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.
Recordon-Pinson
Patricia
P
Laboratoire de Virologie, CHU de Bordeaux, Bordeaux Cedex, France.
Soulié
Cathia
C
Flandre
Philippe
P
Descamps
Diane
D
Lazrek
Mouna
M
Charpentier
Charlotte
C
Montes
Brigitte
B
Trabaud
Mary-Anne
MA
Cottalorda
Jacqueline
J
Schneider
Véronique
V
Morand-Joubert
Laurence
L
Tamalet
Catherine
C
Desbois
Delphine
D
Macé
Muriel
M
Ferré
Virginie
V
Vabret
Astrid
A
Ruffault
Annick
A
Pallier
Coralie
C
Raymond
Stéphanie
S
Izopet
Jacques
J
Reynes
Jacques
J
Marcelin
Anne-Geneviève
AG
Masquelier
Bernard
B
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