Emma Wainwright

Comprehensive Cardiac Magnetic Resonance Imaging and Spectroscopy Reveal a High Burden of Myocardial Disease in HIV Patients

Background— HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy. Methods and Results— Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels (P <0.003) and 74% higher median plasma triglyceride levels (both P<0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects (P<0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders. Conclusions— Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.

United Kingdom National Guideline on the Management of Trichomonas vaginalis 2014

The main objective is to assist practitioners in managing men and women diagnosed with Trichomonas vaginalis (TV) infection. This guideline offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of TV, covering the management of the initial presentation, as well as how to prevent transmission and future infection.

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called “beneficial” regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control.

HIV-1–Related Cardiovascular Disease Is Associated With Chronic Inflammation, Frequent Pericardial Effusions, and Probable Myocardial Edema

Background—Patients with treated HIV infection have clear survival benefits although with increased cardiac morbidity and mortality. Mechanisms of heart disease may be partly related to untreated chronic inflammation. Cardiovascular magnetic resonance imaging allows a comprehensive assessment of myocardial structure, function, and tissue characterization. We investigated, using cardiovascular magnetic resonance, subclinical inflammation and myocardial disease in asymptomatic HIV-infected individuals. Methods and Results—Myocardial structure and function were assessed using cardiovascular magnetic resonance at 1.5-T in treated HIV-infected individuals without known cardiovascular disease (n=103; mean age, 45±10 years) compared with healthy controls (n=92; mean age, 44±10 years). Assessments included left ventricular volumes, ejection fraction, strain, regional systolic, diastolic function, native T1 mapping, edema, and gadolinium enhancement. Compared with controls, subjects with HIV infection had 6% lower left ventricular ejection fraction (P<0.001), 7% higher myocardial mass (P=0.02), 29% lower peak diastolic strain rate (P<0.001), 4% higher short-tau inversion recovery values (P=0.02), and higher native T1 values (969 versus 956 ms in controls; P=0.01). Pericardial effusions and myocardial fibrosis were 3 and 4× more common, respectively, in subjects with HIV infection (both P<0.001). Conclusions—Treated HIV infection is associated with changes in myocardial structure and function in addition to higher rates of subclinical myocardial edema and fibrosis and frequent pericardial effusions. Chronic systemic inflammation in HIV, which involves the myocardium and pericardium, may explain the high rate of myocardial fibrosis and increased cardiac dysfunction in people living with HIV.

HIV is an independent predictor of aortic stiffness

BackgroundPatients with treated Human Immunodeficiency Virus-1 (HIV) infection are at increased risk of cardiovascular events. Traditionally much of this risk has been attributed to metabolic and anthropometric abnormalities associated with HIV, which are similar to the metabolic syndrome (MS), an established risk factor for cardiovascular mortality. It remains unclear whether treated HIV infection is itself associated with increased risk, via increase vascular stiffness.Methods226 subjects (90 with HIV) were divided into 4 groups based on HIV and MS status: 1) HIV-ve/MS-ve, 2) HIV-ve/MS + ve, 3) HIV + ve/MS-ve and 4)HIV + ve/MS + ve. CMR was used to determine aortic pulse wave velocity (PWV) and regional aortic distensibility (AD).ResultsPWV was 11% higher and regional AD up to 14% lower in the HIV + ve/MS-ve group when compared to HIV-ve/MS-ve (p < 0.01 all analyses). PWV and AD in the HIV + ve/MS-ve group was similar to that observed in the HIV-ve/MS + ve group (p > 0.99 all analyses). The HIV + ve/MS + ve group had 32% higher PWV and 30-34% lower AD than the HIV-ve/MS-ve group (all p < 0.001), and 19% higher PWV and up to 31% lower AD than HIV + ve/MS-ve subjects (all p < 0.05). On multivariable regression, age, systolic blood pressure and treated HIV infection were all independent predictors of both PWV and regional AD.ConclusionAcross multiple measures, treated HIV infection is associated with increased aortic stiffness and is also an independent predictor of both PWV and regional AD. The magnitude of the effect of treated HIV and MS are similar, with additive detrimental effects on central vascular elasticity.

Hypophosphataemia with non-tenofovir-containing antiretroviral therapy.

Summary Hypophosphataemia with tenofovir (TDF) treatment has been well described. The role of HIV infection and of other antiretroviral (ART) agents in hypophosphataemia has received less attention. The aim of this study was to determine the prevalence of hypophosphataemia in HIV-positive adults. We measured the fasting plasma phosphate level and estimated glomerular filtration rate (eGFR) in 123 HIV-positive patients. A total of 26% had hypophosphataemia and 11% had hypophosphataemia of grades 2–4 (0.65 mmol/L or less). Hypophosphataemia of any grade was more frequent in those who were ART-treated than ART-naive (35% versus 10%; P = 0.0001). Multiple linear regression analysis showed no significant association between phosphate level and gender, TDF status, duration of ART, duration of HIV infection and eGFR. Increasing age was significantly associated with a very small rise in phosphate level. Isolated hypophosphataemia was significantly more frequent in HIV-positive subjects receiving ART than ART-naive individuals, irrespective of the drug regimen.

Comprehensive cardiac magnetic resonance imaging and spectroscopy reveals a high burden of myocardial disease in HIV infection

Background Human immunodeficiency virus (HIV) infection continues to be endemic worldwide. Whilst treatments are successful, it remains controversial whether patients receiving optimal therapy for HIV infection have structural, functional or biochemical cardiac abnormalities which may underlie the increased cardiac morbidity and mortality. Our main objective was to characterise myocardial abnormalities in a contemporary group of HIV-infected individuals.