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Finding a cure for HIV: will it ever be achievable?
In: Journal of the International AIDS Society, Band 14, Heft 1, S. 4-4
ISSN: 1758-2652
Combination antiretroviral therapy (cART) has led to a major reduction in HIV‐related mortality and morbidity. However, HIV still cannot be cured. With the absence of an effective prophylactic or therapeutic vaccine, increasing numbers of infected people, emerging new toxicities secondary to cART and the need for life‐long treatment, there is now a real urgency to find a cure for HIV.There are currently multiple barriers to curing HIV. The most significant barrier is the establishment of a latent or "silent" infection in resting CD4+ T cells. In latent HIV infection, the virus is able to integrate into the host cell genome, but does not proceed to active replication. As a consequence, antiviral agents, as well as the immune system, are unable to eliminate these long‐lived, latently infected cells. Reactivation of latently infected resting CD4+ T cells can then re‐establish infection once cART is stopped. Other significant barriers to cure include residual viral replication in patients receiving cART, even when the virus is not detectable by conventional assays. In addition, HIV can be sequestered in anatomical reservoirs, such as the brain, gastrointestinal tract and genitourinary tract.Achieving either a functional cure (long‐term control of HIV in the absence of cART) or a sterilizing cure (elimination of all HIV‐infected cells) remains a major challenge. Several studies have now demonstrated that treatment intensification appears to have little impact on latent reservoirs. Some potential and promising approaches that may reduce the latent reservoir include very early initiation of cART and the use of agents that could potentially reverse latent infection.Agents that reverse latent infection will promote viral production; however, simultaneous administration of cART will prevent subsequent rounds of viral replication. Such drugs as histone deacetylase inhibitors, currently used and licensed for the treatment of some cancers, or activating latently infected resting cells with cytokines, such as IL‐7 or prostratin, show promising results in reversing latency in vitro when used either alone or in combination. In order to move forward toward clinical trials that target eradication, there needs to be careful consideration of the risks and benefits of these approaches, agreement on the most informative endpoints for eradication studies and greater engagement of the infected community.
Contemporary Change in Traditional Societies. 2, Asian Rural Societies
In: Man: the journal of the Royal Anthropological Institute of Great Britain and Ireland, Band 3, Heft 2, S. 342
Viral suppression after 12 months of antiretroviral therapy in low- and middle-income countries: a systematic review
In: Bulletin of the World Health Organization: the international journal of public health = Bulletin de l'Organisation Mondiale de la Santé, Band 91, Heft 5, S. 377-385E
ISSN: 1564-0604
Contemporary Change in Traditional Societies. 2, Mexican and Peruvian Communities
In: Man: the journal of the Royal Anthropological Institute of Great Britain and Ireland, Band 3, Heft 4, S. 682
Job Placement and Follow-Up of Moderately and Severely Handicapped Individuals after Three Years
In: Research and Practice for Persons with Severe Disabilities, Band 7, Heft 2, S. 5-16
ISSN: 2169-2408
A Collaborative Rapid Persona-Building Workshop: Creating Design Personas with Health Researchers
In: International journal of sociotechnology and knowledge development: IJSKD ; an official publication of the Information Resources Management Association, Band 6, Heft 2, S. 17-35
ISSN: 1941-6261
In the HealthMap project for People With HIV, (PWHIV) designers employed a collaborative rapid 'persona-building' workshop with health researchers to develop patient personas that embodied patient-centred design goals and contextual awareness from a variety of qualitative and quantitative data. On reflection, this collaborative rapid workshop was a process for drawing together the divergent user research insights and expertise of stakeholders into focus for a chronic disease self-management design. This paper discusses, (i) an analysis of the transcript of the workshop and, (ii) interviews with five practising senior designers, in order to reflect on how the persona-building process was enacted and its role in the HealthMap design evolution. The collaborative rapid persona-building methodology supported: embedding user research insights, eliciting domain expertise, introducing design thinking, facilitating stakeholder collaboration and defining early design requirements. The contribution of this paper is to model the process of collaborative rapid persona-building and to introduce the collaborative rapid persona-building framework as a method to generate design priorities from domain expertise and user research data.
