No Changes in Human Immunodeficiency Virus (HIV) Suppression and Inflammatory Markers in Cerebrospinal Fluid in Patients Randomly Switched to Dolutegravir Plus Lamivudine (Spanish HIV/AIDS Research Network, PreEC/RIS 62)

A major concern of HIV dual therapy is a potential lower efficacy in viral reservoirs, especially in the central nervous system (CNS). We evaluated HIV RNA, neuronal injury and inflammatory biomarkers and dolutegravir (DTG) exposure in cerebrospinal fluid (CSF) in patients switching to DTG+lamivudine (3TC). All participants maintained viral suppression in plasma and CSF at week 48. We observed no increase in CSF markers of inflammation or neuronal injury. Median (IQR) total and unbound DTG in CSF were 7.3(5.9-8.4) ng/mL and 1.7(1.2-1.9) ng/mL, respectively. DTG+3TC may maintain viral control without changes in inflammatory/injury markers within the CNS reservoir

Education and wealth inequalities in healthy ageing in eight harmonised cohorts in the ATHLOS consortium: a population-based study

Background: The rapid growth of the size of the older population is having a substantial effect on health and social care services in many societies across the world. Maintaining health and functioning in older age is a key public health issue but few studies have examined factors associated with inequalities in trajectories of health and functioning across countries. The aim of this study was to investigate trajectories of healthy ageing in older men and women (aged ≥45 years) and the effect of education and wealth on these trajectories. Methods: This population-based study is based on eight longitudinal cohorts from Australia, the USA, Japan, South Korea, Mexico, and Europe harmonised by the EU Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. We selected these studies from the repository of 17 ageing studies in the ATHLOS consortium because they reported at least three waves of collected data. We used multilevel modelling to investigate the effect of education and wealth on trajectories of healthy ageing scores, which incorporated 41 items of physical and cognitive functioning with a range between 0 (poor) and 100 (good), after adjustment for age, sex, and cohort study. Findings: We used data from 141 214 participants, with a mean age of 62·9 years (SD 10·1) and an age range of 45–106 years, of whom 76 484 (54·2%) were women. The earliest year of baseline data was 1992 and the most recent last follow-up year was 2015. Education and wealth affected baseline scores of healthy ageing but had little effect on the rate of decrease in healthy ageing score thereafter. Compared with those with primary education or less, participants with tertiary education had higher baseline scores (adjusted difference in score of 10·54 points, 95% CI 10·31–10·77). The adjusted difference in healthy ageing score between lowest and highest quintiles of wealth was 8·98 points (95% CI 8·74–9·22). Among the eight cohorts, the strongest inequality gradient for both education and wealth was found in the Health Retirement Study from the USA. Interpretation: The apparent difference in baseline healthy ageing scores between those with high versus low education levels and wealth suggests that cumulative disadvantage due to low education and wealth might have largely deteriorated health conditions in early life stages, leading to persistent differences throughout older age, but no further increase in ageing disparity after age 70 years. Future research should adopt a lifecourse approach to investigate mechanisms of health inequalities across education and wealth in different societies. Funding: European Union Horizon 2020 Research and Innovation Programme.The ATHLOS project was funded by the European Union Horizon 2020 Research and Innovation Programme (grant number 635316). This study was supported by the 5-year ATHLOS projec

Cohort profile: The Ageing Trajectories of Health – Longitudinal Opportunities and Synergies (ATHLOS) project

This project, Ageing Trajectories of Health – Longitudinal Opportunities and Synergies (ATHLOS), funded by the European Union’s Horizon 2020 Research and Innovation Program, aims to achieve a better understanding of the impact of ageing on health by developing a new single measure of health status. With this measure, the project intends to identify patterns of healthy ageing trajectories and their determinants, the critical points in time when changes in trajectories are produced, and to propose timely clinical and public health interventions to optimize and promote healthy ageing. To achieve this, a new cohort has been composed from harmonized datasets of existing international longitudinal cohorts related to health and ageing

HTLV-1 infection in solid organ transplant donors and recipients in Spain

Background: HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. Methods: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. Results: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. Conclusion: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopath

Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain

Development of a common scale for measuring healthy ageing across the world: results from the ATHLOS consortium

Background: Research efforts to measure the concept of healthy ageing have been diverse and limited to specific populations. This diversity limits the potential to compare healthy ageing across countries and/or populations. In this study, we developed a novel measurement scale of healthy ageing using worldwide cohorts. Methods: In the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) project, data from 16 international cohorts were harmonized. Using ATHLOS data, an item response theory (IRT) model was used to develop a scale with 41 items related to health and functioning. Measurement heterogeneity due to intra-dataset specificities was detected, applying differential item functioning via a logistic regression framework. The model accounted for specificities in model parameters by introducing cohort-specific parameters that rescaled scores to the main scale, using an equating procedure. Final scores were estimated for all individuals and converted to T-scores with a mean of 50 and a standard deviation of 10. Results: A common scale was created for 343 915 individuals above 18 years of age from 16 studies. The scale showed solid evidence of concurrent validity regarding various sociodemographic, life and health factors, and convergent validity with healthy life expectancy (r = 0.81) and gross domestic product (r = 0.58). Survival curves showed that the scale could also be predictive of mortality. Conclusions: The ATHLOS scale, due to its reliability and global representativeness, has the potential to contribute to worldwide research on healthy ageing

