Immunopathology of hypertension in HIV-infected adults

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Masenga, Sepiso K.
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The University of Zambia.
Hypertension is a risk factor for stroke, end-organ damage and death. HIV positive individuals are more likely to have hypertension compared to the HIV-negative population, however, the underlying mechanisms are still unknown. Recently, researchers have discovered that chronic immune-activation/inflammation induces and propagates hypertension in humans. Excess dietary salt and infections among others, have been implicated as contributors to hypertension in the HIV-negative population but have not been well studied in HIV-positive individuals. This study was therefore conducted to determine the risk factors, and inflammation markers associated with hypertension as well as to confirm the effect of salt intake on blood pressure and immune cell activation in HIV positive patients. This study was a mixed research designs namely cross-sectional, interventional and systematic studies. Six cohorts were recruited at Livingstone Central Hospital (Zambia) and Vanderbilt University (USA) to achieve the objectives. Flow cytometry was employed to analyse cell markers and quantify cytokines. Cells were stimulated using lipopolysaccharide and Phorbol-12-Myristate-13-Acetate (PMA) in Roswell Park Memorial Institute (RPMI) media. Ion-selective electrode technology was used to quantify electrolytes in plasma and urine. For data collection, the international physical activity questionnaire (IPAQ), 24-hour recall form and the World Health Organisation STEPwise approach to surveillance form was adapted and used. Wilcoxon rank-sum test, Kruskal Wallis test, Chisquare and Dunn’s multiple comparisons test were used for data analyses. Finally, regression models to predict the impact of selected variables on hypertension, salt sensitivity and all the response variables was used. Results In multivariate logistic regression, age, body mass index, employment status, table salt consumption, fasting blood sugar, waist circumference, minutes of moderate physical activity, and sedentary hours, were risk factors significantly associated with hypertension in a Zambian cohort of 226 HIV positive participants, p<0.05. Neutrophil count, neutrophil-to-lymphocyte ratio, erythrocytes and creatinine, and a low glomerular filtration were also associated with hypertension. In a cohort of 43 HIV positive participants and 42 HIV negative control group, hypertensives in the HIV positive group had higher IL-6, IL-10, CD80+ expression on total leucocytes and isolevuglandin expression inside monocytes adjusted for sex, age, body mass index and duration on antiretroviral therapy. In a cohort of 70 HIV positive participants from the United States of America (USA), eosinophil count was associated with hypertension and this report was consistent in two HIV-negative control cohorts comprising of 50 and 81, 039 participants respectively. In a systematic study comprising 45 African countries, Norway and the USA, studies revealed that IL-17A, interferon-gamma, and CD4 cells were associated with hypertension in HIV-infected adults. In a Zambian cohort of 85 participants, salt sensitivity was associated with higher levels of IL-6, monocytes, isolevuglandin-adducts inside monocytes, 24-hour sodium and chloride excretion. Hypertensive HIV positive individuals exhibit high inflammatory (IL-6, IL-10, Isolevuglandin-laden monocytes) and immune-activation markers (CD45 CD80+) compared to normotensives. Eosinophilia is a likely feature of inflammation associated with hypertension in virally suppressed HIV positive individuals. Salt-sensitive hypertension was highly prevalent. Hence, high dietary salt is likely to be a risk factor for the development of, or may worsen already existing hypertension. Salt sensitivity testing in clinical practice is therefore, recommended.
Thesis of Doctor of Philosophy in Immuno-Pathology.