Direct and indirect cardiovascular and cardiometabolic sequelae of the combined anti-retroviral therapy on people living with HIV

Abstract

With reports of its emergence as far back as the early 1900s, human immunodeficiency virus (HIV) has become one of the deadliest and most difficult viruses to treat in the era of modern medicine. Although not always effective, HIV treatment has evolved and improved substantially over the past few decades. Despite the major advancements in the efficacy of HIV therapy, there are mounting concerns about the physiological, cardiovascular, and neurological sequelae of current treatments. The objective of this review is to (Blattner et al., Cancer Res., 1985, 45(9 Suppl), 4598s–601s) highlight the different forms of antiretroviral therapy, how they work, and any effects that they may have on the cardiovascular health of patients living with HIV, and to (Mann et al., J Infect Dis, 1992, 165(2), 245–50) explore the new, more common therapeutic combinations currently available and their effects on cardiovascular and neurological health. We executed a computer-based literature search using databases such as PubMed to look for relevant, original articles that were published after 1998 to current year. Articles that had relevance, in any capacity, to the field of HIV therapy and its intersection with cardiovascular and neurological health were included. Amongst currently used classes of HIV therapies, protease inhibitors (PIs) and combined anti-retroviral therapy (cART) were found to have an overall negative effect on the cardiovascular system related to increased cardiac apoptosis, reduced repair mechanisms, block hyperplasia/hypertrophy, decreased ATP production in the heart tissue, increased total cholesterol, low-density lipoproteins, triglycerides, and gross endothelial dysfunction. The review of Integrase Strand Transfer Inhibitors (INSTI), Nucleoside Reverse Transcriptase Inhibitors (NRTI), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) revealed mixed results, in which both positive and negative effects on cardiovascular health were observed. In parallel, studies suggest that autonomic dysfunction caused by these drugs is a frequent and significant occurrence that needs to be closely monitored in all HIV + patients. While still a relatively nascent field, more research on the cardiovascular and neurological implications of HIV therapy is crucial to accurately evaluate patient risk.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men living with HIV

“…Further, the availability of objective HIV-specific factors (i.e., viral load and CD4 + cell count) would have provided clarity as to the impact of HIV-specific factors on ASCVD risk, and if these vary by sex [18,21]. Additionally, although it is now well documented than INSTIs are associated with better cardiovascular risk profiles compared to other classes of ART, INSTIs were not the preferred line of drug during the entire time 2011–2019 time period, which limits our ability to detect sex-based differences in ASCVD risk associated with drug class [30–32]. Although we were able to examine the relationships between age and ASCVD risk among WLHIV, we did not have data on menopausal status, which would have provided further insight into the mechanisms influencing sex-specific ASCVD risk among PWH [18,33,34].…”

Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens

“…In the PI group, however, only 13 (22%) of 59 patients were treated with ATV (8 ATV/r and 5 unboosted ATV); moreover, we was not able to identify the impact of the different PIs on the development of cardiovascular diseases. However, the intent of the study is to evaluate the cardiovascular risk related altogether to the class of PIs, which was also highlighted in a recent review of Batta et al [ 31 ].…”

HIV infection and ART use are associated with altered plasma clot characteristics in Black South Africans

“…Altered clot structure is a known contributing factor in thrombotic-related cardiovascular complications [ 19 ], as clots with tightly packed, dense fibrin networks tend to be more resistant to lysis and contributing to thromboembolic events [ 19 , 20 ]. This may result in adverse complications such as stroke and myocardial infarction, which are also evident in PLWH [ 12 , 14 , 17 ].…”

“…The global community persists in employing strategies to improve ART, expand its coverage and enhance compliance among users with a view to improving health and reducing new infection rates [8,9]. However, evidence has emerged that demonstrates cardiovascular disease (CVD) to be a growing concern and a leading cause of morbidity and mortality among PLWH on ART [10][11][12]. It is reported that ART use is associated with increased inflammation, dyslipidaemias, endothelial lining injuries as well as altered coagulation [13][14][15].…”