title: Raltegravir plasma concentrations in treatment-experienced patients receiving salvage regimens based on raltegravir with and without maraviroc coadministration.
abstract: BACKGROUND
  Raltegravir and maraviroc represent new, important resources for HIV-infected patients with intolerance or resistance to other antiretroviral agents. The safety and efficacy of both drugs have been investigated, but there is no information on possible pharmacokinetic interactions between these 2 drugs in clinical practice.
  
  
  OBJECTIVE
  To evaluate raltegravir plasma concentrations in heavily treatment-experienced patients receiving salvage regimens and explore, in a preliminary assessment, the potential influence of maraviroc coadministration and other cofactors on raltegravir trough concentrations (C(trough)).
  
  
  METHODS
  Fifty-four HIV-infected patients with triple class (nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, protease inhibitor) treatment experience starting raltegravir 400 mg twice daily, with (n = 11) or without (n = 43) concomitant maraviroc 300 mg twice daily, were evaluated. All regimens included at least 3 drugs of at least 2 different classes. Raltegravir plasma Ctrough, after at least 1 month of treatment, were analyzed to compare groups of patients taking raltegravir only and raltegravir plus maraviroc. Immunovirological (CD4, HIV-RNA) and clinical data after 6 months of treatment were also collected and described.
  
  
  RESULTS
  Raltegravir plasma Ctrough showed a large variability (range <0.020-2.47 microg/mL). Median levels were similar in the 2 groups (raltegravir + maraviroc 0.104 microg/mL, range 0.025-0.826; raltegravir 0.090 microg/mL, range <0.020-2.47, p = 0.400). Detectable (>0.02 microg/mL) raltegravir concentrations were observed in all patients receiving raltegravir + maraviroc and in 74% of patients receiving raltegravir alone (p = 0.060). After 6 months of treatment, the 2 groups had similar clinical, virologic, and immunologic conditions.
  
  
  CONCLUSIONS
  Coadministration of maraviroc does not seem to have any relevant effects on raltegravir plasma Ctrough in heavily treatment-experienced patients receiving salvage regimens. Further studies should evaluate the potential additional benefits of maraviroc coadministration in terms of virologic and immunologic response.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Liliana E
authors.initials: LE
authors.lastname: Weimer
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.forename: Daniela
authors.initials: D
authors.lastname: Francisci
authors.forename: Chiara
authors.initials: C
authors.lastname: Tommasi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.forename: Roberta
authors.initials: R
authors.lastname: Preziosi
authors.forename: Stefania
authors.initials: S
authors.lastname: Cicalini
authors.forename: Maria
authors.initials: M
authors.lastname: Cusato
authors.forename: Clementina
authors.initials: C
authors.lastname: Galluzzo
authors.forename: Marco
authors.initials: M
authors.lastname: Floridia
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D003510:Cyclohexanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D016879:Salvage Therapy; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D011760:Pyrrolidinones; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc