Immune Activation, Proinflammatory Cytokines, and Conventional Risks for Cardiovascular Disease in HIV Patients: A Case-Control Study in Bahia, Brazil

Abstract

BackgroundCardiovascular 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.MethodsWe 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.ResultsTwo-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.ConclusionOur results indicate IL-6 levels are associated with increased CV risk. Activated CD4+ T cells were associated with increased levels of proinflammatory cytokines.

CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection

“…Interestingly, plasma levels of CXCL13 were also associated with CMV co-infection which was reported to be a contributor to HIV-associated systemic inflammation (39). Immune activation is considered as a major factor contributing to the size of HIV reservoirs and development of non-AIDS events despite long-term ART (1, 4, 7). Therefore, therapeutic strategies targeting immune activation remains a priority for curing HIV infection.…”

“…Progressive CD4 T cell decline, elevated CD8 T cell counts, early damage to the intestinal mucosa, microbial translocation, CMV co-infection, and persistence of HIV in cellular reservoirs all contribute to systemic immune activation (2–6). Chronic immune activation and inflammation among PLWH on ART have been linked with increased risk for mortality and development of non-AIDS events such as cardiovascular dysfunction, renal failure, hepatic steatosis, neurocognitive degeneration, accelerated aging, and cancer (7, 8). Therefore, therapeutic strategies are needed to tackle residual immune activation to improve the quality of life of PLWH.…”

Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART

“…Consequently, HIV is now considered a chronic disease, rather than a fatal one, in countries where ART is available [2]. The persistence of the virus supports a chronic status of immune activation and inflammation leading to the increased production of pro-inflammatory cytokines [3] and thymus dysfunction [4]. In addition, persistent inflammation exacerbates tissue damage in PLWH, particularly in the gastrointestinal tract, allowing microbial components to enter into circulatory system (microbial translocation), increasing inflammation [5].…”

A Noninvasive Prediction Model for Hepatitis B Virus Disease in Patients with HIV: Based on the Population of Jiangsu, China

“…Approximately 10% of HIV-infected people are also chronically coinfected with HBV [ 6 ]. Coinfected patients present with rapidly progressive liver disease, facing a higher risk of cirrhosis and even death [ 7 ]. HBV infection worsens the prognosis in HIV-positive people [ 6 ].…”