Aim of this study was to report the 204-week efficacy and safety results of a novel PI- and NRTI-sparing regimen for salvage therapy including maraviroc, raltegravir, etravirine in 28 failing HIV-infected patients with R5-tropic virus. The trend of laboratory parameters was tested by ANOVA for repeated measures and Greenhouse-Geisser probabilities were reported. Results were described as median (Q1-Q3) values. Twenty-six (93%) out of 28 patients completed 204 weeks of treatment. Virological success (HIV-RNA<50 copies/mL) at week 204 was 96%. CD4+ counts significantly increased [244 (158-213) cells/mm3, p<0.0001] from baseline [247 (68-355) cells/mm(3)] as well as CD4+ percentage. Four serious adverse events (1 death due to Hodgkins's lymphoma, 1 anal cancer, 1 Hodgkins's lymphoma, 1 recurrence of mycobacterial spondylodiscitis) were observed; three events led to transitory discontinuation of the antiretroviral therapy due to drug-drug interaction. BMI (p<0.0001) and waist circumference (p<0.0001) significantly increased over 204 weeks. An amelioration was also observed in relation to haemoglobin (p=0.0006), platelets (p<0.0001), white blood cell (p=0.013), neutrophils (p=0.301), lymphocytes (p=0.207) and creatinine (p<0.0001). In highly treatment-experienced patients the maraviroc, raltegravir and etravirine combination is associated with a good long-term efficacy and safety profile.