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Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive Patients: Safety, Efficacy and Pharmacokinetics

[ Vol. 14 , Issue. 1 ]

Author(s):

Andrea Calcagno, Chiara Montrucchio, Amedeo Capetti, G. Guaraldi, G. Cenderello, Leonardo Calza, M. Lanzafame, Letizia Marinaro, M.C. Tettoni, Laura Trentini, Aantonio D'Avolio, Giovanni Di Perri and Stefano Bonora   Pages 54 - 60 ( 7 )

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.

Conclusion: 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.

Keywords:

Antiretroviral therapy, nevirapine, NRTIs-sparing, pharmacokinetics, raltegravir.

Affiliation:

Clinica Univesitaria di Malattie Infettive, Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy.

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