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

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.

Increased expression of CD38 and HLADR in HIV-infected patients with oral lesion.

Persistent immune actiation is associated with innadequate immune recovery in HIV-patients. This study assessed the relationship between frequency of expression of cell activation markers (CD38 and HLADR) and presence of oral lesions in HIV-1 infected patients. Fifty-seven HIV-infected persons, undergoing antiretroviral treatment, were divided into three groups, according to the number of CD4+ T cells and CD4+ /CD8+ ratio: adequate, partial, and inadequate immune restauration. All patients underwent full mouth assessments for saliva flow measurement, oral mucosal lesion, periodontal disease, and severity of periodontitis. Immune activation markers levels were compared according to three groups of periodontal disease ("No periodontal disease," "gingivitis," and "periodontitis"). Oral mucosal lesions (P = 0.03) and peridodontal disease (P = 0.03) were associated with lower CD4+ /CD8+ ratio. Patients with oral mucosal lesions had significantly higher median levels of HLADR and CD38 markers in all T-lymphocytes populations than patients without oral lesions. Patients with gingivitis and with periodontitis presented significantly higher median levels of CD3+ HLADR+ , CD4+ HLADR+ , CD8+ HLADR+ , and CD3+ CD38+ and significantly lower CD4+ /CD8+ ratio than patients with no periodontal disease. Increased levels of HLADR and CD38 expressions in peripheral blood were associated with oral lesions in HIV-positive patients. Periodontal disease was associated with HLADR expression.

Coinfection by Hepatitis C Is Strongly Associated with Abnormal CD4/CD8 Ratio in HIV Patients under Stable ART in Salvador, Brazil.

UNLABELLED: Proper immune restoration (CD4 count >500 and normal CD4/8 ratio) is reached only by a fraction of HIV patients, despite stable viral suppression. METHODS: We present a case-control study to compare HIV patients with viral suppression >1 year, according to immune restoration pattern: adequate response (AR) defined by CD4 > 500 cells/mm(3) and CD4/8 ratio >1; partial response (PR = patients with CD4 > 500, but CD4/8 ratio <1); inadequate response (IR = CD4 < 500 cells). RESULTS: We evaluated 293 consecutive patients (89 AR, 112 PR, and 92 IR), 70% males. Male gender (p < 0.01), lower mean CD4 nadir (p < 0.001), higher baseline VL (p = 0.01), previous diagnosis of Tb (p = 0.03), or HCV (p < 0.01) was associated with IR. Likelihood of AR/PR was similar regardless of gender, after adjusting for nadir CD4+ cells count. Longer time under suppressive ART was also associated with a greater chance of AR, but logistic regression identified coinfection by HCV as the main factor associated with abnormal CD4/CD8 ratio. CONCLUSION: Early initiation of ART and longer time since first undetectable PVL were predictors of AR. Previous HCV diagnosis significantly increases the risk of abnormal CD4/CD8 ratio.