Testing for HIV tropism (ie, the ability for different HIV variants to enter cells by binding to a receptor) has become an important step for clinical treatment. Genotypic and phenotypic methods for determining tropism are proliferating. This Review in The Lancet Infectious Diseases presents much-needed guidelines from the European Consensus Group on the clinical management of tropism testing. Tropism testing is required before initiation of maraviroc, the first CCR5 co-receptor antagonist for the treatment of HIV-1 infection that has been approved by the European Medicines Agency (EMA).1
The panel recommends HIV-tropism testing for drug-naive patients in whom toxic side-effects from treatment are expected (eg, those with liver cirrhosis or neuropsychological abnormalities); patients who have poor tolerability to or toxic effects from current treatment or who have central nervous system pathology; and patients who might need a change in treatment.
The guidelines, which were the result of input from 60 panellists from 31 European countries, will be presented at the 9th European Workshop on HIV & Hepatitis in Paphos, Cyprus, this month.
The Review assesses the different genotypic and phenotypic tests for tropism and highlights any disadvantages that the tests carry. The authors point out that: "None of the available tropism assays have been validated in prospective, randomised, double-blind clinical trials with the performance as a primary endpoint." In the absence of a gold standard test, the guidelines recommend the phenotypic enhanced sensitivity Trofile assay or V3 loop2 genotypic sequencing, with a preference for V3 testing because it is more widely available and has a faster turnaround time.
The authors say: "After the EMA approval of maraviroc, the first CCR5 co- receptor antagonist for the treatment of HIV-1 infection, tropism testing is needed for clinical practice."
They add: "Current data lend support to both the use of population genotyping and the commercially available enhanced sensitivity Trofile assay for establishing co-receptor tropism. For practical reasons, genotypic population sequencing is the preferred method in Europe."
The guidelines were an initiative of Prof Charles A Boucher, Dr L P R Vandekerckhove (University of Ghent), and Dr A M J Wensing (University Medical Center Utrecht) in collaboration with the European Society for Antiviral Resistance.
Professor Charles A B Boucher, Department of Virology, Erasmus Medical Centre, Rotterdam, Netherlands. T) +31 651203640. E) info@esar-society.eu
Notes to editors:
1 The chemokine receptors CCR5 and CXCR4 have a key role in the ability of the HIV-1 virus to attach to host CD4 cells. Some HIV variants bind to CCR5, some to CXCR4, and some to both.
2 The V3 loop is a segment of the HIV-1 envelope protein that has a role in determining cell tropism
The Lancet Infectious Diseases