Cardiovascular magnetic resonance assessment of subclinicalcardiovascular abnormalities before and after the initiation of antiretroviral therapy in HIV-infected South Africans - PROJECT SUMMARY Despite modern anti-retroviral treatment (ART), cardiovascular disease (CVD) remains a risk factor for mortality in people living with HIV (PLWH). CVD in PLWH is heterogenous and disease profiles differ between high-income countries and low-to middle-income countries. A considerable burden of subclinical CVD is thought to be present in persons before the initiation of ART and these abnormalities may be precursors of more advanced disease if the underlying pathological processes are not halted. The mechanisms underlying the development of CVD in treatment naïve PLWH remain largely unknown, as does the modifying effect of ART on these abnormalities. Cardiovascular magnetic resonance imaging (CMR) is a comprehensive, non-invasive cardiovascular examination tool that is superior to other imaging techniques in diagnosing early cardiovascular abnormalities. CMR can characterize tissues that allow interrogation of underlying pathological processes with quantitative myocardial mapping techniques, but its use has been limited in developing countries due to limited expertise. The development of CMR-expertise and personnel with the capacity to train and certify CMR-operators in underserviced low- to middle-income countries is required to advance clinical care and research. A multi-modal research approach offers distinct advantages by utilizing the strengths of various techniques to conduct high-quality, mechanistic research. We aim to perform a series of prospective, multimodal cardiovascular research studies with a focus on exploring the underlying mechanisms of CVD to improve our understanding of HIV-infection’s effect on the heart and characterize the transition of people living with HIV from a state of ART naivety to ART. We will utilize an established South African research cohort of 85 newly diagnosed PLWH, and an age- and sex matched HIV-uninfected control group (n=22). In addition, we will include a completed prospective research arm containing 73 persons from the HIV-infected group that completed 9-months of ART. We will investigate the inflammatory pathways associated with the previously described heart muscle oedema and fibrosis in the cohort by measuring and describing an extensive serum cytokine-panel evaluating the inflammatory cascade at multiple levels, and correlating select cytokines with previously published CMR- multiparametric myocardial mapping data (a “virtual, quantitative biopsy” of myocardium). Furthermore, we will prospectively measure carotid-femoral pulse wave velocity (a validated marker of cardiovascular risk) and characterize the cohort’s atrial morphology and function (using CMR and echocardiographic speckle tracking) before and after the initiation of ART in newly diagnosed PLWH as an early marker of CVD. We will also build local CMR-expertise and research capacity to lay the foundation for a planned NIH R01 application. Our proposed study will contribute mechanistic data on the early impact of HIV on the heart, as well as the influence of ART on these abnormalities. We aim to address key knowledge gaps that will aid the development of future screening, monitoring, and treatment strategies to improve the health of PLWH locally and globally.
