Efficacy and safety of morphological and metabolic alterations treatment in HIV related lipodystrophy syndrome have never been evaluated outside clinical trials and progression of lipodystrophy remains uncertain. This is a 48 weeks follow up observational retrospective study over consecutive patients attending the Metabolic Clinic of the University of Modena and Reggio Emilia in whom a biochemical, antropometric with DEXA and psychometric evaluation was available. The aim of this research was to assess efficacy and safety of switching to tenofovir (TDF) in the context of the multidisciplinary interventions offered in the Metabolic Clinic comprehensive of: dietary counseling, physical activities, surgical treatment for facial lipoatrophy or fat hypertrophy and psychological support. In a cohort of 189 people with lipodystrophy, TDF was part of the antiretroviral regimen in 125 individuals (82 males e 43 females). TDF-control group was made of 64 individuals (38 males e 26 females). The two study groups were homogeneous for metabolic, morphologic and psychometric profile at baseline. In the follow up period a significant improvement was observed in TDF+ group with regard of blood glucose, insuline, triglyceride. Non significant change in morphologic alterations evaluated with DEXA was observed in the two study groups. With regards of psychometric evaluations, a striking improvement was observed in aesthetic satisfaction of the face, of the body, of body image and depression. In the cohort, no progressions of HIV disease nor serious adverse events were observed. We conclude that switching to tenofovir in the context of the multidisciplinary interventions offered in the Metabolic Clinic is efficacious and safe in the management of LD