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.