Ricerc@Sapienza

Life expectancy has substantially increased in humans with the immunodeficiency virus (HIV) infection. Insulin resistance, diabetes, dyslipidemia, lipodystrophy, hypothyroidism, hypogonadism, muscle weakness, and osteoporosis are commonly seen as the combined effect of viral factors, host immune response or HIV-treatment drugs. In the long term, HIV infection results in a condition of persistent low-grade inflammation associated with changes in cell trafficking through the endothelial barrier, formation of proatherogenic monocytes, altered response and metabolism of steroid hormones, all contributing to metabolic and cardiovascular failure. Aim of the study is to describe at the molecular level such changes and test whether the inhibition of phosphodiesterase type-5 (PDE5i) can improve endothelial function in HIV controlling the chronic inflammation and improving metabolism. A group of 16 investigators from 3 Departments - 2 full professors, 5 associate and 3 junior professors and 6 young researchers (PhD or post-doc) - have designed a clinical trial addressing this hypothesis based on solid data accumulated in conditions mirroring some of the long-term alterations observed in HIV: metabolic syndrome, adipose tissue dysfunction, hypogonadism, and glucocorticoid excess. The group has published several clinical trials, and experimental studies, in HIV, steroid hormones, and the pharmacological modulation of the PDE5 on such outcomes, with a track record generating nearly >460 points of IF from non-duplicated publications. The project is reverse translational -from bed to benchside- with the potential to disclose novel diagnostic and therapeutic tools targeting end-organ complications in chronic inflammation. The homogenous composition of the group with participants at every level, from senior to young researchers, the experience in the field and the availability of co-funding offer a greater warrant of success of output delivery.