Table 1.

A synopsis of studies reporting on endothelial dysfunction and cardiovascular disease (CVD)-risk in people living with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART).

Author, year	Country	Study design	Study population	Type of HAART regimen	Key findings
[32]	United States	Cross-sectional study	PLWH (n = 37) on HAART, with an average age of 42 years (81 % male), without chronic lifestyle diseases. No reported ethnicity	1 participant took amprenavir (APV), 11 indinavir (IDV), 6 nelfinavir (NFV), 2 RTV, 6 saquinavir (SQV), 2 abacavir (ABC), 3 didanosine (ddI), 18 lamivudine (3 TC), 8 stavudine (d4T), 6 zidovudine (ZDV), 2 delaviridine (DLV), and 3 nevirapine (NVP). Participants were monitored for ≥6 months	Participants presented with increased total cholesterol and triglyceride levels, characterized by high concentrations of very low-density lipoprotein (vLDL). This was followed by endothelial dysfunction marked by impaired flow mediated dilation (FMD)
[33]	United States	Randomized controlled trial	PLWH (n = 82) on HAART, with an average age of 35 years (91 % male). Mixed ethnic groups, White (54 %), Black/Asian (32 %), and Hispanic (15 %)	NRTIs plus EFV, NRTIs plus lopinavir/ritonavir (LPV/r), or a NRTI-sparing regimen of EFV plus LPV/r. Participants were monitored for up to 6 months	Participants presented with improved endothelial function demonstrated increased FMD
[34]	Switzerland	Randomized controlled trial	PLWH (n = 145) on HAART, with an average age of 34 years (62 % females). Thai (100 %) ethnicity	RTV boosted SQV/d4T, TDF/3 TC, TDF/FTC. Participants were monitored for up to 6 months	Participants presented with marked decrease in markers of endothelial dysfunction, soluble- vascular cell adhesion molecule 1 (VCAM-1), P-selectin, leptin, and D-dimer, whereas mediators of anti-inflammation like adiponectin and interleukin (IL)-10 were increased after initiation of HAART. However, this effect was diminished at 12 weeks after randomization, and even associated with increase in plasma HIV-RNA
[31]	Switzerland	Randomized controlled trial	PLWH (n = 39) on HAART, with an age between 18 and 65 years (77 % male). No reported ethnicity	20 participants taking ATV and 19 were on ATV-free PIs. Participants were monitored for up to 3 months	Participants on ATV presented with more pronounced effect in improved lipid profiles, including total cholesterol, high-density lipoprotein (HDL), and triglycerides. This included oxidised LDL, accompanied by endothelial dysfunction as shown by reduced FMD
[35]	Denmark	Longitudinal study	PLWH (n = 12) on HAART, with an age between 18 and 60 years (100 % male). White (100 %) ethnicity	9 participants were on TDF/FTC/EFV, 1 took 3TC/ZDV/EFV, 1 took 3TC/ABC/EFV, and 1 took TDF/FTC/raltegravir (RAL). Participants were monitored before and 5 weeks (24–67 days) after initiation of ART	Participants presented with reduced maximal myocardial perfusion and decreased myocardial perfusion reserve soon after initiating HAART. This was accompanied by endothelial dysfunction as seen with reduced FMD
[36]	United States	Randomized controlled trial	PLWH (n = 50) on HAART, with an average age of 43 years (84 % males). White (66 %) ethnicity	26 participants switched to ATV (all continued RTV); 24 remained on their PIs. Participants were monitored for up to 6 months	Participants switched to zidovudine presented with improved total cholesterol, triglycerides, and HDL levels. However, endothelial function as measure by FMD was not affected, including inflammatory and metabolic markers
[37]	United States	Randomized controlled trial	PLWH (n = 101) on HAART, with an average age of 34 years (68 % male). Mixed ethnicity, African American (60 %), Hispanic (38 %), and Asian (2 %)	51 participants took fosamprenavir (FPV)/RTV; 50 took EFV/ABC/3 TC. Participants were monitored after 24 months	Participants presented with improved cardiovascular biomarkers. This included favourable decline in thrombotic activity (marked by D-dimer) and endothelial activation (marked by VCAM-1). However, inflammation increased as reflected by high sensitivity C-reactive protein (hs-CRP)
[38]	France	Randomized controlled trial	PLWH (n = 44) on HAART, with an average age of 41 years (93 % male). No reported ethnicity	ZDV/RTV (300/100 mg), plus a fixed combination of either ABC/3 TC (600/300 mg) or FTC/TDF (200/245 mg) for 24 months	Participants presented with stable markers of inflammation (hs-CRP, IL-6) and endothelial activation (VCAM-1) during the treatment period
[39]	Botswana	Randomized controlled trial	PLWH (n = 112) on HAART, with an average age of 40 years (51 % females). Black African (100 %) ethnicity	In addition to a nonnucleoside reverse transcriptase inhibitor (NNRTIs) (73 %) or PI (26 %), the HAART regimen backbone consisted of either TDF/3 TC (49 %), ZDV/3 TC (47 %), ABC/3 TC (2 %) or 3 TC (2 %) for 14 months	Participants presented with endothelial dysfunction, marked by elevated intercellular adhesion molecule 1 (ICAM-1) and VCAM-1. Monocyte activation marker (sCD163) was also associated with increased ICAM-1. However, inflammatory marker, IL-6 was not affected
[40]	South Africa	Case-control	PLWH (n = 100) on HAART, with an average age of 43 years (75 % female). Black African (100 %) ethnicity	TDF/FTC/EFV or TDF/3TC/EFV Participants were monitored over 18 months	Participants presented with comparable markers of endothelial dysfunction and cardiometabolic profiles to HIV-free individuals. The %FMD was reduced in some participants, based on socio-economic differences