Interaction of Antiretroviral Drugs with the Microbiome & Implications on the development of cardiovascular diseases in HIV+ persons: A Study Protocol

Abstract Background The longevity of people living with HIV has been enhanced by the introduction of antiretroviral (ARV) drugs in the mid-90s. Antiretroviral therapy (ART) is now mandatory for all persons who test HIV positive in South Africa and the government policy is to start treatment upon diagnosis. The ART is based on protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) and both groups of drugs have been reported to have deleterious side effects manifesting as HIV-associated lipodystrophy syndrome, metabolic syndrome and cardiovascular diseases. HIV infection also causes dislocation of the gut microbiota which also contribute towards the observed systemic inflammation even before patients are on ART. The aim of this study is find the relationship between HIV infection, ART, endothelial function, and gut microbial dynamics and how they influence development of cardiovascular disease (CVD) and metabolic syndrome. Presented here is the detailed study protocol. Methods This is a longitudinal study to be conducted over a period of two years. Newly diagnosed patients of both genders enrolled for the ART programme will be recruited and blood, stool and anthropometric measurements will be collected every 6 months. Endothelial function, measured by non-invasive methods i.e. flow-mediated dilation and retinal microvasculature assessment. Lipid profile, viral load and other relevant blood parameters will be measured using routine methods employed by the National Health Laboratory Services in Mthatha, South Africa. Stool samples will be used for metagenomic analysis to characterise changes in the gut microbial richness and abundance. The 16S rRNA gene will be PCR amplified and amplicons will be sequenced using a next-generation sequencing platform. Multivariate analysis will be used to determine the nature of the relationship between blood chemistry parameters, gut microbial profile, endothelial function and anthropometric data. Impact of project : The study aims to determine changes in vascular function and gut flora in the in persons living with HIV on the ART programme, subsequently providing a platform for development of corrective and therapeutic nutraceuticals and probiotics for the same population.