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European Panel Recommends Either Geno (g2p)
or Pheno (ESTA) for Tropism Testing
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
"for practical reasons genotypic population sequencing is the preferred method in Europe."
Mark Mascolini
A panel of European experts on HIV genotyping, viral coreceptor use (tropism), and antiretroviral therapy recommends either phenotypic testing (with Monogram's ESTA assay) or a genotypic approach (with geno2pheno interpretation) to predict HIV tropism in antiretroviral-naive or experienced people [1]. Although the panel does not state a preference for one tropism approach over the other, it says "it is anticipated that genotypic testing will be used more frequently because of its greater accessibility, lower cost and shorter turnaround time."
The 60-member panel reviewed online citations and hand-searched further publications and conference reports to identify 712 potential articles and 1240 abstracts of interest. After reviewing all these sources, the panel focused on 57 articles and 42 abstracts to guide them in forging a consensus on HIV tropism testing. The panel defined consensus as agreement of more than 75% of panel members. They ranked recommendations as (A) strong, (B) moderate, or (C) optional, based on (I) one or more randomized trials with clinical outcomes and/or validated laboratory endpoints, (II) one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes, and (III) expert opinion.
The new advice goes behind the current recommendation to assess viral tropism before prescribing a CCR5 antagonist. These European leaders call for tropism testing in three groups: (1) antiretroviral-naive people "in whom toxicity or limited therapeutic options are foreseen" (CIII), (2) patients experiencing virologic failure if a CCR5 antagonist is considered (AII) or to give optimal insights into future therapeutic options (BII), or (3) patients experiencing toxicity if a CCR5 antagonist can be of added value (CIII) or if a CCR5 antagonist is considered (AII).
For people with a viral load at or above 1000 copies, the European experts recommend using either the enhanced Trofile assay (ESTA) (BII) or genotypic population sequencing of the V3 loop (BII). For patients with a lower viral load, the panel gives the nod to population genotypic tropism testing (CIII). And if the viral load is below 50 copies or the local amplification threshold, the experts recommend population genotypic testing on proviral DNA (CIII).
If clinicians take the genotypic route, the panel advises triplicate PCR amplification and sequencing with the g2p clonal model interpretation tool with a false-positive rate cutoff of 10%. (The false-positive rate is the probability of classifying R5 virus falsely as X4.) When a low viral load makes amplification unreliable, the panel says proviral DNA may be used, again with triplicate testing at a false-positive rate of 10%. If genotypic DNA testing is not done in triplicate, these experts advise upping the false-positive rate to 20%.
Although both phenotyping and well-conducted genotyping are appropriate for tropism testing, the panel concurs, "for practical reasons genotypic population sequencing is the preferred method in Europe." The panel maintains that tropism test results should be available at the same time as resistance results because delays may exclude use of a CCR5 antagonist or lead to accumulating resistance if a treatment change is postponed.
Among the opinion leaders on the guideline panel are Charles Boucher, Francoise Brun-Vezinet, Bonaventura Clotet, Andrea De Luca, Carlo Perno, Jonathan Schapiro, Vincent Soriano, and Annemarie Wensing, who presented the group's advice.
Reference
1. Vandekerckhove LPR, Wensing AMJ, Kaiser R, et al. Consensus statement of the European guidelines on clinical management of HIV-1 tropism testing. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract O121.
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