Trends and predictors of linkage to HIV outpatient care following diagnosis in the era of expanded testing in England, Wales and Northern Ireland: Results of a national cohort study

OBJECTIVES: We explore trends in linkage to HIV care following diagnosis and investigate the impact of diagnosis setting on linkage in the era of expanded testing. METHODS: All adults (aged ≥ 15 years) diagnosed with HIV between 2005 and 2014 in England, Wales and Northern Ireland (EW&NI) were followed up until the end of 2017. People who died within 1 month of diagnosis were excluded (n = 1009). Trends in linkage to outpatient care (time to first CD4 count) were examined by sub-population and diagnosis setting. Logistic regression identified predictors of delayed linkage of > 1 month, > 3 months and > 1 year post-diagnosis (2012-2014). RESULTS: Overall, 97% (60 250/62 079) of people linked to care; linkage ≤ 1 month was 75% (44 291/59 312), ≤ 3 months was 88% (52 460) and ≤ 1 year was 95% (56 319). Median time to link declined from 15 days [interquartile range (IQR): 4-43] in 2005 to 6 (IQR: 0-20) days in 2014 (similar across sub-populations/diagnosis settings). In multivariable analysis, delayed linkage to care was associated with acquiring HIV through injecting drug use, heterosexual contact or other routes compared with sex between men (> 1 month/3 months/1 year), being diagnosed in earlier years (> 1 month/3 months/1 year) and having a first CD4 ≥ 200 cells/μL (> 3 months/1 year). Diagnosis outside of sexual health clinics, antenatal services and infectious disease units predicted delays of > 1 month. By 3 months, only diagnosis in 'other' settings (prisons, drug services, community and other medical settings) was significant. CONCLUSIONS: Linkage to care following HIV diagnosis is relatively timely in EW&NI. However, non-traditional testing venues should have well-defined referral pathways established to facilitate access to care and treatment

Community interventions to prevent violence against women and girls in informal settlements in Mumbai: the SNEHA-TARA pragmatic cluster randomised controlled trial

BACKGROUND In a cluster randomised controlled trial in Mumbai slums, we will test the effects on the prevalence of violence against women and girls of community mobilisation through groups and individual volunteers. One in three women in India has survived physical or sexual violence, making it a major public health burden. Reviews recommend community mobilisation to address violence, but trial evidence is limited. METHODS Guided by a theory of change, we will compare 24 areas receiving support services, community group, and volunteer activities with 24 areas receiving support services only. These community mobilisation activities will be evaluated through a follow-up survey after 3 years. Primary outcomes will be prevalence in the preceding year of physical or sexual domestic violence, and prevalence of emotional or economic domestic violence, control, or neglect against women 15–49 years old. Secondary outcomes will describe disclosure of violence to support services, community tolerance of violence against women and girls, prevalence of non-partner sexual violence, and mental health and wellbeing. Intermediate theory-based outcomes will include bystander intervention, identification of and support for survivors of violence, changes described in programme participants, and changes in communities. DISCUSSION Systematic reviews of interventions to prevent violence against women and girls suggest that community mobilisation is a promising population-based intervention. Already implemented in other areas, our intervention has been developed over 16 years of programmatic experience and 2 years of formative research. Backed by public engagement and advocacy, our vision is of a replicable community-led intervention to address the public health burden of violence against women and girls. TRIAL REGISTRATION Controlled Trials Registry of India, CTRI/2018/02/012047. Registered on 21 February 2018. ISRCTN, ISRCTN84502355. Registered on 22 February 2018

Sexual behaviours, HIV testing, and the proportion of men at risk of transmitting and acquiring HIV in London, UK, 2000-13: a serial cross-sectional study

