Circulating CD40 ligand, Dickkopf-1 and P-selectin in HIV-infected patients.

OBJECTIVES: The aim of this study was to evaluate the circulating levels of CD40 ligand (CD40 L), Dickkopf-1 (DKK-1) and P-selectin, their relationships and their contributions to cardiovascular risk in subjects with HIV infection. METHODS: The study population included 80 HIV-infected patients, 14 (17.5%) of whom had diabetes mellitus (DM) and 32 (40.0%) of whom had arterial hypertension (AH). The HIV-infected patients were compared with a control group with similar demographic and clinical features. CD40L, DKK-1 and P-selectin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The HIV-infected patients showed higher levels of all the cardiovascular disease (CVD) markers. Both serum CD40L and DKK-1 were significantly higher in HIV-infected patients than in the HIV-negative controls (P < 0.001), while soluble P-selectin showed no significant between-group difference (P = 0.133), reflecting the role of HIV infection in CVD. In the HIV-infected group, patients with DM showed lower levels of CD40L and DKK-1 in comparison with the nondiabetic patients and patients with AH (P < 0.05, with Bonferroni correction). In contrast, patients with AH showed higher levels of CD40L and DKK-1 in comparison to patients without DM or AH (P < 0.05, with Bonferroni correction). Patients with AH showed higher levels of CD40L and DKK-1 than patients with DM (P < 0.05, with Bonferroni correction). CONCLUSIONS: In this study, we found that HIV-infected patients displayed significantly higher circulating levels of both CD40L and DKK-1, which were linearly and directly correlated, when compared to HIV-negative patients. The presence of diabetes was associated with lower levels of both CD40L and DKK-1, whereas the presence of hypertension was associated with higher levels of CD40L.

Microalbuminuria and hypertension in HIV-infected patients: a preliminary study of telmisartan.

BACKGROUND: There is increasing evidence of hypertension and microalbuminuria in HIV-infected patients, and these are two important risk factors for renal and cardiovascular disease. Anti-hypertensive drugs inhibiting the renin-angiotensin system exert an antiproteinuric effect. Telmisartan, an angiotensin II receptor blocker and partial peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist that is approved for the treatment of hypertension, appears to exert a nephroprotective effect independent of blood pressure reduction in the general population. OBJECTIVE: The aim of this preliminary study was to evaluate possible nephroprotective effects of telmisartan in hypertensive HIV-positive patients with microalbuminuria. PATIENTS AND METHODS: Caucasian male patients with HIV infection (n=13) receiving stable combined antiretroviral therapy (without therapeutic changes for > 12 months) and a recent diagnosis of grade 1 hypertension were treated with daily oral telmisartan 80 mg for 6 months. Patients had suppressed viremia and a CD4 cell count > 300 cells/mL for 6 months, and microalbuminuria > 5 mg/dL. Systolic and diastolic blood pressure (SBP, DBP), triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), microalbuminuria, Modification of Diet Renal Disease-Glomerular Filtration Rate (MDRD-GFR), vascular endothelial growth factor (VEGF) and endothelin-1 were measured at baseline and at one, three and six months. All statistical analyses were performed using SAS 9.2. RESULTS: A significant reduction of microalbuminuria (p < 0.001) with stable MDRD-GFR was observed, although the main indices of renal function showed no substantial change. A significant reduction in mean SBP and DBP was observed at T1 and confirmed at T3 and T6 (SBP p < 0.001 and DBP p < 0.001), and there was BP normalization. Metabolic assessments showed an improvement in lipid parameters, and a significant decrease in insulin resistance assessed by the homeostasis model assessment index-insulin resistance (HOMA-IR) (p = 0.04). In addition, there was a statistically significant reduction in ESR (p = 0.02) and a non significant reduction in CRP. Other results included a significant reduction in serum VEGF and endothelin-1 levels (p < 0.001). CONCLUSIONS: From these preliminary findings, telmisartan has demonstrated efficacy in the control of hypertension and microalbuminuria in HIV-infected patients. Decreased microalbuminuria with stable MDRD-GFR may be indicative of a nephroprotective effect of telmisartan; mechanisms causing microalbuminuria in patients with HIV could be related to infection, chronic inflammation, and endothelial dysfunction. The decreased endothelin-1 and VEGF levels in patients in this study may be related to an endothelial protective effect of telmisartan. This study reports the first observation of renal and endothelial protective effects of telmisartan in HIV-positive patients.

Proteinuria in an African HIV-infected patient: effects of telmisartan.

Kidney disease remains a major comorbidity of HIV infection especially in subjects of African ethnicity. HIV-associated renal disease with overt proteinuria has been associated with poorer outcomes and increased mortality. Telmisartan, an angiotensin II receptor blocker partial agonist of the PPAR-? approved for the treatment of hypertension, seems to exert a nephro-protective effect independent of blood pressure reduction in the general population. But data are lacking in HIV-positive patients with proteinuria. A case is described of an HIV-positive African patient with severe proteinuria treated with telmisartan. This therapy allowed proteinuria to be improved. This case shows for the first time that therapy with telmisartan has renoprotective effects also in an African HIV-infected patient.

Beneficial effects of telmisartan in an HIV+ diabetic insulin-dependent patient.

