Genotypic
Testing Predicts Response to Maraviroc (Selzentry) as well as Viral Tropism Testing
 | Individuals
determined to have CCR5-tropic HIV using a genotypic test were equally likely
to respond to maraviroc (Selzentry) as those identified using the standard Trofile
viral tropism assay, researchers reported at the 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last month
in Cape Town, South Africa. |
By
Liz Highleyman  Various
strains of HIV use 1 of 2 co-receptors -- CCR5 or CXCR4 -- along with the CD4
receptor to enter human cells. Some HIV can use both co-receptors, and some individuals
have a mix of strains (known as dual/mixed-tropic virus).
Only
patients with exclusively CCR5-tropic HIV are considered eligible to use the CCR5
antagonist maraviroc, which blocks the virus from using this co-receptor. People
considering the drug are screened using a phenotypic viral tropism assay called
Trofile. As the MERIT study demonstrated, accurate
identification of patients with CCR5-tropic virus is an important predictor of
treatment response. Now,
researchers have shown that a genotypic tropism test may perform equally well
in predicting which patients will respond to maraviroc and other drugs in its
class. Genotypic tests (which look at viral genetic sequences) are easier to do
than phenotypic tests (which look at how the virus behaves in a test tube), and
therefore are typically less expensive.
Investigators retrospectively analyzed
stored samples from a subset of 572 participants in the MOTIVATE-1
trial, which evaluated maraviroc vs placebo, combined with an optimized background
regimen, in treatment-experienced patients. They compared treatment response rates
between patients identified as having CCR5 virus according to the genotypic test
and the Trofile assay. Note that this study used the original Trofile test, not
the enhanced sensitivity assay used in the MERIT-ES
re-analyis.
The genotypic test looked at the V3 loop of the HIV-1 gp120
protein, which plays a role in interactions between the viral envelope and host
cell co-receptors. The researchers compared 2 algorithms, "Geno2pheno"
(g2p) and PSSM. Results  | Virological
response was similar regardless of whether tropism was determined using the genotypic
test or the standard Trofile assay. | | At
8 weeks, similar proportions of patients identified using the genotypic test with
the g2P algorithm or Trofile achieved undetectable viral load (71.9% vs 71.6%,
respectively). | | Virological
response rates were also similar at 24 weeks (46.1% vs 46.4%, respectively). | | Compared
with Trofile, the genotypic test had sensitivities for detecting non-CCR5-tropic
virus of 63% and 56% using the g2p and PSSM algorithms, respectively. | | Corresponding
specificities were 91% and 90%, respectively. | | Triplicate
sequencing resulted in a change in tropism determination from CCR5-tropic to non-CCR5-tropic
in about 7.5% of patient blood samples. |
"V3
genotype and standard Trofile were comparable in predicting antiviral responses
to maraviroc in treatment experienced patients," the researchers concluded.
"V3 genotype is an attractive option for tropism screening." "Despite
apparently poor sensitivity of standard genotyping for predicting non-[CCR5] HIV
relative to standard Trofile," they added, these findings "[suggest]
the potential of genotyping as an accessible assay to select candidates for maraviroc." "HIV
V3 genotyping shows promise as a significantly faster and more cost-effective
way to correctly identify patients who would benefit from CCR5 antagonists like
maraviroc," said lead investigator Richard Harrigan in a press release issued
by the B.C. Centre for Excellence in HIV/AIDS in Vancouver. "Since the genotypic
test is based on methods that are already widely used through the same labs that
provide HIV drug resistance testing, this approach could become broadly available
and conducted at the same time as resistance testing to determine susceptibility
to all drugs, including maraviroc." BC
Centre for Excellence in HIV/AIDS, Vancouver, Canada; Max-Planck Institute for
Informatics, Saarbrucken, Germany; Fortinbras Research, Buford, GA; Pfizer, Inc.,
New York, NY; Pfizer R&D, Sandwich, UK; Pfizer R&D, New London, CT. 8/4/09 Reference
PR
Harrigan, R McGovern, W Dong, and others. Screening for HIV tropism using population-based
V3 genotypic analysis: a retrospective virological outcome analysis using stored
plasma screening samples from MOTIVATE-1. 5th International AIDS Society Conference
on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape
Town, South Africa. Abstract
WeLBA101. Other
source
British
Columbia Centre for Excellence In HIV/AIDS.
Genetic Test Predicts Response
to Maraviroc in Treatment-Experienced HIV Patients. Press release. July
22, 2009.
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