Low serum phosphate levels are related to increased cardiovascular risk in HIV-1 infected patients

Purpose of the study Hypophosphatemia may contribute directly to the devel- opment of obesity, hypertension and dyslipidemia. Hyperglycemia, insulin resistance, hyperlipidemia and hypertension, which are components of metabolic syn- drome, are also recognized as strong risk factors for car- diovascular disease [1]. This study was performed to determine whether serum phosphate levels are asso- ciated with increased risk for cardiovascular events. Methods We enrolled 125 consecutive HIV-1-infected patients in a cross-sectional study. All patients were receiving highly active antiretroviral therapy (HAART) for more than six months. Fasting phosphate, lipids (cholesterol, HDL, triglycerides), Homeostasis Model Assessment (HOMA), blood pressure were evaluated. Framingham 10 years risk of general cardiovascular disease was used to assess three cardiovascular risk (CVR) categories (low CVR 20%). Summary of results We observed a statistically significant decrease in serum phosphate levels in the three different CVR groups (low risk: 3.5 mg/dl; medium risk: 3.3 mg/dl; high risk: 2.9 mg/dl; p=0.001). There was a strong negative correlation between Framingham score and phosphate levels (r:- 0.37, p<0.0001). Figure 1 Multiple regression analysis, including age, months of HAART, CD4 cells count, cholesterol, HDL, HOMA, systolic pressure, months of Tenofovir use, showed that only HOMA (r:-0.30, p<0.01) and age (r:-0.3, p<0.01) were the most important determinants of serum phos- phate values. Conclusions We found that lower phosphate level is correlated with cardiovascular risk and insulin resistance. Therefore, when serum phosphate levels are too low the patients is at risk for cardiovascular events and/or metabolic syndrome

Persistence of attenuated HIV-1 rev alleles in an epidemiologically linked cohort of long-term survivors infected with nef-deleted virus

<p>Abstract</p> <p>Background</p> <p>The Sydney blood bank cohort (SBBC) of long-term survivors consists of multiple individuals infected with <it>nef</it>-deleted, attenuated strains of human immunodeficiency virus type 1 (HIV-1). Although the cohort members have experienced differing clinical courses and now comprise slow progressors (SP) as well as long-term nonprogressors (LTNP), longitudinal analysis of <it>nef</it>/long-terminal repeat (LTR) sequences demonstrated convergent <it>nef</it>/LTR sequence evolution in SBBC SP and LTNP. Thus, the <it>in vivo </it>pathogenicity of attenuated HIV-1 strains harboured by SBBC members is dictated by factors other than <it>nef</it>/LTR. Therefore, to determine whether defects in other viral genes contribute to attenuation of these HIV-1 strains, we characterized dominant HIV-1 <it>rev </it>alleles that persisted in 4 SBBC subjects; C18, C64, C98 and D36.</p> <p>Results</p> <p>The ability of Rev derived from D36 and C64 to bind the Rev responsive element (RRE) in RNA binding assays was reduced by approximately 90% compared to Rev derived from HIV-1_NL4-3, C18 or C98. D36 Rev also had a 50–60% reduction in ability to express Rev-dependent reporter constructs in mammalian cells. In contrast, C64 Rev had only marginally decreased Rev function despite attenuated RRE binding. In D36 and C64, attenuated RRE binding was associated with rare amino acid changes at 3 highly conserved residues; Gln to Pro at position 74 immediately N-terminal to the Rev activation domain, and Val to Leu and Ser to Pro at positions 104 and 106 at the Rev C-terminus, respectively. In D36, reduced Rev function was mapped to an unusual 13 amino acid extension at the Rev C-terminus.</p> <p>Conclusion</p> <p>These findings provide new genetic and mechanistic insights important for Rev function, and suggest that Rev function, not Rev/RRE binding may be rate limiting for HIV-1 replication. In addition, attenuated <it>rev </it>alleles may contribute to viral attenuation and long-term survival of HIV-1 infection in a subset of SBBC members.</p

Altered phosphate metabolism in HIV-1-infected patients: another feature of metabolic syndrome?

Purpose of the study Metabolic syndrome represent a cluster of cardiovascu- lar risk factors that has become a serious problem for HIV-1-infected patients. It was proposed that distur- bances in phosphate metabolism may represent a key feature of metabolic syndrome. Because phosphate is involved directly in carbohydrate metabolism, hypopho- sphatemia can results in impaired utilization of glucose, insulin resistance and hyperinsulinemia. Thus, we undertook the present study to investigate the relation- ship between phosphate levels and the presence of the characteristics of metabolic syndrome, as well as the mechanism that may be responsible for reduced phos- phate levels in patients with this syndrome. Methods 130 HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single centre study. All patients were receiving HAART for more than six months. We selected two groups: HIV+ patients with metabolic syndrome (group A, n=86) and HIV+ patients without metabolic syndrome (group B, n=44). The diag- nosis of metabolic syndrome was based on Adult Treat- ment Panel III guidelines. Demographic characteristics, metabolic variables, duration of Tenofovir therapy, dura- tion of HAART, CD4 and viral load were collected. Kid- ney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. Summary of results Patients with metabolic syndrome showed significantly lower phosphate (3.13 mg/dl vs 3.55 mg/dl, p<0.01) and higher insulin (13.2 mg/dl vs 6.9 mg/dl, p<0.01) levels compared with controls. There was a linear significant decrease in phosphate values as the number of compo- nents of metabolic syndrome increased (p<0.001). Multi- ple regression analysis including all 5 components of metabolic syndrome and months of TDF treatment showed that insulin level was the most discriminant of serum phosphate (r= -0.22, p<0.01). Figure 1 Conclusions Our preliminary data demonstrated that HIV-1-infected patients with metabolic syndrome showed significantly lower phosphate levels compared with HIV-1-infected patients without metabolic syndrome regardless of teno- fovir based therapy. The clinical significance of these disturbances, as well as their importance as target for preventive or therapeutic interventions, remains to be established

Kidney tubular function and serum phosphate levels in HIV-1-infected patients treated with tenofovir: preliminary results

Purpose of the study There is concern that human immunodeficiency virus (HIV) infection and the use of highly active antiretro- viral therapy lead to cumulative toxicity. Tenofovir (TDF) is the first choice for most subjects. Even if it has a safe metabolic profile, much attention has been fixed on kidney tubular function and regulation of phosphate metabolism. We performed this study to evaluate the role of a TDF based regimen has on renal tubular over time. Methods Prospective, cross-sectional, single centre study was car- ried out. 121 HIV-1-infected patients were consecutively enrolled in six groups based on duration of TDF exposi- tion: G0, from 6 to 12 months; G1 from 13 to 24 months; G2 from 25 to 36 months; G3 from 37 to 48 months; G4 more than 48 months and G5 under HAART but never exposed to TDF. Glomerular func- tion was assessed using creatinine clearance (CrCL) cal- culated by MDRD. Tubular function was assessed using fractional excretion ratio of phosphate and normalized renal threshold phosphate concentration. Demographic, CD4, serum phosphate levels, viral load were collected. Summary of results A total of 121 consecutive HIV-1-infected patients were analyzed: 15 in G0, 11 in G1, 14 in G2, 32 in G3, 35 in G4 and 14 in G5. Mean of TDF exposure was 10.26, 21.4, 36.2, 47.3 and 67.4 months in G0, G1, G2, G3 and G4 respectively. There was no statistically significant dif- ference of mean values of FEP(11.2, 10.3, 8.4, 9.8, 11.1 and 10% in G0, G1, G2, G3, G4 and G5 respectively), TmPO4/GFR (3.5, 3.5, 3.6, 3.6, 3.4 and 3.4 mg/dl in G0, G1, G2, G3, G4 and G5 respectively ), CrCL (102.2, 94.3, 92.9, 106.5, 103.1 and 101.6 ml/min/1.73m2 in G0, G1, G2, G3, G4 and G5 respectively) and serum phos- phate levels (3.4, 3.3, 3.1, 3.5, 3.3 and 3.4 in G0, G1, G2, G3, G4 and G5 respectively) between groups. Moreover, we did not find correlation of FEP (r:0.04, p:0.6) and TmPO4/GFR (r:0.05, p:0.5) with duration of TDF therapy. Conclusions Treatment with TDF is not associated with altered kid- ney tubular function and serum phosphate levels over time

Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790

Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients

<p>Abstract</p> <p>Background</p> <p>The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality.</p> <p>Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome) is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease.</p> <p>The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease in HIV-1 infected patients.</p> <p>Methods</p> <p>We enrolled 88 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively.</p> <p>Results</p> <p>The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p < 0.0001 and p < 0.001, respectively). Using the average OARI as the dependent variable, total serum cholesterol level, HDL, triglycerides, glycemia, sex, blood pressure, age and PRFT were independent factors associated with OARI. A PRFT of 6.1 mm was the most discriminatory value for predicting an OARI > 0.74 (sensitivity 78.9%, specificity 82.8%).</p> <p>Conclusions</p> <p>Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients.</p

Schistosomiasis Research in the Dongting Lake Region and Its Impact on Local and National Treatment and Control in China

Schistosomiasis is a chronic and debilitating parasitic disease that has often been neglected because it is a disease of poverty, affecting poor rural communities in the developing world. This is not the case in the People's Republic of China (PRC), where the disease, caused by Schistosoma japonicum, has long captured the attention of the Chinese authorities who have, over the past 50–60 years, undertaken remarkably successful control programs that have substantially reduced the schistosomiasis disease burden. The Dongting Lake region in Hunan province is one of the major schistosome-endemic areas in the PRC due to its vast marshland habitats for the Oncomelania snail intermediate hosts of S. japonicum. Along with social, demographic, and other environmental factors, the recent completion and closure of the Three Gorges dam will most likely increase the range of these snail habitats, with the potential for re-emergence of schistosomiasis and increased transmission in Hunan and other schistosome-endemic provinces being a particular concern. In this paper, we review the history and the current status of schistosomiasis control in the Dongting Lake region. We explore the epidemiological factors contributing to S. japonicum transmission there, and summarise some of the key research findings from studies undertaken on schistosomiasis in Hunan province over the past 10 years. The impact of this research on current and future approaches for sustainable integrated control of schistosomiasis in this and other endemic areas in the PRC is emphasised