Discordances between interpretation algorithms for genotypic resistance to protease and reverse transcriptase inhibitors of human immunodeficiency virus are subtype dependent.
The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In therapy-experienced patients, subtype G displayed a lot of discordances for saquinavir and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F had more discordance for nelfinavir attributable to the presence of PRO 88S and 82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more discordances than subtype B due to the presence of RT mutational patterns 65R + 115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed well on the level of resistance scored, but some of the discordances could be attributed to specific (subtype-dependent) combinations of mutations. It is not yet known whether therapy response is subtype dependent, but the advice given to clinicians based on a genotypic interpretation algorithm differs according to the subtype.
Snoeck
Joke
J
Rega Institute for Medical Research, Minderbroedersstraat 10, 3000 Leuven, Belgium.
Kantor
Rami
R
Shafer
Robert W
RW
Van Laethem
Kristel
K
Deforche
Koen
K
Carvalho
Ana Patricia
AP
Wynhoven
Brian
B
Soares
Marcelo A
MA
Cane
Patricia
P
Clarke
John
J
Pillay
Candice
C
Sirivichayakul
Sunee
S
Ariyoshi
Koya
K
Holguin
Africa
A
Rudich
Hagit
H
Rodrigues
Rosangela
R
Bouzas
Maria Belen
MB
Brun-Vézinet
Françoise
F
Reid
Caroline
C
Cahn
Pedro
P
Brigido
Luis Fernando
LF
Grossman
Zehava
Z
Soriano
Vincent
V
Sugiura
Wataru
W
Phanuphak
Praphan
P
Morris
Lynn
L
Weber
Jonathan
J
Pillay
Deenan
D
Tanuri
Amilcar
A
Harrigan
Richard P
RP
Camacho
Ricardo
R
Schapiro
Jonathan M
JM
Katzenstein
David
D
Vandamme
Anne-Mieke
AM
D000465:Algorithms; D024882:Drug Resistance, Viral; D005838:Genotype; D006678:HIV / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors