title: Virological response after short-term CCR5 antagonist exposure in HIV-infected patients: frequency of subjects with virological response and associated factors.
abstract: The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log(10) HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4(+) T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4(+) T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains.
authors.affiliation: Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Service of Infectious Diseases, Virgen del Rocío University Hospital, Seville, Lab. 211, Planta 2, Avd. Manuel Siurot s/n, 41013 Seville, Spain. ezequiel.ruizmateos@gmail.com
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.forename: Alejandro
authors.initials: A
authors.lastname: González-Serna
authors.forename: Miguel
authors.initials: M
authors.lastname: Genebat
authors.forename: Kawthar
authors.initials: K
authors.lastname: Machmach
authors.forename: Francesc
authors.initials: F
authors.lastname: Vidal
authors.forename: Angeles
authors.initials: A
authors.lastname: Muñoz-Fernández
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martinez
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D003510:Cyclohexanes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019718:Receptors, CXCR4 / Q000097:blood; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; C527276:CXCR4 protein, human; D003510:Cyclohexanes; D012367:RNA, Viral; D019718:Receptors, CXCR4; D014230:Triazoles; D000077592:Maraviroc