Influence of immune activation and inflammatory response on cardiovascular risk associated with the human immunodeficiency virus

Figures & data

Figure 1 Determining factors of CVD in HIV-infected individuals.

Notes: In addition to lifestyle and individual predisposition, HIV-infected patients present other factors that determine CVD. HIV itself determines a state of persistent inflammation and immune activation, metabolic abnormalities, and vascular dysfunction. On the other hand, although some antiretroviral drugs may be associated with some deleterious alterations, ART has a positive net impact on inflammation, immune activation, and endothelial dysfunction that overcomes the possible deleterious effects associated with some drugs (note that the green lines are thicker than the orange ones). Finally, patients with HIV infection are frequently coinfected with HCV, CMV, or herpes viruses that may contribute to CVD by promoting chronic inflammation and immune activation.
Abbreviations: HIV, human immunodeficiency virus; ART, antiretroviral therapy; CVD, cardiovascular disease; HCV, hepatitis C virus; CMV, cytomegalovirus.

Table 1 Biomarkers of inflammation, immune activation, and endothelial dysfunction associated with CVD in the general population and performance in HIV-infected patients

	Association with CVD in non-HIV patients	Effect of HIV*	Effect of ART**	Association with CVD in HIV-infected patients
Inflammation
hsCRP	↑↑ in CVD patients and predicts incident CVD^Citation164^–^Citation167	↑↑^Citation110	↓↓^Citation124,Citation130	CVD^Citation115,Citation116 (not seen in Ford et al^Citation168)
IL-6	↑↑ in CVD patients and predicts incident CVD^Citation169^–^Citation172	↑↑^Citation110	↓↓^Citation131	CVD^Citation116^–^Citation118
sTNFR	↑↑ in LVH^Citation173 Predicts HF in CAD^Citation174^–^Citation176	↑↑^Citation113,Citation124	↓↓^Citation124,Citation131	Subclinical atherosclerosis (IMT)^Citation113,Citation120 CVD^Citation119
Monocyte activation
sCD163	↑↑ in CAD, PAD, subclinical atherosclerosis^Citation177^–^Citation179	↑↑^Citation58,Citation59,Citation123,Citation124	↓↓^Citation123,Citation124	Subclinical atherosclerosis (CoP)^Citation125,Citation126 (not seen for IMT in Longenecker et al^Citation120) No prediction of first AMI^Citation180,a
sCD14	Associated with subclinical atherosclerosis and incident CVD^Citation181	↑↑^Citation58^–^Citation60	⇄^Citation137,Citation138	Subclinical atherosclerosis (CAC,^Citation128 IMT^Citation182) (not seen for IMT in Longenecker et al^Citation120)
CD14+/CD16+ expansion	Associated with incident CVD^Citation183^–^Citation185 (not seen in Jaipersad et al^Citation186 and Berg et al^Citation187)	↑↑^Citation58,Citation59	↓↓^Citation123,Citation136,b	Subclinical atherosclerosis (CAC)^Citation129 (no association with IMT in Barbour et al^Citation188)
Endothelial disturbances
sVCAM-1	↑↑ in CVD patients and predicts incident CVD^Citation189,Citation190	↑↑^Citation111^–^Citation113	↓↓^Citation130^–^Citation133	Subclinical atherosclerosis (IMT, CaP^Citation120,Citation121) (not seen in Hileman et al^Citation191)
sICAM-1	↑↑ in CVD patients and predicts incident CVD^Citation165,Citation189^–^Citation190	↑↑^Citation111^–^Citation113	↓↓^Citation130^–^Citation133	No association with IMT in Hileman et al^Citation191
ADMA	↑↑ in CVD patients and predicts incident CVD^Citation192,Citation193	↑↑^Citation114,Citation124	↓↓^Citation134,Citation135 (not seen in Beltrán et al^Citation124)	Subclinical atherosclerosis (CAC^Citation122) PAH^Citation194
sTWEAK	↓↓ in CVD patients^Citation179,Citation195,Citation196 Low levels predict CV outcomes in PAD, HF, and CKD patients^Citation197^–^Citation199	↓↓^Citation124	⇄^Citation124	Not known

Notes:

* Comparison of HIV-infected patients versus non-HIV-infected controls.

** Comparison of HIV-infected patients prior to and after initiating ART.

a Nested case-control study.

b HIV-infected patients receiving ART presented with a lower proportion of CD16+ monocytes; no comparison prior to versus after ART.

Abbreviations: CVD, cardiovascular disease; HIV, human immunodeficiency virus; hsCRP, high sensitivity C-reactive protein; IL, interleukin; sTNFR, soluble receptors of tumor necrosis factor; LVH, left ventricular hypertrophy; HF, heart failure; IMT, intima–media thickness; CAD, coronary artery disease; PAD, peripheral artery disease; CoP, coronary plaques; AMI, acute myocardial infarction; CAC, coronary artery calcium; sVCAM-1, soluble vascular cell adhesion molecule-1; CaP, carotid plaques; sICAM-1, soluble intercellular adhesion molecule-1; ADMA, asymmetric dimethylarginine; PAH, pulmonary arterial hypertension; sTWEAK, soluble tumor necrosis factor-like weak inducer of apoptosis; CV, cardiovascular; CKD, chronic kidney disease; ART, antiretroviral therapy.

Figure 2 Factors implicated in persistent inflammation and immune activation in HIV patients.

Notes: HIV-infected patients have a persistent state of inflammation and immune activation in spite of the suppression of HIV replication via ART. Various factors might be implicated: 1) homeostatic drive: after reaching an immune/inflammatory set point, the immunological and inflammatory response persist in spite of eliminating the initial stimulus; 2) residual nondetected HIV replication; 3) proinflammatory effects of certain antiretroviral drugs; 4) translocation of bacterial products through damaged intestinal mucosa; 5) coexistence of chronic HCV or herpes virus infection, common in the HIV population; and 6) established vascular lesions.
Abbreviations: HIV, human immunodeficiency syndrome; ART, antiretroviral therapy; HCV, hepatitis C virus.

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