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This health challenge stimulated significant research interests in the field, leading to an improved understanding of both lifestyle-related risk factors and the underlying mechanisms of CVD onset in PLHIV. However, despite such progress, the precise role of various risk factors and mechanisms underlying the development of HIV-mediated CVD still remains relatively poorly understood. Therefore, we review CVD onset in PLHIV and focus on 1) the spectrum of cardiovascular complications that typically manifest in such persons and 2) underlying mechanisms that are implicated in this process. Here, the contributions of such factors and modulators and underlying mechanisms are considered in a holistic and integrative manner to generate a unifying hypothesis that includes identification of the core pathways mediating CVD onset. The review focuses on the sub-Saharan African context, as there are relatively high numbers of PLHIV residing within this region, indicating that the greater CVD risk will increasingly threaten the well-being and health of its citizens. It is our opinion that such an approach helps point the way for future research efforts to improve treatment strategies and\/or lifestyle-related modifications for PLHIV. <\/jats:p>","DOI":"10.1152\/ajpheart.00549.2019","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T17:43:08Z","timestamp":1582306988000},"page":"H731-H746","source":"Crossref","is-referenced-by-count":45,"title":["HIV-related cardiovascular diseases: the search for a unifying hypothesis"],"prefix":"10.1152","volume":"318","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-6097","authenticated-orcid":false,"given":"Leanne","family":"Dominick","sequence":"first","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Midgley","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa-Mari","family":"Swart","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Sprake","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3198-2927","authenticated-orcid":false,"given":"Gaurang","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Laher","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"},{"name":"Department of Anesthesiology, Pharmacology, and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danzil","family":"Joseph","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2628-7196","authenticated-orcid":false,"given":"Eman","family":"Teer","sequence":"additional","affiliation":[{"name":"Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-4294","authenticated-orcid":false,"given":"M. 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