Feasibility of antiretroviral treatment monitoring in the era of decentralized HIV care: a systematic review

Background: Regular monitoring of HIV patients who are receiving antiretroviral therapy (ART) is required to ensure patient benefits and the long-term effectiveness and sustainability of ART programs. Prompted by WHO recommendations for expansion and decentralization of HIV treatment and care in low and middle income countries, we conducted a systematic review to assess the feasibility of treatment monitoring in these settings. Methods: A comprehensive search strategy was developed using a combination of MeSH and free text terms relevant to HIV treatment and care, health service delivery, health service accessibility, decentralization and other relevant terms. Five electronic databases and two conference websites were searched to identify relevant studies conducted in LMICs, published in English between Jan 2006 and Dec 2015. Outcomes of interest included the proportion of patients who received treatment monitoring and health system factors related to monitoring of patients on ART under decentralized HIV service delivery models. Results: From 5363 records retrieved, twenty studies were included in the review; all but one was conducted in subSaharan African countries. The majority of studies (15/20) had relatively short follow-up duration (≤24 months), and only two studies were specifically designed to assess treatment monitoring practices. The most frequently studied follow-up period was 12 months and a wide range of treatment monitoring coverage was observed. The reported proportions of patients on ART who received CD4 monitoring ranged from very low (6%; N = 2145) to very high (95%; N = 488). The median uptake of viral load monitoring was 86% with studies in program settings reporting coverage as low as 14%. Overall, the longer the follow-up period, the lower the proportion of patients who received regular monitoring tests; and programs in rural areas reported low coverage of laboratory monitoring. Moreover, uptake in the context of research had significantly better where monitoring was done by dedicated research staff. In the absence of point of care (POC) testing, the limited capacity for blood sample transportation between clinic and laboratory and poor quality of nursing staff were identified as a major barrier for treatment monitoring practice. Conclusions: There is a paucity of data on the uptake of treatment monitoring, particularly with longer-term followup. Wide variation in access to both virological and immunological regular monitoring was observed, with some clinics in well-resourced settings supported by external donors achieving high coverage. The feasibility of treatment monitoring, particularly in decentralized settings of HIV treatment and care may thus be of concern and requires further study. Significant investment in POC diagnostic technologies and, improving the quality of and training for nursing staff is required to ensure effective scale up of ART programs towards the targets of 90-90-90 by the year 2020

Assurance Requirements Compliance for the Greater Confinement Disposal Boreholes, Area 5 Radioactive Waste Management Site, Nevada Test Site

This paper addresses deficiencies identified with the. Performance Assessment for Greater Confinement Disposal (GCD) Boreholes compliance with the Title 40 Code of federal Regulations (CFR) Part 191.14, "Assurance Requirements" (CFR, 1985). The Transuransic Waste Disposal Federal Review Group (TFRG). and U.S Department of Energy Headquarters , need to concur that the assurance requirements have been met at the time of closure of the Area 5 Radioactive Waste Management Site

Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo

In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection

Complete genome sequence of the extremely acidophilic methanotroph isolate V4, Methylacidiphilum infernorum, a representative of the bacterial phylum Verrucomicrobia