The HIV care cascade: a systematic review of data sources, methodology and comparability
In: Journal of the International AIDS Society, Band 18, Heft 1
ISSN: 1758-2652
IntroductionThe cascade of HIV diagnosis, care and treatment (HIV care cascade) is increasingly used to direct and evaluate interventions to increase population antiretroviral therapy (ART) coverage, a key component of treatment as prevention. The ability to compare cascades over time, sub‐population, jurisdiction or country is important. However, differences in data sources and methodology used to construct the HIV care cascade might limit its comparability and ultimately its utility. Our aim was to review systematically the different methods used to estimate and report the HIV care cascade and their comparability.MethodsA search of published and unpublished literature through March 2015 was conducted. Cascades that reported the continuum of care from diagnosis to virological suppression in a demographically definable population were included. Data sources and methods of measurement or estimation were extracted. We defined the most comparable cascade elements as those that directly measured diagnosis or care from a population‐based data set.Results and discussionsThirteen reports were included after screening 1631 records. The undiagnosed HIV‐infected population was reported in seven cascades, each of which used different data sets and methods and could not be considered to be comparable. All 13 used mandatory HIV diagnosis notification systems to measure the diagnosed population. Population‐based data sets, derived from clinical data or mandatory reporting of CD4 cell counts and viral load tests from all individuals, were used in 6 of 12 cascades reporting linkage, 6 of 13 reporting retention, 3 of 11 reporting ART and 6 of 13 cascades reporting virological suppression. Cascades with access to population‐based data sets were able to directly measure cascade elements and are therefore comparable over time, place and sub‐population. Other data sources and methods are less comparable.ConclusionsTo ensure comparability, countries wishing to accurately measure the cascade should utilize complete population‐based data sets from clinical data from elements of a centralized healthcare setting, where available, or mandatory CD4 cell count and viral load test result reporting. Additionally, virological suppression should be presented both as percentage of diagnosed and percentage of estimated total HIV‐infected population, until methods to calculate the latter have been standardized.
Routine versus Targeted Viral Load Strategy among Patients Starting Antiretroviral in Hanoi, Vietnam
In: Journal of the International AIDS Society, Band 22, Heft 3
ISSN: 1758-2652
AbstractIntroductionHIV viral load (VL) testing is recommended by the WHO as the preferred method for monitoring patients on antiretroviral therapy (ART). However, evidence that routine VL (RVL) monitoring improves clinical outcomes is lacking.MethodsWe conducted a prospective, randomized controlled trial of RVL monitoring every six months versus a targeted VL (TVL) strategy (routine CD4 plus VL testing if clinical or immunological failure) in patients starting ART between April 2011 and April 2014 at Bach Mai Hospital in Hanoi. Six hundred and forty‐seven subjects were randomized to RVL (n = 305) or TVL monitoring (n = 342) and followed up for three years. Primary endpoints were death or WHO clinical Stage 4 events between six and thirty‐six months of ART and rate of virological suppression at three years.ResultsOverall, 37.1% of subjects were female, median age was 33.4 years (IQR: 29.5 to 38.6), and 47% had a CD4 count ≤100 cells/mm3 at time of ART initiation. Approximately 44% of study events (death, LTFU, withdrawal, or Stage 4 event) and 68% of deaths occurred within the first six months of ART. Among patients on ART at six months, death or Stage 4 event occurred in 3.6% of RVL and 3.9% of TVL (p = 0.823). Survival analysis showed no significant difference between the groups (p = 0.825). Viral suppression at 36 months of ART was 97.2% in RVL and 98.9% in TVL (p = 0.206) at a threshold of 400 copies/mL and was 98.0% in RVL and 98.9% in TVL (p = 0.488) at 1000 copies/mL. In ITT analysis, 20.7% in RVL and 21.9% in TVL (p = 0.693) were unsuppressed at 1000 copies/mL.ConclusionsWe found no significant difference in rates of death or Stage 4 events and virological failure in patients with RVL monitoring compared to those monitored with a TVL strategy after three years of follow‐up. Viral suppression rates were high overall and there were few study events among patients alive and on ART after six months, limiting the study's power to detect a difference among study arms. Nonetheless, these data suggest that the choice of VL monitoring strategy may have less impact on patient outcomes compared to efforts to reduce early mortality and improve ART retention.
International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019
ABSTRACT Objective: There are over 4000 trials conducted in people with COVID-19. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for COVID-19 trials. Design: In an online survey conducted in English, Chinese, Italian, Portuguese and Spanish languages, adults with COVID-19, their family members, health professionals and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analysed thematically. Setting: International Participants: Adults aged 18 years and over with confirmed or suspected COVID-19, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). Main Results: In total, 9289 participants from 111 countries (776 people with COVID-19 or family members, 4882 health professionals, and 3631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean >7.5, median ≥ 8, and >70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals. ; The project is funded by the Flinders University and the National COVID-19 Clinical Evidence Taskforce, convened by the Australian Living Evidence Consortium, hosted by Cochrane Australia, School of Public Health and Preventive Medicine, Monash University supported by the Australian Government, Victorian Department of Health and Human Services, Ian Potter Foundation, Walter Cottman Endowment Fund (managed by Equity Trustees) and the Lord Mayor's Charitable Foundation). AT is supported by The University of Sydney Robinson Fellowship. ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z)
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Elective surgery cancellations due to the COVID-19 pandemic. Global predictive modelling to inform surgical recovery plans
Background: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. Methods: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. Results: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. Conclusion: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.
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