Clinical outcomes post transition to adult services in young adults with perinatally acquired HIV infection: mortality, retention in care, and viral suppression

OBJECTIVE: Adolescence is the only age group globally where HIV associated mortality is rising, with poorer outcomes at all stages of the care cascade compared to adults. We examined post-transition outcomes for young adults living with perinatal HIV (YAPaHIV). DESIGN: Retrospective cohort analysis. SETTING: A tertiary Youth Friendly Service (YFS) London, UK. PARTICIPANTS: 180 YAPaHIV registered between 01.01.06 and 31.12.17 contributed 921 person-years of follow up post-transition to adult services. INTERVENTION: YFS with multidisciplinary care and walk-in access. MAIN OUTCOME MEASURES: mortality, morbidity, retention in care, antiretroviral (ART) uptake and HIV-viral load (HIV-VL) suppression. Crude incidence rates (CIR) are reported per 1000 person-years. RESULTS: Of 180 youth registered; 4 (2.2%) died, 14 (7.8%) transferred care and 4 (2.2%) were lost to follow up. For the 158 retained in care the median age was 22.9 years (IQR 20.3-25.4), 56% were female, 85% Black African, with a median length of follow up in adult care of 5.5 years (IQR 2.9-7.3). 157 (99.4%) ever received an ART prescription, 127/157 (81%) with a latest HIV-VL < 200 copies RNA/ml, median CD4 count of 626 cells/ul (IQR 441-820). The all-cause mortality was 4.3/1000 person-years (95% CI 1.2 - 11.1), ten fold the aged-matched UK HIV-negative population (0.43/1000 person-years (95% CI 0.41 - 0.44). Post-transition, 17/180 (9.4%) developed a new AIDS diagnosis; CIR 18.5/1000 person-years (95% CI 10.8 - 29.6). CONCLUSION: Whilst this youth-friendly multi-disciplinary service achieved high engagement and coverage of suppressive ART, mortality remains markedly increased compared to the general UK population

Beyond advocacy: making space for conservation scientists in public debate

The topic of advocacy by scientists has been debated for decades, yet there is little agreement about whether scientists can or should be advocates. The fear of crossing a line into advocacy continues to hold many scientists back from contributing to public discourse, impoverishing public debate about important issues. We believe that progress in this debate is limited by a misconception about the relationship between scientific integrity and objectivity. We begin by unpacking this relationship and debunking three common misconceptions about advocacy by scientists: namely, that advocacy is harmful to scientific credibility, beyond the scope of science, and incompatible with science, which is value-free. We propose new ways of thinking about responsible advocacy by conservation scientists, drawing on practices from the health sciences, where researchers and professional bodies are empowered to act as health advocates.In so doing, we hope to open further space for conservation scientists to actively and legitimately engage in public debate about conservation issues

A randomised feasibility trial of an intervention to support sharing of HIV status for 18-25-year olds living with perinatally acquired HIV compared with standard care: HIV Empowering Adults' Decisions to Share-UK/Uganda Project (HEADS-UP)

Abstract: Background: Young adults with perinatally acquired HIV (PAH) face several challenges, including adhering to antiretroviral therapy (ART), managing the risk of onward HIV transmission and maintaining positive well-being. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges by facilitating emotional and practical support. Rates of HIV status sharing are, however, low in this population. There are no existing interventions focused on sharing one's HIV status for young adults living with PAH. The HEADS-UP study is designed to develop and test the feasibility of an intervention to help the sharing of HIV status for young adults with PAH. Methods: The study is a 30-month multi-site randomised feasibility study across both a high-income/low-HIV prevalence country (UK) and a low-income/high-HIV prevalence country (Uganda). Phase 1 (12 months) will involve developing the intervention using qualitative interviews with 20 young people living with PAH (ten in the UK-18 to 29 years; ten in Uganda-18 to 25 years), 20 of their social network (friends, family, sexual partners as defined by the young person; ten in the UK, ten in Uganda) and ten professionals with experience working with young adults with PAH (five in the UK, five in Uganda). Phase 2 (18 months) involves conducting a randomised feasibility parallel group trial of the intervention alongside current standard of care condition in each country (main study) with 18- to 25-year olds with PAH. A sample size of 94 participants per condition (intervention or standard of care; 188 participants in total: 47 in each condition in each country) with data at both the baseline and 6-month follow-up time points, across UK and Ugandan sites will be recruited. Participants in the intervention condition will also complete measures immediately post-intervention. Face-to-face interviews will be conducted with ten participants in both countries immediately post-intervention and at 6-month follow-up (sub-study). Discussion: This study will be the first trial that we are aware of to address important gaps in understanding acceptable and feasible ways of delivering HIV status sharing support for young people living with PAH. Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January, 2019. Study sponsor: Royal Holloway University of London. Sponsor contact: [email protected]. Date and version: April 2020. Protocol version 3.5

"The difference that makes a difference": highlighting the role of variable contexts within an HIV Prevention Community Randomised Trial (HPTN 071/PopART) in 21 study communities in Zambia and South Africa.

This paper explores contextual heterogeneity within a community randomised trial HPTN 071 (Population Effects of Antiretroviral Treatment to Reduce HIV Transmission) carried out in 21 study communities (12 Zambian, 9 South African). The trial evaluates the impact of a combination HIV prevention package (including household-based HIV counselling and testing and anti-retroviral treatment (ART) eligibility regardless of CD4-count) on HIV incidence. The selection, matching and randomisation of study communities relied on key epidemiological and demographic variables and community and stakeholder support. In 2013, following the selection of study communities, a "Broad Brush Survey" (BBS) approach was used to rapidly gather qualitative data on each study community, prior to the implementation of the trial intervention. First-year process indicator intervention data (2014-2015) were collected during the household-based intervention by community lay workers. Using an open/closed typology of urban communities (indicating more or less heterogeneity), this qualitative inquiry presents key features of 12 Zambian communities using a list of four meta-indicators (physical features, social organisation, networks and community narratives). These indicators are then compared with four intervention process indicators in a smaller set of four study communities. The process indicators selected for this analysis indicate response to the intervention (uptake) amongst adults. The BBS qualitative data are used to interpret patterns of similarity and variability in the process indicators across four communities. We found that meta-indicators of local context helped to interpret patterns of similarity and variability emerging across and within the four communities. Features especially significant for influencing heterogeneity in process indicators include proportion of middle-class residents, proximity to neighbouring communities and town centre, the scale of the informal economy, livelihood-linked mobility, presence of HIV stakeholders over time and commitment to community action. Future interdisciplinary analysis is needed to explore if these patterns of difference continue to hold up over the full intervention period and all intervention communities

Framing the private land conservation conversation: Strategic framing of the benefits of conservation participation could increase landholder engagement

How conservation messages are framed will likely impact on the success of our efforts to engage people in conservation action. This is highly relevant in the private land conservation (PLC) sector given the low participation rates of landholders. Using a case study of PLC schemes targeted at Australian landholders, we present the first systematic analysis of communication strategies used by organisations and government departments delivering those schemes to engage the public. We develop a novel approach for analysing the framing of conservation messages that codes the stated benefits of schemes according to value orientation. We categorised the benefits as flowing to either the landholder, to society, or to the environment, corresponding to the egoistic, altruistic and biospheric value orientations that have been shown to influence human behaviour. We find that messages are biased towards environmental benefits. Surprisingly, this is the case even for market-based schemes that have the explicit objective of appealing to production-focussed landholders and those who are not already involved in conservation. The risk is that PLC schemes framed in this way will fail to engage more egoistically oriented landholders and are only likely to appeal to those most likely to already be conservation-minded. By understanding the frame in which PLC benefits are communicated, we can begin to understand the types of people who may be engaged by these messages, and who may not be. Results suggest that the framing of the communications for many schemes could be broadened to appeal to a more diverse group (and thus ultimately to a larger group) of landholders

Chance mechanisms affecting the burden of metastases

BACKGROUND: The burden of cancer metastases within an individual is commonly used to clinically characterize a tumor's biological behavior. Assessments like these implicitly assume that spurious effects can be discounted. Here the influence of chance on the burden of metastasis is studied to determine whether or not this assumption is valid. METHODS: Monte Carlo simulations were performed to estimate tumor burdens sustained by individuals with cancer, based upon empirically derived and validated models for the number and size distributions of metastases. Factors related to the intrinsic metastatic potential of tumors and their host microenvironments were kept constant, to more clearly demonstrate the contribution from chance. RESULTS: Under otherwise identical conditions, both the simulated numbers and the sizes of metastases were highly variable. Comparable individuals could sustain anywhere from no metastases to scores of metastases, and the sizes of the metastases ranged from microscopic to macroscopic. Despite the marked variability in the number and sizes of the metastases, their respective growth times were rather more narrowly distributed. In such situations multiple occult metastases could develop into fully overt lesions within a comparatively short time period. CONCLUSION: Chance can have a major effect on the burden of metastases. Random variability can be so great as to make individual assessments of tumor biology unreliable, yet constrained enough to lead to the apparently simultaneous appearance of multiple overt metastases

Nanostructured Melt-Spun Sm(Co,Fe,Zr,B)7:5 Alloys for High-Temperature Magnets

High coercivity, the highest for Cu-free 2 : 17 Sm-Co ribbons, has been obtained in as-spun (= 211 kOe) and short time annealed (= 232 kOe) samples of Sm(CobalFe Zr B)7 5 alloys, with varying B, Zr, and Fe content (= 0-0 06, = 0-0 16, = 0 08-0 3) and wheel speed. In as-spun samples, the TbCu7 type structure and in annealed samples the Th2Zn17 and CaCu5 type structures is observed, plus fcc Co as minority phase is observed. Reduced remanence () is higher than 0.7. High-temperature magnetic measurements show very good stability above 300 C with coercive field as high as 5.2 kOe at 330 C. For annealed Sm(CobalFe0 3Zr0 02B0 04)7 5, very good loop squareness and high maximum energy product of 10.7 MGOe have been obtained. Increasing Zr content results in less uniform microstructure of annealed ribbons.Comment: IEEE Transactions on Magnetics, Vol. 39, No. 5, pages 2869 - 2871, September 200

Enhanced normalisation of CD4/CD8 ratio with earlier antiretroviral therapy at Primary HIV Infection.

BACKGROUND: Total CD4 T-cell counts predict HIV disease progression, but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite ART, recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals. METHODS: CD4 count and CD4/CD8 ratio were analyzed using data from two cohorts: SPARTAC trial, and the UK HIV Seroconverters Cohort where Primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD41.0). FINDINGS: Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression end point (aHR [95% CI] = 0.52 [0.32, 0.82], p=0.005). The longer the interval between seroconversion and ART initiation (HR [95% CI] =0.98 per month increase [0.97, 0.99], p<0.001) the less likely CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize (HR [95% CI] =2.47 [1.67, 3.67], p<0.001) than those initiating later. INTERPRETATION: The majority of individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner ART is initiated in PHI the greater the probability of achieving normal CD4/CD8 ratio

Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review

Introduction: Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilisation of ART for immediate treatment and prevention of HIV infection. Discussion: Missed acute HIV infection prevents people living with HIV (PLWH) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. Whilst immediate ART is recommended for all PLWH, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As roll-out of PrEP continues, HIV testing algorithms may need to be modified. Conclusions: With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance is needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable

Spinning plates: livelihood mobility, household responsibility and anti-retroviral treatment in an urban Zambian community during the HPTN 071 (PopART) study

INTRODUCTION: Qualitative data are lacking on the impact of mobility among people living with HIV (PLHIV) and their decision-making around anti-retroviral treatment (ART). We describe challenges of juggling household responsibility, livelihood mobility and HIV management for six PLHIV in urban Zambia. METHODS: Six PLHIV (three men and three women, aged 21 to 44) were recruited from different geographic zones in one urban community drawn from a qualitative cohort in a social science component of a cluster-randomized trial (HPTN071 PopART). Participants were on ART (n = 2), not on ART (n = 2) and had started and stopped ART (n = 2). At least two in-depth interviews and participant observations, and three drop-in household visits with each were carried out between February and August 2017. Themed and comparative analysis was conducted. RESULTS: The six participants relied on the informal economy to meet basic household needs. Routine livelihood mobility, either within the community and to a nearby town centre, or further afield for longer periods of time, was essential to get by. Although aware of ART benefits, only one of the six participants managed to successfully access and sustain treatment. The other five struggled to find time to access ART alongside other priorities, routine mobility and when daily routines were more chaotic. Difficulty in accessing ART was exacerbated by local health facility factors (congestion, a culture of reprimanding PLHIV who miss appointments, sporadic rationed drug supply), stigma and more limited social capital. CONCLUSIONS: Using a time-space framework illustrated how household responsibility, livelihood mobility and HIV management every day were like spinning plates, each liable to topple and demanding constant attention. If universal lifelong ART is to be delivered, the current service model needs to adjust the limited time that some PLHIV have to access ART because of household responsibilities and the need to earn a living moving around, often away from home. Practical strategies that could facilitate ART access in the context of livelihood mobility include challenging the practice of reprimand, improving drug supply, having ART services more widely distributed, mapped and available at night and weekends, and an effective centralized client health information system