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

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

Volume: 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

Affiliation:

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

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.

Cite this article as:

Calcagno Andrea, Montrucchio Chiara, Capetti Amedeo, Guaraldi G., Cenderello G., Calza Leonardo, Lanzafame M., Marinaro Letizia, Tettoni M.C., Trentini Laura, D'Avolio Aantonio, Di Perri Giovanni and Bonora Stefano, Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive Patients: Safety, Efficacy and Pharmacokinetics, Current HIV Research 2016; 14 (1) . https://dx.doi.org/10.2174/1570162X13666150929112135