<p>Abstract</p> <p>Background</p> <p>The phylum <it>Verrucomicrobia </it>is a widespread but poorly characterized bacterial clade. Although cultivation-independent approaches detect representatives of this phylum in a wide range of environments, including soils, seawater, hot springs and human gastrointestinal tract, only few have been isolated in pure culture. We have recently reported cultivation and initial characterization of an extremely acidophilic methanotrophic member of the <it>Verrucomicrobia</it>, strain V4, isolated from the Hell's Gate geothermal area in New Zealand. Similar organisms were independently isolated from geothermal systems in Italy and Russia.</p> <p>Results</p> <p>We report the complete genome sequence of strain V4, the first one from a representative of the <it>Verrucomicrobia</it>. Isolate V4, initially named "<it>Methylokorus infernorum</it>" (and recently renamed <it>Methylacidiphilum infernorum</it>) is an autotrophic bacterium with a streamlined genome of ~2.3 Mbp that encodes simple signal transduction pathways and has a limited potential for regulation of gene expression. Central metabolism of <it>M. infernorum </it>was reconstructed almost completely and revealed highly interconnected pathways of autotrophic central metabolism and modifications of C₁-utilization pathways compared to other known methylotrophs. The <it>M. infernorum </it>genome does not encode tubulin, which was previously discovered in bacteria of the genus <it>Prosthecobacter</it>, or close homologs of any other signature eukaryotic proteins. Phylogenetic analysis of ribosomal proteins and RNA polymerase subunits unequivocally supports grouping <it>Planctomycetes</it>, <it>Verrucomicrobia </it>and <it>Chlamydiae </it>into a single clade, the PVC superphylum, despite dramatically different gene content in members of these three groups. Comparative-genomic analysis suggests that evolution of the <it>M. infernorum </it>lineage involved extensive horizontal gene exchange with a variety of bacteria. The genome of <it>M. infernorum </it>shows apparent adaptations for existence under extremely acidic conditions including a major upward shift in the isoelectric points of proteins.</p> <p>Conclusion</p> <p>The results of genome analysis of <it>M. infernorum </it>support the monophyly of the PVC superphylum. <it>M. infernorum </it>possesses a streamlined genome but seems to have acquired numerous genes including those for enzymes of methylotrophic pathways <it>via </it>horizontal gene transfer, in particular, from <it>Proteobacteria</it>.</p> <p>Reviewers</p> <p>This article was reviewed by John A. Fuerst, Ludmila Chistoserdova, and Radhey S. Gupta.</p

Ages of onset of DSM-III anxiety disorders

The Diagnostic and Statistical Manual (DSM-III) contains little specific information pertaining to the ages of onset of anxiety disorders. Such information is of clinical and research value in understanding the natural history of mental illnesses, in determining which of several possible etiologies for a given diagnosis may be relevant for a particular patient, and in testing theories of psychopathology or pathophysiology. Age-of-onset data is presented for 423 psychiatric outpatients seen at a University Hospital--based anxiety disorders program. All adult anxiety disorders are represented except posttraumatic stress disorder. The relevance of this information is discussed in terms of past research on ages of onset of the anxiety disorders, and in its bearing on the psychiatric diagnosis of these conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25743/1/0000303.pd

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

A journey without maps—Understanding the costs of caring for dependent older people in Nigeria, China, Mexico and Peru

Purpose of the study: Populations in Latin America, Asia and sub-Saharan Africa are rapidly ageing. The extent to which traditional systems of family support and security can manage the care of increased numbers of older people with chronic health problems is unclear. Our aim was to explore the social and economic effects of caring for an older dependent person, including insight into pathways to economic vulnerability. Design & methods: We carried out a series of household case studies across urban and rural sites in Peru, Mexico, China and Nigeria (n = 24), as part of a cross-sectional study, nested within the 10/66 Dementia Research Group cohort. Case studies consisted of in-depth narrative style interviews (n = 60) with multiple family members, including the older dependent person. Results: Governments were largely uninvolved in the care and support of older dependent people, leaving families to negotiate a ‘journey without maps’. Women were de facto caregivers but the traditional role of female relative as caregiver was beginning to be contested. Household composition was flexible and responsive to changing needs of multiple generations but family finances were stretched. Implications: Governments are lagging behind sociodemographic and social change. There is an urgent need for policy frameworks to support and supplement inputs from families. These should include community-based and residential care services, disability benefits and carers allowances. Further enhancement of health insurance schemes and scale-up of social pensions are an important component of bolstering the security of dependent older people and supporting their continued social and economic participation

Systems serology detects functionally distinct coronavirus antibody features in children and elderly

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals