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Maraviroc (Pfizer's UK-427857, Selzentry or Celsentri outside the US) is the first agent in the new class of oral HIV-1 entry inhibitors to acquire FDA and EMEA approval. It is expected that this drug will be effective only in a subpopulation of HIV-1-infected people, namely those harbouring only the R5 virus. The wide use of this drug is currently hampered by the lack of a readily available R5 virus only determination test (tropism test) and by insufficient scientific insight into the dynamics of R5 and X4 viruses during infection. We discuss the challenges associated with the currently available assay, as well as the potential role of alternative assays.