Treatment of multi-drug experienced patients is an important concern in the management of HIV-1 disease, partially solved by the availability of new drugs acting at different phases of viral replication. Immune recovery during cART is linked both to the activity of antiviral drugs, as well as to the regenerative capability of thymus and bone marrow. We report a patient with a 22-year-old HIV-1 disease and an AIDS diagnosis for 15 years, with extensive resistance to all antiretroviral drugs, who never had treatment interruption, except for short spells due to adverse effects. This decision was supported by both findings elsewhere that interruptions of cART in experienced patients with advanced disease are strongly associated with more rapid disease progression and by our evaluation of his bone marrow activity. The colony-forming cells assay performed in the patient showed residual clonogenic capability, increased in vitro by addition of protease inhibitors and IL-2. A new therapeutic scheme including darunavir and maraviroc allowed dramatic changes leading both to a quick reduction in plasmatic viral load with an impressive immune reconstitution and an improvement in clinical conditions.