BACKGROUND: HIV incidence in men who have sex with men (MSM) in the UK has remained unchanged over the past decade despite increases in HIV testing and antiretroviral therapy (ART) coverage. In this study, we examine trends in sexual behaviours and HIV testing in MSM and explore the risk of transmitting and acquiring HIV. METHODS: In this serial cross-sectional study, we obtained data from ten cross-sectional surveys done between 2000 and 2013, consisting of anonymous self-administered questionnaires and oral HIV antibody testing in MSM recruited in gay social venues in London, UK. Data were collected between October and January for all survey years up to 2008 and between February and August thereafter. All men older than 16 years were eligible to take part and fieldworkers attempted to approach all MSM in each venue and recorded refusal rates. Data were collected on demographic and sexual behavioural characteristics. We analysed trends over time using linear, logistic, and quantile regression. FINDINGS: Of 13 861 questionnaires collected between 2000 and 2013, we excluded 1985 (124 had completed the survey previously or were heterosexual reporting no anal intercourse in the past year, and 1861 did not provide samples for antibody testing). Of the 11 876 eligible MSM recruited, 1512 (13%) were HIV positive, with no significant trend in HIV positivity over time. 35% (531 of 1505) of HIV-positive MSM had undiagnosed infection, which decreased non-linearly over time from 34% (45 of 131) to 24% (25 of 106; p=0·01), while recent HIV testing (ie, in the past year) increased from 26% (263 of 997) to 60% (467 of 777; p<0·0001). The increase in recent testing in undiagnosed men (from 29% to 67%, p<0·0001) and HIV-negative men (from 26% to 62%, p<0·0001) suggests that undiagnosed infection might increasingly be recently acquired infection. The proportion of MSM reporting unprotected anal intercourse (UAI) in the past year increased from 43% (513 of 1187) to 53% (394 of 749; p<0·0001) and serosorting (exclusively) increased from 18% (207 of 1132) to 28% (177 of 6369; p<0·0001). 268 (2%) of 11 570 participants had undiagnosed HIV and reported UAI in the past year were at risk of transmitting HIV. Additionally 259 (2%) had diagnosed infection and reported UAI and non-exclusive serosorting in the past year. Although we did not collect data on antiretroviral therapy or viral load, surveillance data suggests that a small proportion of men with diagnosed infection will have detectable viral load and hence might also be at risk of transmitting HIV. 2633 (25%) of 10 364 participants were at high risk of acquiring HIV (defined as HIV-negative MSM either reporting one or more casual UAI partners in the past year or not exclusively serosorting). The proportions of MSM at risk of transmission or acquisition changed little over time (p=0·96 for MSM potentially at risk of transmission and p=0·275 for MSM at high risk of acquiring HIV). Undiagnosed men reporting UAI and diagnosed men not exclusively serosorting had consistently higher partner numbers than did other MSM over the period (median ranged from one to three across surveys in undiagnosed men reporting UAI, two to ten in diagnosed men not exclusively serosorting, and none to two in other men). INTERPRETATION: An increasing proportion of undiagnosed HIV infections in MSM in London might have been recently acquired, which is when people are likely to be most infectious. High UAI partner numbers of MSM at risk of transmitting HIV and the absence of a significant decrease in the proportion of men at high risk of acquiring the infection might explain the sustained HIV incidence. Implementation of combination prevention interventions comprising both behavioural and biological interventions to reduce community-wide risk is crucial to move towards eradication of HIV. FUNDING: Public Health England

Participatory women’s groups and counseling through home visits to improve child growth in rural eastern India: protocol for a cluster randomised controlled trial

Background: Childhood stunting (low height-for-age) is a marker of chronic undernutrition and predicts children’s subsequent physical and cognitive development. An estimated 52 million children in India are stunted. There is a broad consensus on determinants of child undernutrition and interventions to address it, but a lack of operational research testing strategies to increase the coverage of these interventions in high burden areas. Our study aims to assess the impact, costeffectiveness, and scalability of a community intervention involving a government-proposed community-based worker to improve growth in children under two

Where do we diagnose HIV infection? Monitoring new diagnoses made in nontraditional settings in England, Wales and Northern Ireland.

OBJECTIVES: The objectives of the study were to describe 10-year trends in HIV diagnosis setting and to explore predictors of being diagnosed outside a sexual health clinic (SHC). METHODS: Analyses of national HIV surveillance data were restricted to adults (aged ≥ 15 years) diagnosed in 2005-2014 in England, Wales and Northern Ireland. Logistic regression identified factors associated with diagnosis outside an SHC (2011-2014). RESULTS: Between 2005 and 2014, 63 599 adults were newly diagnosed with HIV infection; 83% had a diagnosis setting reported. Most people were diagnosed in SHCs (69%) followed by: medical admissions/accident and emergency (A&E; 8.6%), general practice (6.4%), antenatal services (5.5%), out-patient services (3.6%), infectious disease units (2.7%) and other settings (4.0%). The proportion of people diagnosed outside SHCs increased from 2005 to 2014, overall (from 27% to 32%, respectively) and among men who have sex with men (MSM) (from 14% to 21%) and black African men (from 25% to 37%) and women (from 39% to 52%) (all trend P < 0.001). Median CD4 increased across all settings, but was highest in SHCs (384 cells/μL) and lowest in medical admissions/A&E (94 cells/μL). Predictors of being diagnosed outside SHCs included: acquiring HIV through heterosexual contact [adjusted odds ratio (aOR) 1.99; 95% confidence interval (CI) 1.81-2.18] or injecting drug use (aOR: 3.28; 95% CI: 2.56-4.19; reference: MSM), being diagnosed late (< 350 cells/μL) (aOR: 2.55; 95% CI: 2.36-2.74; reference: diagnosed promptly) and being of older age at diagnosis (35-49 years: aOR: 1.60; 95% CI: 1.39-1.83; ≥ 50 years: aOR: 2.48; 95% CI: 2.13-2.88; reference: 15-24 years). CONCLUSIONS: The proportion of HIV diagnoses made outside SHCs has increased over the past decade in line with evolving HIV testing guidelines. However, the rate of late diagnosis remains high, indicating that further expansion of testing is necessary, as many people may have had missed opportunities for earlier diagnosis

Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort

BACKGROUND: Deaths in HIV-positive people have decreased since the introduction of highly active antiretroviral therapy (HAART) in 1996. Fewer AIDS-related deaths and an ageing cohort have resulted in an increase in the proportion of HIV patients dying from non-AIDS-related disorders. Here we describe mortality and causes of death in people diagnosed with HIV in the HAART era compared with the general population. METHODS: In this observational analysis, we linked cohort data collected by Public Health England (PHE) for individuals aged 15 years and older, diagnosed with HIV in England and Wales from 1997 to 2012, to the Office for National Statistics (ONS) national mortality register. Cohort inclusion began at diagnosis with follow-up clinical information collected every year from all 220 National Health Service (NHS) HIV outpatient clinics nationwide. To classify causes of death we used a modified Coding Causes of Death in HIV (CoDe) protocol, which uses death certificate data and clinical markers. We applied Kaplan-Meier analysis for survival curves and mortality rate estimation and Cox regression to establish independent predictors of all-cause mortality, adjusting for sex, infection route, age at diagnosis, region of birth, year of diagnosis, late diagnosis, and history of HAART. We used standardised mortality ratios (SMRs) to make comparisons with the general population. FINDINGS: Between 1997 and 2012, 88 994 people were diagnosed with HIV, contributing 448 839 person-years of follow up. By the end of 2012, 5302 (6%) patients had died (all-cause mortality 118 per 10 000 person-years, 95% CI 115–121). In multivariable analysis, late diagnosis was a strong predictor of death (hazard ratio [HR] 3·50, 95% CI 3·13–3·92). People diagnosed more recently had a lower risk of death (2003–07: HR 0·66, 95% CI 0·62–0·70; 2008–12: HR 0·65, 95% CI 0·60–0·71). Cause of death was determinable for 4808 (91%) of 5302 patients; most deaths (2791 [58%] of 4808) were attributable to AIDS-defining illnesses. Cohort mortality was significantly higher than the general population for all causes (SMR 5·7, 95% CI 5·5–5·8), particularly non-AIDS infections (10·8, 9·8–12·0) and liver disease (3·7, 3·3–4·2). All-cause mortality was highest in the year after diagnosis (SMR 24·3, 95% CI 23·4–25·2). INTERPRETATION: Despite the availability of free treatment and care in the UK, AIDS continues to account for the majority of deaths in HIV-positive people, and mortality remains higher in HIV-positive people than in the general population. These findings highlight the importance of prompt diagnosis, care engagement, and optimum management of comorbidities in reducing mortality in people with HIV

Overstating the evidence - double counting in meta-analysis and related problems

Background: The problem of missing studies in meta-analysis has received much attention. Less attention has been paid to the more serious problem of double counting of evidence. Methods: Various problems in overstating the precision of results from meta-analyses are described and illustrated with examples, including papers from leading medical journals. These problems include, but are not limited to, simple double-counting of the same studies, double counting of some aspects of the studies, inappropriate imputation of results, and assigning spurious precision to individual studies. Results: Some suggestions are made as to how the quality and reliability of meta-analysis can be improved. It is proposed that the key to quality in meta-analysis lies in the results being transparent and checkable. Conclusions: Existing quality check lists for meta-analysis do little to encourage an appropriate attitude to combining evidence and to statistical analysis. Journals and other relevant organisations should encourage authors to make data available and make methods explicit. They should also act promptly to withdraw meta-analyses when mistakes are found

Effectiveness of participatory women’s groups scaled up by the public health system to improve birth outcomes in Jharkhand, eastern India: a pragmatic cluster non-randomised controlled trial

INTRODUCTION: The WHO recommends community mobilisation with women’s groups practising participatory learning and action (PLA) to improve neonatal survival in high-mortality settings. This intervention has not been evaluated at scale with government frontline workers. METHODS: We did a pragmatic cluster non-randomised controlled trial of women’s groups practising PLA scaled up by government front-line workers in Jharkhand, eastern India. Groups prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies and evaluated progress. Intervention coverage and quality were tracked state-wide. Births and deaths to women of reproductive age were monitored in six of Jharkhand’s 24 districts: three purposively allocated to an early intervention start (2017) and three to a delayed start (2019). We monitored vital events prospectively in 100 purposively selected units of 10 000 population each, during baseline (1 March 2017–31 August 2017) and evaluation periods (1 September 2017–31 August 2019). The primary outcome was neonatal mortality. RESULTS: We identified 51 949 deliveries and conducted interviews for 48 589 (93.5%). At baseline, neonatal mortality rates (NMR) were 36.9 per 1000 livebirths in the early arm and 39.2 in the delayed arm. Over 24 months of intervention, the NMR was 29.1 in the early arm and 39.2 in the delayed arm, corresponding to a 24% reduction in neonatal mortality (adjusted OR (AOR) 0.76, 95% CI 0.59 to 0.98), including 26% among the most deprived (AOR 0.74, 95% CI 0.57 to 0.95). Twenty of Jharkhand’s 24 districts achieved adequate meeting coverage and quality. In these 20 districts, the intervention saved an estimated 11 803 newborn lives (min: 1026–max: 20 527) over 42 months, and cost 41 international dollars per life year saved. CONCLUSION: Participatory women’s groups scaled up by the Indian public health system reduced neonatal mortality equitably in a largely rural state and were highly cost-effective, warranting scale-up in other high-mortality rural settings. TRIAL REGISTRATION: ISRCTN99422435