Erfarenheter av e-lärande i Sverige - en fallstudie

Vi presenterar en högskolekurs i "webbutveckling" som undervisats vid Malmö högskola som en distanskurs sedan 2002. Vi diskuterar kursmålen, undervisningsformer och studieresultat som funktion av webb-baserat kursmaterial och e-lärandeformen. Vi studerar positiva och negativa aspekter av "tillgänglighet". Många metoder och lösningar till uppgifter finns åtkomliga på webben. Hur påverkar detta lärandet och hur går man från kopiering som ett sätt att fuska till kopiering som ett sätt att lära sig? Genom åren har de externa parametrarna för kursen förändrats, t.ex. har kursen genomförts med tre olika LMS-system sedan starten. Med erfarenheterna från dessa presenterar vi en kort lista på funktionella krav vi tycker att ett LMS ska uppfylla för att fungera väl på distanskurser i högre utbildning.We present a university course in "Web Development" that has been taught at Malmö University since 2002 as a distance and e-learning course. We discuss course content, objectives and student results as a function of web-based course material and e-learning set-up. We study the positive and negative effects of "availability." Many of the solutions and methods taught in the course are available on the web. How does this affect learning and how does one move from copying as a way of cheaingt, to copying as a means of learning? Over time the outside parameters of the course have changed, e.g., the "Learning Management Systems" (LMS) have changed three times since the conception of the course. We present a short list of requirements for LMS-systems to be able to function well in e-learning courses in higher education

Erfarenheter av e-lärande i Sverige - en fallstudie

Vi presenterar en högskolekurs i "webbutveckling" som undervisats vid Malmö högskola som en distanskurs sedan 2002. Vi diskuterar kursmålen, undervisningsformer och studieresultat som funktion av webb-baserat kursmaterial och e-lärandeformen. Vi studerar positiva och negativa aspekter av "tillgänglighet". Många metoder och lösningar till uppgifter finns åtkomliga på webben. Hur påverkar detta lärandet och hur går man från kopiering som ett sätt att fuska till kopiering som ett sätt att lära sig? Genom åren har de externa parametrarna för kursen förändrats, t.ex. har kursen genomförts med tre olika LMS-system sedan starten. Med erfarenheterna från dessa presenterar vi en kort lista på funktionella krav vi tycker att ett LMS ska uppfylla för att fungera väl på distanskurser i högre utbildning.We present a university course in "Web Development" that has been taught at Malmö University since 2002 as a distance and e-learning course. We discuss course content, objectives and student results as a function of web-based course material and e-learning set-up. We study the positive and negative effects of "availability." Many of the solutions and methods taught in the course are available on the web. How does this affect learning and how does one move from copying as a way of cheaingt, to copying as a means of learning? Over time the outside parameters of the course have changed, e.g., the "Learning Management Systems" (LMS) have changed three times since the conception of the course. We present a short list of requirements for LMS-systems to be able to function well in e-learning courses in higher education

Analysis of the transcriptional control region of JC polyomavirus in cerebrospinal fluid from HIV-negative patients with progressive multifocal leucoencephalopathy.

The human polyomavirus JC (JCV) is the causative agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). JCV has a hyper-variable non-coding transcriptional control region (TCR), which contains the origin of replication and the promoters of viral transcription and replication. The archetype form of TCR-JCV is frequently found in the urine and kidneys of healthy and immunocompromised subjects. However, the rearranged forms, possibly generated by deletion and duplication of segments of the archetype sequence, are found in the peripheral blood, cerebrospinal fluid (CSF), and brain of PML patients. Most experience on this setting has come from the human immunodeficiency virus (HIV) pandemic. Little has been described on the JCV-TCR sequences from PML-HIV-negative patients affected by other immunosuppressive disorders. The aim of this study was to analyze the JCV-TCR detected in CSF samples from 12 HIV-negative immunosuppressed patients suffering from PML and to investigate the possible role of genomic organization in the different incidences of PML in HIV-positive and HIV-negative patients. The results confirm that the JCV-TCR rearrangements play a crucial role in the development of PML, although they do not account for the higher frequency of the disease in HIV infection. These data support the hypothesis that, independently of the rearrangement patterns of JCV-TCR, the direct action of HIV together with other as yet unidentified cellular determinants can be a key to explaining the high rate of PML in HIV infection with respect to other underlying immunosuppressive conditions

Etravirine concentrations in seminal plasma in HIV-infected patients

Purpose of the study: Good penetration of antiretroviral drugs to the seminal plasma may be associated with a decrease in viral replication and play an important role in the prevention of sexual transmission of HIV. We present data from a series of HIV-infected ARV-experienced patients receiving etravirine-containing regimens, in whom etravirine concentrations and viral loads were determined in blood plasma and seminal plasma. The objective was to determine etravirine concentrations and HIV-1 viral load (VL) in blood plasma (BP) and seminal plasma (SP) of HIV-infected patients. Methods: Ten HIV-1 adult antiretroviral-experienced patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Semen and blood samples were both collected around 12–24 h after the last etravirine dose, depending on once-daily or twice-daily dosing, respectively. HPLC/MS/MS was used to determine etravirine concentrations, and HIV-1 VL was determined by real-time PCR (limit of detection, VL 40 copies/mL). Results: Ten blood and twenty semen samples were collected. Median (range) CD4 count was 502 cells/mm3 (252–817) and median (range) BP VL was<40 copies/mL (40–362). Median (range) time on etravirine was 52 weeks (12–124). Median (range) BP etravirine concentration was 452.5 ng/mL (258–751). Median (range) SP etravirine concentration was 62.9 ng/mL (31.2–166), and values were above the protein-free IC50 range (0.39–2.4 ng/mL) in all cases. Median (range) etravirine SP:BP ratio was 0.16 (0.07–0.26). SP VL was<40 copies/mL in all patients, whereas BP VL was detectable in one patient with poor adherence to treatment. Conclusions: Total etravirine concentrations in male genital secretion are modest, reaching only 16% of the BP concentration, but nevertheless, more than 10 times above the wild type IC50 range