Therapies that halt progression of chronic hepatitis B virus (HBV) and achieve a cure for chronic hepatitis C virus (HCV) have encouraged development of innovative strategies to diagnose and link ...patients to care. We describe the prevalence and risk factors for HBV and HCV infections and use of an opt-out hepatitis testing and integrated linkage to care pathway in a London Emergency Department (ED). ED patients aged ≥16 years having routine blood tests from 15 February-28 March 2016 were tested for hepatitis, unless opted out. Hepatitis B surface antigen (HBsAg) and hepatitis C antibody tests (HCV-Ab, including a confirmatory hepatitis C antigen test (HCV-Ag)) were pre-selected on electronic blood test requests. Linkage to care (attending one clinic appointment) was offered to HBsAg and HCV-Ag patients (new or known-disengaged with care diagnoses). Weighted prevalence estimates and risk factors for seropositivity adjusted by demographics and survey weights were calculated using logistic regression. Hepatitis testing uptake was 56% (3,290/5,865). Overall, 26 HBsAg (10 new diagnoses) and 63 HCV-Ab patients were identified of which 32 were HCV-Ag positive (10 new diagnoses). Weighted seroprevalence of HBsAg was 0.50% (95% CI 0.3-0.8%); HCV-Ab 2.0% (95% CI 1.5-2.7%) and HCV-Ag 1.2% (95% CI 0.8-1.7%). Risk factors for infection were being male (HBsAg: aOR 4.1, 95% CI 1.5-11.3), of non-White British ethnicity (HBsAg: aOR>11) or being homeless (HCV-Ag: aOR 18.9, 95% CI 6.9-51.4). We achieved a high linkage to care uptake for HBsAg (93%) and HCV-Ag (78%) among patients who were contacted and required linkage. A pre-selected hepatitis testing ordering system facilitated a high testing uptake. New and disengaged with care diagnoses and a high HCV prevalence were identified demonstrating the potential to identify and link patients to care in this setting. Strategies connecting clinical care with community outreach services are key for improving patient linkage to care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Over the past decade the developments made in treating people with human immune deficiency virus (HIV) have greatly improved quality of life and life expectancy. However, the nature of asymptomatic ...HIV-associated minor neurocognitive disorder (HAND) remains unclear. In this study we explored the occurrence of neuropsychological and neuroimaging changes in medically and psychiatrically stable HIV-1 infected patients on highly active antiretroviral treatment (HAART) from two separate age groups.
Participants included 20 HIV-1 infected younger (aged 20–40) and 20 HIV-1 older patients (aged 50–75). Comparisons were made with 20 age- and education-matched younger and 22 matched older healthy seronegative males. Participants were stable on treatment and asymptomatic at study onset with undetectable HIV-1 viral loads, and free of medical or psychiatric co-morbidity, alcohol or substance misuse. A detailed neuropsychological assessment was used and volumetric-magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) performed to assess grey and white-matter integrity.
We found significant effects of ageing on memory, grey and white matter measures. Comparison of the HIV-positive and HIV-negative groups did not show significant differences on the neuropsychological tests after Bonferroni correction, and there were no significant age by HIV status interactions. However, we did find reduced grey matter volume on MRI in our HIV-positive participants within the medial and superior frontal gyri. We also found significant ageing effects in fronto-temporal grey and white matter, independent of the effect of HIV.
The results from this study suggest that HIV-1 disease by itself does not significantly impair cognitive function when patients are otherwise asymptomatic. Nevertheless, the imaging techniques were sensitive enough to detect subtle grey matter changes not normally evident until much later in the disease. If confirmed in a longitudinal study this frontal grey matter change could represent an important biomarker for trials in HIV disease.
Short duration treatment may aid HCV elimination among key populations. This study evaluated the efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection.
In this ...single-arm multicentre international trial, adults with recent HCV (duration of infection <12 months) received glecaprevir-pibrentasvir 300 mg-120 mg daily for 4 weeks. Primary infection was defined as a first positive anti-HCV antibody and/or HCV RNA measurement within 6 months of enrolment and either acute clinical hepatitis within 12 months (symptomatic illness or alanine aminotransferase >10x the upper limit of normal) or antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months and prior clearance (spontaneous or treatment). The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) and per-protocol (PP) populations.
