Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients

Abstract

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.

Elevated homocysteine levels in human immunodeficiency virus-infected patients under antiretroviral therapy: A meta-analysis

“…Nine of the 12 studies reported that the mean Hcy concentration was greater in HIV-infected individuals compared to controls. Only five [33,34,36,38,39] and four [33,36,38,39] of the included studies described quantitative folate and vitamin B12 data, respectively (Table 1). A meta-analysis performed on outcome 1 indicated that the plasma Hcy levels in HIV-infected patients were 2.05 µmol/L higher than the plasma Hcy levels in uninfected controls (95%CI: 0.13-4.01, P < 0.01; [30] Norway 15/21 CS 9.2 ± 7.3 9.0 ± 5.0 ---Naisbitt et al [31] England 33/33 CS 11.9 ± 4.7 14.5 ± 5.6 ---Bernasconi et al [32] Swaziland 80/73 COS 7.6 ± 3.6 8.…”

“…A meta-analysis performed on outcome 1 indicated that the plasma Hcy levels in HIV-infected patients were 2.05 µmol/L higher than the plasma Hcy levels in uninfected controls (95%CI: 0.13-4.01, P < 0.01; [30] Norway 15/21 CS 9.2 ± 7.3 9.0 ± 5.0 ---Naisbitt et al [31] England 33/33 CS 11.9 ± 4.7 14.5 ± 5.6 ---Bernasconi et al [32] Swaziland 80/73 COS 7.6 ± 3.6 8. 2 Remacha et al [23] Spain 128/235 CS 7.5 ± 7.8 14.3 ± 12.9 6.2% control; -B12 368.6 ± 219 Raiszadeh et al [35] United Castagna et al [29] Müller et al [30] Naisbitt et al [31] Vilaseca et al [33] Bernasconi et al [32] Remacha et al [23] de Larrañaga et al [34] Raiszadeh et al [35] Vigano et al [36] Borges-Santos et al [38] Abdollahi et al [37] Deminice et al [39] Total (95%CI) …”

“…Borge s-Santos et al [38] Deminice et al [39] Larrañaga et al [34] Vigano et al [36] Vilaseca et al [33] Total (95%CI) Borges-Santos et al [38] Deminice et al [39] Larrañaga et al [34] Vilaseca et al [33] Total ( patients who were exposed to ART compared to patients who were not exposed to ART. In addition, HIVinfected patients presented decreased plasma levels of folate, but not vitamin B12.…”

“…The present study demonstrates that HHcy can be included on this list. Different classes of antiretroviral drugs and time exposed to the treatment may generate different ART- Mercié et al [42] France 78/304 COS 12.5 ± 4.8 11.5 ± 4.3 --de Larrañaga et al [34] Argentina 31/128 CS 9.7 ± 7.1 8.0 ± 6.1 --Remacha et al [23] Spain 128/235 CS 17.3 ± 13 8.2 ± 7.8 -Patients under ART (taking > 3 antiretroviral drugs) Martí-Carvajal et al [41] Venezuela 14/40 CS 10 ± 7.5 9.2 ± 6.7 48.6% non-ART; 45.5% ART -Currier et al [42] United 40/41 COS 9.6 ± 5 8.0 ± 6.1 -Patients on ART including a PI continuously for 2 yr States Raiszadeh et al [35] United 127/249 COS 7.5 ± 2.8 7.3 ± 2.4 --States Coria-Ramirez et al [43] Mexico 69/69 CC 24.8 ± 14.6 7.9 ± 3.4 7.3% non-ART; 79.9% ART Patients who began ART and maintained the treatment for 6 mo Table 2 Characteristics of studies included in the outcome 2 CC: Case-control; CS: Cross-sectional; COS: Cohort study; Hcy: Homocysteine; HHcy: Hyperhomocysteinenemia; PI: Protease inhibitors; ART: Antiretroviral therapy.…”

Manifestações cardiovasculares em pacientes com infecção pelo vírus da imunodeficiência humana

“…Laboratory evidence shows an increase in von Willebrand and tissue plasminogen activator factors, two markers of endothelial dysfunction. It seems that their levels are directly related to the viral load, cytokines and advanced stage of the disease 100 . The pathophysiological mechanism has not been fully explained, but it seems to be mediated by the synergism between HIV-1 Tat protein (released by infected cells) and TNF-α 101 .…”