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 HIV and Hepatitis.com Coverage of the
5
th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009)
 July 19 - 22, 2009, Cape Town, South Africa
 The material posted on HIV and Hepatitis.com about IAS 2009 is not approved by nor is it a part of IAS 2009.
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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