Tropism switch in patients infected with HIV-1 and its clinical implications for the treatment with CCR5-receptor inhibitors.
CCR5 receptor inhibitors are currently being introduced into clinical practice. In some instances treatment failure is related to the selection of pre-existing CXCR4-tropic minority virus strains. Up to date it is unclear whether the outgrowth of a CXCR4 using reservoir is associated with accelerated HIV-disease. In any case, treatment with CCR5 inhibitors should only be initiated in the absence of a relevant CXCR4-tropic minority. Otherwise treatment failure and the accumulation of mutations may ensue. Tropism tests, clinical data and other laboratory parameters help to determine the risk for an individual patient to harbour CXCR4 tropic virus strains, although the negative predictive value of each of these parameters and tests is quite low. If treatment fails re-assessment of viral tropism can help to differentiate between failure due to the development of CCR5 inhibitor resistance or the selection of CXCR4-tropic virus strains. This article presents and discusses available data on viral tropism and tropism testing in the context of CCR5 inhibitor treatment.
Arastéh
Keikawus
K
Vivantes Auguste-Viktoria-Klinikum, Klinik für Innere Medizin, Infektiologie/Gastroenterologie, Rubensstr. 125, 12157 Berlin, Germany. keikawus.arasteh@vivantes.de
Stocker
Hartmut
H
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D019713:Receptors, CCR5 / Q000032:analysis / Q000502:physiology; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000502:physiology
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D019713:Receptors, CCR5; D019718:Receptors, CXCR4