In HIV-infected patients with metabolic disorders, as in the general population, there is evidence of hypertension requiring pharmacological treatment. The presence of diabetes constitutes a cluster of particularly high cardiovascular risks in patients, both regarding diabetic damage and hypertensive damage. We used telmisartan to manage high blood pressure values in an HIV-positive patient with insulin-dependent diabetes. Surprisingly, insulin therapy had to be suspended because of hypoglycemic fits and treatment with metformin was started. In conclusion, telmisartan was effective and well tolerated for the control of hypertension in this case and improved sensitivity to insulin. There are interesting effects of this drug in HIV-positive diabetic patients. Thus, if further studies confirm these effects, telmisartan may be the anti-hypertensive drug of first choice in HIV-infected subjects on combined antiretroviral therapy affected with diabetes and metabolic disorders.

Severe HIV-associated hypertriglyceridaemia treated with rosuvastatin plus omega-3 fatty acids.

Compared with healthy controls, HIV patients already have abnormal lipoprotein concentrations before the initiation of highly active antiretroviral therapy (HAART), which worsen with the therapy. HAART-associated dyslipidaemia features fundamental proatherogenic changes such as increased plasma triglycerides (TGs), increased total cholesterol and low-density lipoprotein cholesterol as well as decreased high-density lipoprotein cholesterol (HDL-C). The current guidelines for managing HIV-associated dyslipidaemia recommend diet and exercise counselling, alteration of HAART regimen or addition of lipid-lowering medications such as statins, fibrates and omega-3 (OM-3) fatty acids. Given that cardiovascular risk significantly increases with elevated lipid levels, selecting a drug to manage dyslipidaemia is particularly important. A case is described of an HIV patient who had severe hypertriglyceridaemia and bad metabolic parameters treated with rosuvastatin and OM-3 fatty acids. So we obtained a more marked reduction of TG levels than has never been described before in the literature, associated with a significant increase in HDL-C levels.

Acute urinary retention due to HSV-1: a case report.

Complications in urinary tract nervous routes due to herpes viruses as VZV and HSV-2 are well known. Acute urinary retention and chronic neuropathic pain are not rare when sacral dermatomes are involved by these viruses. However, an analogous condition has not yet been clearly ascribed to HSV-1 infection. We present a 32-year-old immunocompetent patient with fever, lumbar pain and acute urinary retention who had never had herpetic clinical manifestations. Urodynamic studies diagnosed a neurologic bladder with an absent filling sensation. Cystoscopic assessment revealed the presence of reddened and isolated small mucosal areas in the bladder walls. The search for herpes viruses in plasma and CSF by PCR assay were positive for HSV-1. After treatment with antiviral therapy the disease resolved. Intermittent catheterization was necessary and voiding dysfunction resolved after three weeks by its appearance. Neurological damage to the central nervous system (CNS) and/or PNS due to HSV-1 seems to be the most likely reason. The course of disease was benign and self-remitting.

Periodontitis and cytokine patterns in HIV positive patients.

OBJECTIVE: Oral and dental problems are common among human immunodeficiency virus (HIV) infected individuals, particularly the periodontitis is common in HIV-infected subjects. AIM: To evaluate the cytokine patterns in HIV+ patients with periodontitis. MATERIAL AND METHODS: In this study we analysed: HIV+ patients with and without periodontitis and HIV negative patients with and without periodontitis. The clinical periodontal evaluation was based on periodontal disease index and radiographic and clinical evidence of alveolar bone loss. The CD4- and CD8-T cell counts and the plasma viral load were measured. The Interferon (IFN)-gamma, Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-2, IL-4, IL-10 and IL-6 were evaluated by Cytometric Bead Array Assay and the IL-18 plasmatic levels were calculated by ELISA. RESULTS: The group of HIV+ with periodontitis shown levels of IL-2 and IL-18 statistically higher that the group of HIV+ without periodontitis. A positive correlation between the degree of the periodontitis and IFN-gamma, IL-2, IL-18 and CD8+ cells in the group of HIV+ with periodontitis has been shown. CONCLUSIONS: The results of the present study confirm that the IL-18, together with other cytokines, has a potential role in aetiopathogenesis of periodontitis in HIV+ patients.

Metabolic syndrome and cardiovascular risk in HIV-infected patients with lipodystrophy.

In this cross-sectional study, we evaluate potential predictors of Metabolic Syndrome (MS) in a group of 54 Caucasian chronically HIV-infected patients with lipodystrophy. According to ATP-III criteria, 22 patients were affected by MS and 32 were not. The mean age of the sample was 41.2+/-8.6 years, and most patients were males (74.1%); the two groups were homogeneous for gender, age, viro-immunologic status and the duration of antiviral therapy. The independent association between MS and several factors including demographic characteristics, type of highly-active antiviral therapy (HAART), viro-immunologic response, common cardiovascular risk factors (including Framingham scores), and selected cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10 and IL-18), was investigated using stepwise forward logistic regression. At multivariate analysis, the only independent predictors of the metabolic syndrome were triglycerides and IL-18. A 10 mg/dL increase in triglycerides corresponds to an adjusted risk ratio for MS of 1.11 (95 percent IC: 1.04-1.19); and patients in the top tertile of IL-18 (those with IL-18 >/= 530 pg/L) had more than three times the likelihood of MS, as compared to the bottom and medium tertiles of IL-18 (patients with IL-18< 530 pg/L). This relationship was not attenuated by the inclusion of any other variable in the multivariate model. However, the association between metabolic syndrome and IL-18 is no longer significant when IL-18 is treated as a continuous variable (trend p = 0.087). Our results on HIV patients with lipodystrophy confirm previous findings on a strong independent association between IL-18 and MS in the general population. Further research is needed to clarify the mechanism of this association and its role in the development of cardiovascular disease in HIV patients.