title: Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive Patients: Safety, Efficacy and Pharmacokinetics.
abstract: BACKGROUND
  Tolerability, long-term toxicities and selection of resistant variants limit the use and efficacy of antiretroviral drugs in HIV-positive patients. Novel combinations are needed for mantaining long-term control of HIV replication; nevertheless scarse data are available on protease inhibitor-free dual antiretroviral therapies.
  
  
  METHODS
  A multi-centric retrospective study was conducted including HIV-1-positive patients on raltegravir/nevirapine dual regimens. Plasma concentrations were measured as therapeutic drug monitoring while a subset of patients underwent intensive 12-hour pharmacokinetic evaluation.
  
  
  RESULTS
  A total of 77 patients switching from successful regimens (76.6% male, median age 52 years) was included; 10 patients on raltegravir plus nevirapine once-daily while 67 subjects on twice-daily schedule. After a median follow-up of 32 months 69 patients (89.6%) were still successfully on treatment. Three patients discontinued for side effects (skin rash or hepatoxicity). Virological failure was observed in five patients (6.5%, 3 on once-daily schedule): in 4 patients (80%) resistance-associated mutations were observed (4 reverse transcriptase, 2 integrase). Triglycerides decreased in patients switching with lipid abnormalities (n=52) and estimated creatinine clearance increased in those with less than 60 ml/min (n=13). Median trough raltegravir and nevirapine concentrations were 83 ng/ml (32-227) and 5460 ng/ml (4037-7221); intensive 12-hours pharmacokinetic parameters (n=7) were similar to published data.
  
  
  CONCLUSIONS
  Dual therapy with raltegravir/nevirapine in selected patients was highly effective over a 32-month follow up: virological failure was infrequent (6.5%), most common with once-daily schedule (60%) and often associated with the selection of resistance-associated mutations (80%). Twice-daily raltegravir plus nevirapine deserves further clinical evaluation as an NRTI- and PI-sparing strategy in selected patients.
authors.affiliation: Clinica Univesitaria di Malattie Infettive, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy. andrea.calcagno@unito.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcagno
authors.forename: Chiara
authors.initials: C
authors.lastname: Montrucchio
authors.forename: Amedeo
authors.initials: A
authors.lastname: Capetti
authors.forename: G
authors.initials: G
authors.lastname: Guaraldi
authors.forename: G
authors.initials: G
authors.lastname: Cenderello
authors.forename: Leonardo
authors.initials: L
authors.lastname: Calza
authors.forename: M
authors.initials: M
authors.lastname: Lanzafame
authors.forename: Letizia
authors.initials: L
authors.lastname: Marinaro
authors.forename: M C
authors.initials: MC
authors.lastname: Tettoni
authors.forename: Laura
authors.initials: L
authors.lastname: Trentini
authors.forename: Aantonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068898:Raltegravir Potassium / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D000068898:Raltegravir Potassium; D019829:Nevirapine