Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.
Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.
Laboratoire de Virologie, CHU de Bordeaux, Bordeaux Cedex, France.
Patricia
P
Recordon-Pinson
Cathia
C
Soulié
Philippe
P
Flandre
Diane
D
Descamps
Mouna
M
Lazrek
Charlotte
C
Charpentier
Brigitte
B
Montes
Mary-Anne
MA
Trabaud
Jacqueline
J
Cottalorda
Véronique
V
Schneider
Laurence
L
Morand-Joubert
Catherine
C
Tamalet
Delphine
D
Desbois
Muriel
M
Macé
Virginie
V
Ferré
Astrid
A
Vabret
Annick
A
Ruffault
Coralie
C
Pallier
Stéphanie
S
Raymond
Jacques
J
Izopet
Jacques
J
Reynes
Anne-Geneviève
AG
Marcelin
Bernard
B
Masquelier
D000328:Adult; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*; D018523:Tropism
D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D019713:Receptors, CCR5; D015728:Receptors, HIV; D014230:Triazoles; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D000077592:Maraviroc