Long term effects in chronic HIV infection; clinical and laboratory studies
Lange termijn complicaties in chronische HIV infectie; klinische en laboratorium studies
Without treatment, end-stage HIV infection is accompanied by a high prevalence of opportunistic infections. This prevalence has dropped dramatically after the introduction of cART. During effective treatment the burden of neurologic complications is also small, but not negligible. There is considerable debate about the prevalence, pathogenesis and clinical relevance of certain neurological complications such as stroke, neurocognitive disease and the residual risk of opportunistic infections. To understand the interplay between HIV and the CNS, we first reviewed current literature. In addition, a cross-sectional cohort study at the Erasmus MC is described. The goal was to assess the prevalence of cognitive disorders in a chronically infected and well-treated HIV population. An appropriate screening strategy as advised by the European AIDS Clinical Society was applied and assessed for sensitivity and specificity using the Neuropsychological Assessment as a gold standard. Also, socio-economic characteristics of the patients involved in the TREVI study are described. It focuses on various factors involved in the quality of life and labor participation. We collected blood specimens during the TREVI study and isolated plasma and peripheral blood mononuclear cells (PBMC’s) to investigate immune activation in a well-treated HIV-infected population at different treatment intervals. This experiment was designed to assess the effect of long-term treatment on the expression of pro-inflammatory cytokines in PBMC’s and plasma. Further more, we applied a novel tool to assess the risk for metabolic complications by measuring hair cortisol. Based on anthropomorphic and laboratory data, we identified patients with the metabolic syndrome and investigated whether this was correlated to cortisol levels. In contrast to uninfected individuals, people living with HIV at increased risk for the metabolic syndrome had low hair cortisol levels. This finding inspired us to initiate a follow up study. For this part, we tested the sensitivity of PBMCs of HIV infected individuals to corticosteroids. Specific elements of the coagulation cascade were also investigated. Von Willebrand Factor (vWF), an important protein in the induction of hemostasis, was measured in patients with and without a history of thrombosis. Using vWF as a predictive marker, we assessed whether symptomatic disease is linked to the level of this biomarker. In the last part of this manuscript, we evaluated the levels of circulating endothelial cells (CECs) in HIV-infected children. CECs represent the turnover rate and degradation of the endothelial lining of the vessel walls. Current literature already demonstrates an increase of CECs under pathological conditions, particularly cancer and sickle cell anemia. Using CECs as a correlate of vascular damage, we investigated the impact of chronic HIV infection on the endothelium.
|Keywords||HIV, Neurologic disorders, coagulation, immune activation, circulating endothelial cells, cortisol, metabolic syndrome, von willebrand factor|
|Promotor||E.C.M. van Gorp (Eric) , K.S. Adriani (Kirsten) , A.M.C. van Rossum (Annemarie)|
|Publisher||Erasmus University Rotterdam|
van den Dries, L.W.J. (2018). Long term effects in chronic HIV infection; clinical and laboratory studies. Retrieved from http://hdl.handle.net/1765/109163
|Stellingen-LvdD.pdf , 91kb|