A,I50V,I54M,I64V,I82LF)

atazanavir/r

I50L or (I54M and I82F)

1 mutation of (I54M,I82F)

tipranavir/r(I82F and I54M) or I82L

at least 1 mutation of (I82F,I54M)
Rega v7.0 © - 1

EI
enfuvirtide

Not active

a 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. b If more mutations are present at a certain position (e.g. T215Y and T215F), 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 to consider 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. 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 (e.g., T215 revertants) 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 (e.g., M184IV and TAMs). 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 - NtRTI
PI
PI/rprobably resistant000

possibly resistant
0.5
0.5
0.75

probably susceptible
11
1.5

Target GSS for the entire treatment combination regimen are proposed for therapy-naive persons with indications of transmitted drug resistance (≥3.5), therapy-naive and therapy-experienced persons (≥3), and therapy-experienced persons with limited treatment
options (≥2).

Rega v7.0 © - 2