Twenty-three participants (96% men, 70% HIV, 57% ever injected drugs) received treatment, of whom 74% had genotype 1a infection and 35% recent reinfection. At baseline, median duration of infection was 17 weeks (IQR 11–29) and HCV RNA was 5.8 log10IU/ml (IQR 5.2–6.9). SVR12 was achieved by 78% (18/23; 95% CI 56–93%) and 82% (18/22; 95% CI 60–95%) of the ITT and PP populations, respectively, and in 100% (12/12; 95% CI 74–100%) of participants with baseline HCV RNA ≤6 log10. There were four cases of virological failure (relapse); three received retreatment with 12 weeks sofosbuvir-velpatasvir or grazoprevir-elbasvir (SVR, n = 2; loss to follow-up, n = 1). No serious adverse events were reported.
While most achieved SVR, the efficacy of a 4-week regimen of glecaprevir-pibrentasvir was lower than observed with longer treatment durations (≥6 weeks) among people with recent HCV.
Clinicaltrials.gov Identifier: NCT02634008.
Short duration treatment may aid HCV elimination among key populations. This investigator-initiated single-arm multicentre international pilot trial demonstrated that efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection was sub-optimal (SVR12 78% ITT, 82% PP). Baseline HCV RNA appeared to impact response, with higher efficacy among participants with lower baseline HCV RNA (≤6 log10; SVR12 100% ITT, 12/12). While most achieved SVR, the efficacy of 4 weeks of glecaprevir-pibrentasvir was below that seen with longer treatment durations (≥6 weeks).
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•We evaluated the efficacy of 4 weeks’ glecaprevir-pibrentasvir in people with recent HCV infection.•SVR12 was achieved in 78% and 82% of the ITT and PP populations, respectively, and in 100% with baseline HCV RNA ≤6 log10.•There were four cases of virological failure (relapse).•The efficacy of 4 weeks’ glecaprevir-pibrentasvir was lower than observed with longer treatment durations (≥6 weeks).
Purpose
To evaluate the utility of
18
F-FDG PET/CT in suspected cerebral pathology in HIV-infected individuals.
Methods
18
F-FDG PET/CT scans from 29 HIV-infected individuals (29 brain scans, 22 ...whole-body scans) who presented with neurological symptoms and signs were retrospectively reviewed and compared with subsequent clinical investigations.
Results
The majority of patients (
n
= 25) were referred to differentiate infection from malignant causes of cerebral pathology. Ten of the 11 patients with an eventual diagnosis of toxoplasmosis infection were correctly diagnosed by
18
F-FDG PET/CT showing lesional uptake less than that of normal brain cortex (mean SUVmax 3.5, range 1.9 – 5.8). All five patients with a final diagnosis of primary central nervous system lymphoma (PCNSL) were correctly diagnosed by
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F-FDG PET/CT showing lesional uptake greater than that of normal brain cortex (mean SUVmax 18.8, range 12.4 – 29.9). Four of the five patients with
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F-FDG PET/CT features suggesting a vasculitic process had vasculitis confirmed as the final diagnosis. Three patients showed variable uptake in multiple cerebral lesions (including final diagnoses of tuberculosis and metastases from lung cancer in two patients) and there were four other miscellaneous diagnoses. In 12 patients biopsies were performed at sites guided by PET abnormality (7 brain, 5 lymph nodes) confirming or excluding significant disease in 11.
Conclusion
18
F-FDG PET/CT is particularly useful for differentiating between infection and PCNSL in HIV-infected patients with a cerebral lesion on MRI or CT.
18
F-FDG PET/CT was also a helpful tool in the diagnostic work-up of patients with other HIV-related cerebral pathology. Additional advantages of
18
F-FDG PET/CT are the abilities to assess abnormally increased glucose metabolism in the body and to identify potential sites for biopsy.
To determine comparative fracture risk in HIV patients compared with uninfected controls.
A randomised cross-sectional study assessing bone mineral density (BMD), fracture history and risk factors in ...the 2 groups.
Hospital Outpatients.
222 HIV infected patients and an equal number of age-matched controls.
Fracture risk factors were assessed and biochemical, endocrine and bone markers measured. BMD was assessed at hip and spine. 10-year fracture probability (FRAX) and remaining lifetime fracture probability (RFLP) were calculated.
