Immune Activation, Proinflammatory Cytokines, and Conventional Risks for Cardiovascular Disease in HIV Patients: A
Clara Brites-Alves1, Estela Luz1, Eduardo M Netto1
1LAPI - Laboratório de Pesquisa em Infectologia, Complexo Hospitalar Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
Insights
Interleukin-6 (IL-6) levels are linked to increased cardiovascular risk in HIV patients. Activated CD4+ T cells correlate with higher pro-inflammatory cytokine levels, highlighting immune markers in HIV-associated cardiovascular events.
Area of Science:
- Immunology
- Cardiology
- Infectious Diseases
Background:
- Cardiovascular events (CVE) are a significant cause of mortality in HIV patients.
- Antiretroviral therapy (ART), persistent immune activation, and lifestyle factors contribute to CVE risk.
- A case-control study was conducted to investigate coinfections and immune markers associated with CVE in HIV patients.
Purpose of the Study:
- To evaluate the role of coinfections and immune markers in cardiovascular events (CVE) among HIV patients on ART.
- To identify specific immune activation markers and cytokines associated with increased CVE risk.
Main Methods:
- A case-control study included HIV patients on ART with undetectable viral load for ≥12 months.
- Cases had CVE risk conditions; controls did not.
- Assessed viral infections, ART exposure, lifestyle factors, CD4/CD8 counts/ratios, immune activation markers (CD4CD38HLADR, CD8CD38HLADR), and eight cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, MIP-1α, IP-10).
Main Results:
- Cases were older and had higher creatinine and IL-6 levels than controls.
- No difference in CD4CD38HLADR+ or CD8CD38HLADR+ cell frequency between groups.
- Increased CD4CD38HLADR+ cells correlated with higher IP-10 and TNF-α levels overall.
- In controls, IL-6, TNF-α, and IP-10 correlated with CD4CD38HLADR+ cells.
- In hypertensive patients, CD4CD38HLADR+ cells correlated with IP-10.
- In hypercholesterolemic patients, CD4CD38HLADR+ cells negatively correlated with IL-2 and IL-6.
Conclusions:
- Elevated Interleukin-6 (IL-6) levels are associated with increased cardiovascular risk in HIV patients.
- Activated CD4+ T cells are linked to higher levels of pro-inflammatory cytokines, suggesting a role in HIV-associated CVE.
Background:
Cardiovascular events (CVE) are an increasing cause of morbi-mortality for HIV patients. The antiretroviral therapy (ART), persistent immune activation, and life style are factors that can increase CVE for such patients. We performed a case-control study to evaluate the role of coinfections and immune markers associated with CVE.
Methods:
We included patients under ART, with undetectable plasma viral load ≥12 months. Patients presenting any condition of risk for CVE were considered cases, and those without CVE risk conditions were controls. History of viral infections (Epstein-Barr virus, hepatitis C virus, hepatitis B virus, and cytomegalovirus), exposure to antiretroviral drugs, time since HIV diagnosis/under ART, and life style (demographics, weight, smoking, alcohol, and illicit drug use) were assessed. CD4/CD8 nadir and current counts, nadir and current CD4/CD8 ratio, immune activation markers (CD4CD38HLADR, CD8CD38HLADR), and serum levels of eight cytokines [IL-2, IL-4, IL-6, IL-10, tumoral necrosis factor-alpha (TNF-α), interferon gamma, macrophage inflammatory proteins 1 alpha, and interferon-inducing protein (IP-10)] were measured.
Results:
Two-thirds of patients were males. Cases (N = 106) were older (52.8 vs 49.5 years, p = 0.002), had higher levels of creatinine (0.97 vs 0.87 mg/dL, p = 0.002) and IL-6 (0.67 vs 0.52 pg/mL, p = 0.04) than controls (N = 114). There was no difference between groups regarding frequency of CD4CD39HLADR+ or CD8CD38HLADR+ cells. We found a significant correlation (all patients) between increased frequency of CD4CD38HLADR+ cells and levels of IP-10 (r = 0.171, p = 0.02) and TNF-α (r = 0.187, p = 0.01). Levels of IL-6 (r = 0.235, p = 0.02), TNF-α (r = 0.267, p = 0.01), and IP-10 (r = 0.205, p = 0.04) were correlated with CD4CD38HLADR+ cells, in controls. Higher frequency of CD4CD38HLADR+ cells was also correlated with levels of IP-10 (r = 0.271, p = 0.04) in patients presenting with arterial hypertension. Frequency of CD4CD38HLADR+ cells was negatively correlated with levels of IL-2 (r = -0.639, p = 0.01) and IL-6 (r = -0.0561, p = 0.03) in patients with hypercholesterolemia. No association was detected between viral infections or smoking/alcohol use and immune activation markers.
Conclusion:
Our results indicate IL-6 levels are associated with increased CV risk. Activated CD4+ T cells were associated with increased levels of proinflammatory cytokines.
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