Evaluating the reactivation of herpesviruses and inflammation as cardiovascular and cerebrovascular risk factors in antiretroviral therapy initiators in an African HIV-infected population (RHICCA): a protocol for a longitudinal cohort study



Peterson, Ingrid, Ntsui, Ntobeko, Jambo, Kondwani ORCID: 0000-0002-3195-2210, Kelly, Christine, Huwa, Jacqueline, Afran, Louise ORCID: 0000-0003-4417-6318, Tatuene, Joseph Kamtchum ORCID: 0000-0002-1041-4202, Pett, Sarah, Henrion, Marc Yves Romain, Van Oosterhout, Joep
et al (show 15 more authors) (2019) Evaluating the reactivation of herpesviruses and inflammation as cardiovascular and cerebrovascular risk factors in antiretroviral therapy initiators in an African HIV-infected population (RHICCA): a protocol for a longitudinal cohort study. BMJ OPEN, 9 (9). e025576-.

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Abstract

<h4>Introduction</h4>In Sub-Saharan Africa, the rising rates of cerebrovascular and cardiovascular diseases (CBD/CVD) are intersecting with an ageing HIV-infected population. The widespread use of antiretroviral therapy (ART) may confer an additive risk and may not completely suppress the risk associated with HIV infection. High-quality prospective studies are needed to determine if HIV-infected patients in Africa are at increased risk of CBD/CVD and to identify factors associated with this risk. This study will test the hypothesis that immune activation and dysfunction, driven by HIV and reactivation of latent herpesvirus infections, lead to increased CBD/CVD risk in Malawian adults aged ≥35 years.<h4>Methods and analysis</h4>We will conduct a single-centre, 36-month, prospective cohort study in 800 HIV-infected patients initiating ART and 190 HIV-uninfected controls in Blantyre, Malawi. Patients and controls will be recruited from government ART clinics and the community, respectively, and will be frequency-matched by 5-year age band and sex. At baseline and follow-up visits, we will measure carotid intima-media thickness and pulse wave velocity as surrogate markers of vasculopathy, and will be used to estimate CBD/CVD risk. Our primary exposures of interest are cytomegalovirus and varicella zoster reactivation, changes in HIV plasma viral load, and markers of systemic inflammation and endothelial function. Multivariable regression models will be developed to assess the study's primary hypothesis. The occurrence of clinical CBD/CVD will be assessed as secondary study endpoints.<h4>Ethics and dissemination</h4>The University of Malawi College of Medicine and Liverpool School of Tropical Medicine research ethics committees approved this work. Our goal is to understand the pathogenesis of CBD/CVD among HIV cohorts on ART, in Sub-Saharan Africa, and provide data to inform future interventional clinical trials. This study runs between May 2017 and August 2020. Results of the main trial will be submitted for publication in a peer-reviewed journal.<h4>Trial registration number</h4>ISRCTN42862937.

Item Type: Article
Uncontrolled Keywords: Cardiovascular, cerebrovascular, HIV, herpesvirus, Immune dysregulation
Depositing User: Symplectic Admin
Date Deposited: 03 Oct 2019 14:06
Last Modified: 19 Jan 2023 00:24
DOI: 10.1136/bmjopen-2018-025576
Open Access URL: https://bmjopen.bmj.com/content/9/9/e025576
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3056889