BMD, and history of fractures.
Reported fractures occurred more frequently in HIV than controls, (45 vs. 16; 20.3 vs. 7%; OR=3.27; p=0.0001), and unsurprisingly in this age range, non-fragility fractures in men substantially contributed to this increase. Osteoporosis was more prevalent in patients with HIV (17.6% vs. 3.6%, p<0.0001). BMD was most reduced, and predicted fracture rates most increased, at the spine. Low BMD was associated with antiretroviral therapy (ART), low body mass index and PTH. 10-year FRAX risk was <5% for all groups. RLFP was greater in patients with HIV (OR=1.22; p=0.003) and increased with ART (2.4 vs. 1.50; OR= 1.50; p=0.03).
The increased fracture rate in HIV patients in our relatively youthful population is partly driven by fractures, including non-fragility fractures, in men. Nonetheless, these findings may herald a rise in osteoporotic fractures in HIV patients. An appropriate screening and management response is required to assess these risks and identify associated lifestyle factors that are also associated with other conditions such as cardiovascular disease and diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to ...investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.
A case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) using a (11)C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling.
Twenty-four aHCV cases completed NCT and (1)H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent (1)H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on (1)H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in (11)C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations.
Poorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher (11)C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Is it all cerebral toxoplasmosis? Mentzer, Alex, Dr; Perry, Melissa, MRCP; Fitzgerald, Naomi, MRCP ...
The Lancet (British edition),
01/2012, Letnik:
379, Številka:
9812
Journal Article
Recenzirano
Primary cerebral lymphoma is uncommon, but over 30% of cases are associated with HIV infection.1 Diff erentiation of the two pathologies is diffi cult owing to the similar clinical and radiological ...presentation, but MRI and PET are the imaging modalities of choice, and tissue diagnosis is the gold standard.2,3 Prognosis in HIV-infected patients with primary cerebral lymphoma is poor, with median survival of 2 months, but antiretroviral therapy may improve life expectancy.4 The choice of chemotherapy tends to be a methotrexate-based regimen with a combination of other agents such as vincristine or cytarabine.4 This case serves as a reminder of the complexity of patients with late presentation of HIV infection in the UK, where the Health Protection Agency estimates that around 30% of individuals with HIV infection are undiagnosed and a similar percentage of those diagnosed present late.5 The HIV-infected population is predicted to reach 100 000 by 2012, therefore, the proportion of undiagnosed patients and late presenters must be reduced.
Dr. Tsiakalos should be listed as the ninth author and affiliated with Third Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece. (2013) ...Correction: A Cross-Sectional Randomised Study of Fracture Risk in People with HIV Infection in the Probono 1 Study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Background: The introduction of highly active antiretroviral therapy (HAART) around 1996 markedly reduced mortality and morbidity from human immunodeficiency virus (HIV) infection. As life ...expectancy has improved, the chronic complications of HIV and HAART have become increasingly relevant.
Scope: This article provides an overview of the HIV-associated lipodystrophy, its pathogenesis and its clinical consequences (based on a search strategy in PubMed including literature published to November 2007).
Findings: Lipodystrophy syndrome is characterized by abnormal fat distribution syndrome associated with metabolic disturbances and includes insulin resistance, deranged glucose and lipid metabolism. It is associated with increased risks of progression to type 2 diabetes and cardiovascular disease. Robust diagnostic criteria are required for lipodystrophy, and subsequent prospective cohort studies and randomized controlled trials are then required to determine the etiology and prognosis of lipodystrophy, and to evaluate therapeutic interventions for this consequence of HAART. Therapies to improve insulin resistance have been tried but they are frequently ineffective, and are limited by potential toxicity in this population. Hence, current management options for HIV associated lipodystrophy are limited and are mostly based on avoidance of risk factors and switching of antiretroviral drugs.
Conclusion: As the '3 by 5 strategy' of providing HIV drugs to the developing world is implemented worldwide, the numbers of patients adhering to antiretroviral medicines is dramatically increasing. One must be aware that in reducing the burden of acute retroviral disease, the treatments proposed might lead to significant rates of metabolic complications and further exacerbation of the epidemic of diabetes and cardiovascular disease.
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