Vandekerckhove LPR*, Wensing AMJ*, Kaiser R, Brun-V

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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.
Recommendations from the European guidelines on
Clinical Management of HIV-1 Tropism Testing
Introduction CCR5-antagonists such as maraviroc
(MVC) specifically inhibit the entry into host
cells and subsequent replication of CCR5-tropic
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. 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
co-receptor. 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 co-receptor
tropism determination. For practical reasons
genotypic population sequencing is the preferred
method in Europe.
PanelAlbert 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),
Puchhammer-Stöckl 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
LSHP-CT-2006-518211, which has now evolved into
the European Society for Antiviral Resistance
(ESAR). For more information please send an
e-mail to info_at_esar-society.eu.