Transcript Document

European guidelines on the clinical
management of HIV-1 tropism testing
Vandekerckhove LPR*, Wensing AMJ*, Kaiser R, Brun-Vézinet F, Clotet B, De Luca A, Dressler S, Garcia F, Geretti AM, Klimkait T,
Korn K, Masquelier B, Perno CF, Schapiro JM, Soriano V, Sönnerborg AM, Vandamme AM, Verhofstede C, Walter H , Zazzi M and
Boucher CAB on behalf of the European Consensus Group on clinical management of tropism testing
*These authors contributed equally to these guidelines.
Introduction
CCR5-antagonists such as maraviroc (MVC) specifically inhibit
the entry into host cells and subsequent replication of CCR5tropic HIV variants (R5) by an allosteric mechanism after
binding to the transmembrane CCR5-co-receptor cavity. The
European Medicine Agency (EMA) has approved MVC for use
in treatment-experienced adults in whom only CCR5-tropic
virus is detected. The US Food and Drug Administration (FDA)
but not the EMA has also approved MVC for use in treatment
naïve R5-only individuals.
Recommendations from the European guidelines on Clinical
Management of HIV-1 Tropism Testing
Pre-assessment of viral tropism is required for clinical use of
the drug. In the registration trials the original Trofile-assay
(OTA, Monogram Biosciences) was used for this purpose.
Today, an enhanced version of the Trofile assay (ESTA) with
improved sensitivity for the detection of HIV variants capable of
using the CXCR4 receptor (X4) has replaced the OTA. In
addition, several other phenotypic and genotypic approaches
for tropism determination have been developed by academic
groups and diagnostic companies.
As the number of tropism evaluation methods is growing,
guidelines for optimal use of these methods and their
interpretation are required. This poster summarises the
consensus statement of the European guidelines group on
clinical management of tropism testing. The recommendations
of the panel comprise clinical indications for tropism testing,
selection of the appropriate tropism determination method and
adequate interpretation of results using these methods.
Summary
HIV tropism testing is required to select patients who will
benefit from antiretroviral agents targeting the CCR5 coreceptor.
To date, in most European countries HIV tropism has been
determined using a phenotypic tropism test. The European
guidelines on the clinical management of HIV-1 tropism testing
provide evidence-based recommendations for the clinical use
of tropism testing and expert guidance on unresolved issues
and current developments.
Current data support both the use of V3 genotypic population
sequencing and the commercially available ESTA for coreceptor tropism determination. For practical reasons
genotypic population sequencing is the preferred method in
Europe.
Panel
Albert Jan (Sweden), Alexiev Ivailo (Bulgaria), Åsjö Birgitta (Norway), Balotta Claudia
(Italy), Beshkov Danail (Bulgaria), Boucher Charles (the Netherlands), Braun Patrick
(Germany), Brun-Vézinet Françoise (France), Camacho Ricardo (Portugal), Cane Pat
(UK), Clotet Bonaventura (Spain), Coughlan Suzie (Ireland), Daeumer Martin
(Germany), De Luca Andrea (Italy), Dressler Stephan (European AIDS Treatment
Group), Ene Luminita (Romania), Garcia Federico (Spain), de Gascun Cillian
(Ireland), Geretti Anna Maria (UK), Griskevicius Algirdas (Lithuania), Grossman
Zehava (Israel), Horban Andrzej (Poland), Kaiser Rolf (Germany), Klimkait Thomas
(Switserland), Kolupajeva Tatjana (Latvia), Korn Klaus (Germany), Kostrikis Leon
(Cyprus), Liitsola Kirsi (Finland), Linka Marek (Czech Republic), Zidovec Lepej
Snjezana (Croatia), Masquelier Bernard (France), Minarovits Janos (Hungary),
Nielsen Claus (Denmark), Obermeier Martin (Germany), Otelea Dan (Romania),
Paraskevis Dimitrios (Greece), Paredes Roger (Spain), Perno Carlo Federico (Italy),
Pillay Deenan (UK), Poljak Mario (Slovenia), Poveda, Eva (Spain), PuchhammerStöckl Elisabeth (Austria), Rusconi Stefano (Italy), Schapiro Jonathan (Israel), Schmit
Jean-Claude (Luxembourg), Schuurman Rob (Netherlands), Soriano Vincent (Spain),
Sönnerborg Anders (Sweden), Stanékova Danica (Slovakia), Stanojevic Maja
(Serbia), Svicher Valentina (Italy), Vandamme Anne-Mieke (Belgium),
Vandekerckhove Linos (Belgium), Van Laethem Kristel (Belgium), Verhofstede Chris
(Belgium), Walter Hauke (Germany), Wensing Annemarie (the Netherlands), Yerly
Sabine (Suisse), Zazzi Maurizio (Italy), Zilmer Kai (Estonia)
The Tropism guidelines are available as epublication on the website of The Lancet Infectious Diseases.
These guidelines are an initiative of the EuropeHIVResistance network, EC contract number: LSHPCT-2006-518211, which has now evolved into the European Society for Antiviral Resistance (ESAR).
For more information please send an e-mail to [email protected].