[Conclusions and perspectives. Maraviroc].
This monograph discusses most important aspects Maraviroc, the development and application perspectives of this drug, as well as main questions raised in its use. Maraviroc is the first CCR5 antagonist approved for treating HIV infection. Its imidazopyridine structure interacts with CCR5 and induces a co-receptor conformation that prevents glycoproteins binding to the viral envelope. It has powerful antiviral activity and acts on a wide spectrum of viruses with affinity for this receptor. This situation means that a tropism test has to be done before treatment to define whether the patient is a carrier of R5 variants. Maraviroc is indicated in HIV infected patients who have received previous antiretroviral treatment. It has a low toxicity and, according to preliminary data, a high genetic barrier. The resistance mechanism is associated with changes in the V3 region which allow the virus to recognise the CCR5 co-receptor bound to the Maraviroc molecule. The main cause of treatment failure is the selection of pre-existing X4 strains not detected by the reference test. Maraviroc can be combined with any other antiretroviral on the market or in clinically advanced development. The indication of Maraviroc in the early phases of the infection is not currently recommended and will depend whether it is shown to be inferior when compared other treatments or a benefit in other pathogenic aspects, such as recovery of CD4 lymphocytes or a reduction in viral reservoirs.
Alcamí
José
J
Unidad de Inmunopatología del Sida, Instituto de Salud Carlos III, Madrid, España. ppalcami@isciii.es
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D002986:Clinical Trials as Topic; D003510:Cyclohexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D015686:Gene Products, env / Q000378:metabolism; D006678:HIV / Q000235:genetics / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D000077592:Maraviroc; D008561:Membrane Fusion / Q000187:drug effects*; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D016879:Salvage Therapy; D012641:Selection, Genetic; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053585:Virus Attachment / Q000187:drug effects*; D053586:Virus Internalization / Q000187:drug effects*
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; C527276:CXCR4 protein, human; D003510:Cyclohexanes; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019718:Receptors, CXCR4; D014230:Triazoles; D000077592:Maraviroc