Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies.
BACKGROUND
The MOTIVATE-1 and 2 studies compared maraviroc (MVC) along with optimized background therapy (OBT) vs. placebo along with OBT in treatment-experienced patients screened as having R5-HIV (original Monogram Trofile). A subset screened with non-R5 HIV were treated with MVC or placebo along with OBT in a sister safety trial, A4001029. This analysis retrospectively examined the performance of population-based sequence analysis of HIV-1 env V3-loop to predict coreceptor tropism.


METHODS
Triplicate V3-loop sequences were generated using stored screening plasma samples and data was processed using custom software ('ReCall'), blinded to clinical response. Tropism was inferred using geno2pheno ('g2p'; 5% false positive rate). Primary outcomes were viral load changes after starting maraviroc; and concordance with prior screening Trofile results.


RESULTS
Genotype and Trofile results were available for 1164 individuals with virological outcome data (N = 169 non-R5 by Trofile). Compared with Trofile, V3 genotyping had a specificity of 92.6% and a sensitivity of 67.4% for detecting non-R5 virus. However, when compared with clinical outcome, virological responses were consistently similar between Trofile and V3 genotype at weeks 8 and 24 following the initiation of therapy for patients categorized as R5.


CONCLUSIONS
Despite differences in sensitivity for predicting non-R5 HIV, week 8 and 24 week virological responses were similar in this treatment-experienced population. These findings suggest the potential utility of V3 genotyping as an accessible assay to select patients who may benefit from maraviroc treatment. Optimization of the predictive tropism algorithm may lead to further improvement in the clinical utility of HIV genotypic tropism assays.
McGovern
Rachel A
RA
BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Thielen
Alexander
A
Mo
Theresa
T
Dong
Winnie
W
Woods
Conan K
CK
Chapman
Douglass
D
Lewis
Marilyn
M
James
Ian
I
Heera
Jayvant
J
Valdez
Hernan
H
Harrigan
P Richard
PR
D000328:Adult; D018791:CD4 Lymphocyte Count; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000502:physiology; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D000077592:Maraviroc; D012367:RNA, Viral / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014230:Triazoles / Q000008:administration & dosage*; D019562:Viral Load; D056189:Viral Tropism / Q000235:genetics* / Q000502:physiology
D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D015728:Receptors, HIV; D014230:Triazoles; D000077592:Maraviroc