Curaçao Cohort Study - Adipokine-study
Student Project Protocol
Project code:
Duration: 4-6months
Student:
Daily coach Netherlands:
Daily coach Curaçao: Gonneke Hermanides, gonnekehermanides@gmail.com
Supervisor Curaçao: Prof Dr Duits
Senior tutor:
Background
Human immunodeficiency virus (HIV) lipodystrophy syndrome is a recognized syndrome characterized by body composition changes (fat redistribution) including the development of an enlarged posterior cervical fat pad, increased truncal adipositas, breast enlargement, peripheral fat loss and facial atrophy (1-4). Fat redistribution is associated with dyslipidemia and insulin resistance. Studies suggest that up to 83% of patients treated with protease inhibitor therapy develop fat redistribution (5), but fat redistribution has also been reported among non-PI-treated patients (2, 6). Hence it is possible that HIV itself, duration of exposure to the virus, or immune reconstitution might contribute to the development of the abnormal fat redistribution or metabolic abnormalities in HIV affected individuals.
Several molecules, such as TNF-α, leptin, resistin and adiponectin, are secreted by adipose tissue and exert significant metabolic effects on other tissues (7). These so-called adipokines might link the changes in adipose distribution and metabolic abnormalities in patients with HIV infection. Furthermore recent studies have shown adipose tissue to be an important immulogical organ (8). Few studies have been published whether alterations in adipokines might be related to immunologic changes during the disease course of HIVinfection including HIV lipodystrophy syndrome.
Institutions
Slotervaart Hospital, HIV Monitoring Foundation, Academic Medical Center, Amsterdam, the Netherlands. St. Elisabeth Hospital and Red Cross Foundation Bloodbank, Willemstad, Curaçao.
Study Location
St. Elisabeth Hospital and Red Cross Foundation Bloodbank, Willemstad, Curaçao.
Study objectives
Primary Objective: To assess the role of adipocytes in HIVinfection course and its complications like lipodystrophy syndrome.
Secondary Objectives: To assess the role of adipocytes by analysing serum levels of adipokines in different stages of HIV infection (correctorized by viral load, CD4 counts and clinical assessment) as predicting markers for HIVdisease course including lipodystrophy syndrome.
Tertiairy Objectives: To identify genetic host factors predisposing to incidence of HIV lipodystrophy syndrome.
Study methods
Observative cohort study of all individuals infected with HIV living in Curaçao treated at the outpatient clinic of drs C. Winkel, internist. Medical background and follow up are routinely collected at each consultation. Blood will be drawn routinely a week before the consultation. Blood will be centrifuged, aliquoted and routine measurements will be measured instantly and the remaining plasma will be stored for later measurements of e.g. adipokine measurement. Cytokines levels will be assessed by Enzyme Linked Immunosorbent Assay, viral load by real –time-PCR and CD4 by flowcytometry.
Study population
HIV infected adult patients between 16-80 years old. People who are using anabolic steroids, glucocorticoids or immune modulators will be excluded.
Student Project Goals
Primary student project goals: The student will characterise adipokine serum levels in a well defined cohort of a HIV infected population. This will include both untreated and treated patients over a defined time period. These results will be compared to levels in healthy controls. Furthermore serum levels of adipokines will be correlated with important parameters of HIV disease monitoring like CD4 count and viral load. Next to laboratory parameters adipokine levels will be assessed in relation to observed clinical complications like lipodystrophy.
Secondary student project goals: To assist the principal investigator in the inclusion procedure and to assist in the preparation of the needed study materials.
Student Project Time Schedule
Four monthly project during which the student will take care of the inclusion of patients, under supervision of the daily coach, G. Hermanides and supervisor prof. dr. A.J. Duits. During the last 2 weeks, the student will be given time to finish the study report and to present the results, in English, to the investigator group.
Literature
1. Dong KL, Bausserman LL, Flynn MM, Dickinson BP, Flanigan TP, Mileno MD, et al. Changes in body habitus and serum lipid abnormalities in HIV-positive women on highly active antiretroviral therapy (HAART). J Acquir Immune Defic Syndr 1999;21(2):107-13.
2. Miller KD, Jones E, Yanovski JA, Shankar R, Feuerstein I, Falloon J. Visceral abdominal-fat accumulation associated with use of indinavir. Lancet 1998;351(9106):871-5.
3. Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M. "Buffalo hump" in men with HIV-1 infection. Lancet 1998;351(9106):867-70.
4. Roth VR, Kravcik S, Angel JB. Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin Infect Dis 1998;27(1):65-7.
5. Carr A SK, Thorisdottir A, Kaufman GR, Chisolm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor associated lipodystrophy, hyperlipidemia, and diabetes mellitus: a cohort study. Lancet 1999;353:2093-9.
6. Hadigan C, Corcoran C, Stanley T, Piecuch S, Klibanski A, Grinspoon S. Fasting hyperinsulinemia in human immunodeficiency virus-infected men: relationship to body composition, gonadal function, and protease inhibitor use. J Clin Endocrinol Metab 2000;85(1):35-41.
7. Tong Q, Sankale JL, Hadigan CM, Tan G, Rosenberg ES, Kanki PJ, et al. Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices. J Clin Endocrinol Metab 2003;88(4):1559-64.
8. Schaffler A, Scholmerich J, Salzberger B. Adipose tissue as an immunological organ: Toll-like receptors, C1q/TNFs and CTRPs. Trends Immunol 2007;28(9):393-9.
