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Title: Cardiac abnormalities in HIV infected older children and adolescents in Zimbabwe
Author: Majonga, E. D.
ISNI:       0000 0004 7659 5282
Awarding Body: London School of Hygiene & Tropical Medicine
Current Institution: London School of Hygiene and Tropical Medicine (University of London)
Date of Award: 2018
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The global scale-up of antiretroviral therapy (ART) has resulted in a dramatic decline in mortality in HIV infected individuals. Longstanding HIV infection is associated with an increased risk of chronic co-morbidities. One of the most wellrecognised co-morbidities is cardiac disease. An increased risk of cardiac disease in HIV infected children was reported in the pre-ART era, but the burden and natural history in the ART-era, particularly in SSA is not known. Assessment of cardiac abnormalities is further complicated by the lack of regional (African) echocardiographic references ranges for healthy children. The main aims of this research were to establish echocardiographic reference ranges for older children in sub-Saharan Africa (SSA), and to determine the prevalence, incidence and progression of, and risk factors for cardiac abnormalities in children with HIV established on ART. A total of 282 healthy HIV-uninfected children aged 6-16 years with no known history of cardiac disease were enrolled to derive echocardiographic reference ranges. Standard M-mode and two-dimensional echocardiography was performed following the American Society of Echocardiography guidelines and a gamma-weighted model was used to calculate the z-scores for ventricular and atrial dimensions. The first echocardiographic references (z-scores) were established for older children in SSA and were normalised to body surface area. A total of 201 children with HIV aged between 6 and 16 years, taking ART for at least 6 months and clinically stable underwent transthoracic echocardiography, using a standard protocol at baseline and at 18 months. A total of 197 had echocardiograms at baseline and abnormalities were found in 83 (42%); left ventricular (LV) diastolic dysfunction was commonest in 45 (23%) and LV hypertrophy (LVH) in 22 (11%). Right ventricular (RV) dilatation and systolic dysfunction were found in 13 (7%) and 4 (2%) respectively, of whom 60% had concurrent left heart abnormalities. Current use of nevirapine and hypertension were associated with LVH and LV diastolic dysfunction respectively. A total of 175 (89%) participants were followed up for 283.9 person-years (pys). Ten participants developed left heart and 16 developed right heart abnormalities constituting an incidence of left and right heart abnormalities was 3.52 and 5.64 per 100 pys respectively. The risk of RV dilatation was highest, 12/163 (7%) Stunting was associated with development of any new cardiac abnormality (aOR 2.59 (95% CI, 1.03-6.49; p=0.043). Cardiac abnormalities persisted at follow up in majority of participants. Cardiac abnormalities present at baseline reverted to normal at 18 months in 11(6%). There was an overall increase in mean z-scores for LV, left atrial, LVH, interventricular septal and LV posterior wall diameters at 18 months (p < 0.001). Despite ART, children with HIV have a high prevalence and incidence of cardiac abnormalities, with only a minority being transient. The increase in mean zscores for LV, left atrial, LVH, interventricular septal and LV posterior wall diameters a short period of follow up suggests potential for progression of cardiac abnormalities. Longer follow up is recommended to understand the clinical implications of these abnormalities.
Supervisor: Ferrand, R. A. ; Kaski, J. P. Sponsor: Norwegian Research Council (GLOBVAC)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral