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Summary Background A target to eliminate HIV transmission in England by 2030 was set in early 2019. This study aimed to estimate trends from 2013 to 2019 in HIV prevalence, particularly the number of people living with undiagnosed HIV, by exposure group, ethnicity, gender, age group, and region. These estimates are essential to monitor progress towards elimination. Methods A Bayesian synthesis of evidence from multiple surveillance, demographic, and survey datasets relevant to HIV in England was used to estimate trends in the number of people living with HIV, the proportion of people unaware of their HIV infection, and the corresponding prevalence of undiagnosed HIV. All estimates were stratified by exposure group, ethnicity, gender, age group (15–34, 35–44, 45–59, or 60–74 years), region (London, or outside of London) and year (2013–19). Findings The total number of people living with HIV aged 15–74 years in England increased from 83 500 (95% credible interval 80 200–89 600) in 2013 to 92 800 (91 000–95 600) in 2019. The proportion diagnosed steadily increased from 86% (80–90%) to 94% (91–95%) during the same time period, corresponding to a halving in the number of undiagnosed infections from 11 600 (8300–17 700) to 5900 (4400–8700) and in undiagnosed prevalence from 0·29 (0·21–0·44) to 0·14 (0·11–0·21) per 1000 population. Similar steep declines were estimated in all subgroups of gay, bisexual, and other men who have sex with men and in most subgroups of Black African heterosexuals. The pace of reduction was less pronounced for heterosexuals in other ethnic groups and people who inject drugs, particularly outside London; however, undiagnosed prevalence in these groups has remained very low. Interpretation The UNAIDS target of diagnosing 90% of people living with HIV by 2020 was reached by 2016 in England, with the country on track to achieve the new target of 95% diagnosed by 2025. Reductions in transmission and undiagnosed prevalence have corresponded to large scale-up of testing in key populations and early diagnosis and treatment. Additional and intensified prevention measures are required to eliminate transmission of HIV among the communities that have experienced slower declines than other subgroups, despite having very low prevalences of HIV. Funding UK Medical Research Council and Public Health England.

Summary Background To manage the HIV epidemic among men who have sex with men (MSM) in England, treatment as prevention strategies based on test and treat were strengthened between 2011 and 2015, and supplemented from 2015 by scale-up of pre-exposure prophylaxis (PrEP). We examined the effect of these interventions on HIV incidence and investigated whether internationally agreed targets for HIV control and elimination of HIV transmission by 2030 might be within reach among MSM in England. Methods We used a novel, age-stratified, CD4-staged Bayesian back-calculation model to estimate HIV incidence and undiagnosed infections among adult MSM (age ≥15 years) during the 10-year period between 2009 and 2018. The model used data on HIV and AIDS diagnoses routinely collected via the national HIV and AIDS Reporting System in England, and knowledge on the progression of HIV through CD4-defined disease stages. Estimated incidence trends were extrapolated, assuming a constant MSM population from 2018 onwards, to quantify the likelihood of achieving elimination of HIV transmission, defined as less than one newly aquired infection per 10 000 MSM per year, by 2030. Findings The peak in HIV incidence in MSM in England was estimated with 80% certainty to have occurred in 2012 or 2013, at least 1 year before the observed peak in new diagnoses in 2014. Results indicated a steep decrease in the annual number of new infections among MSM, from 2770 (95% credible interval 2490–3040) in 2013 to 1740 (1500–2010) in 2015, followed by a steadier decrease from 2016, down to 854 (441–1540) infections in 2018. A decline in new infections was consistently estimated in all age groups, and was particularly marked in MSM aged 25–34 years, and slowest in those aged 45 years or older. Similar trends were estimated in the number of undiagnosed infections, with the greatest decrease after 2013 in the 25–34 years age group. Under extrapolation assumptions, we calculated a 40% probability of achieving the defined target elimination threshold by 2030. Interpretation The sharp decrease in HIV incidence, estimated to have begun before the scale up of PrEP, indicates the success of strengthening treatment as prevention measures among MSM in England. To achieve the 2030 elimination threshold, targeted policies might be required to reach those aged 45 years or older, in whom incidence is decreasing at the slowest rate. Funding UK Medical Research Council, UK National Institute of Health Research Health Protection Unit in Behavioural Science and Evaluation, and Public Health England.

Objectives We describe COVID‐19 mortality among people with and without HIV during the first wave of the pandemic in England. Methods National surveillance data on adults (aged ≥ 15 years) with diagnosed HIV resident in England were linked to national COVID‐19 mortality surveillance data (2 March 2020–16 June 2020); HIV clinicians verified linked cases and provided information on the circumstances of death. We present COVID‐19 mortality rates by HIV status, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity. Results Overall, 99 people with HIV, including 61 of black ethnicity, died of/with COVID‐19 (107/100 000) compared with 49 483 people without HIV (109/100 000). Compared to people without HIV, higher COVID‐19 mortality rates were observed in people with HIV of black (188 vs. 122/100 000) and Asian (131 vs. 77.0/100 000) ethnicity, and in both younger (15–59 years: 58.3 vs. 10.2/100 000) and older (≥ 60 years: 434 vs. 355/100 000) people. After adjustment for demographic factors, people with HIV had a higher COVID‐19 mortality risk than those without (2.18; 95% CI: 1.76–2.70). Most people with HIV who died of/with COVID‐19 had suppressed HIV viraemia (91%) and at least one comorbidity reported to be associated with poor COVID‐19 outcomes (87%). Conclusions In the first wave of the pandemic in England, COVID‐19 mortality among people with HIV was low, but was higher than in those without HIV, after controlling for demographic factors. This supports the strategy of prioritizing COVID‐19 vaccination for people with HIV and strongly encouraging its uptake, especially in those of black and Asian ethnicity.

Background The assumption that migrants acquire human immunodeficiency virus (HIV) before migration, particularly those from high prevalence areas, is common. Aim We assessed the place of HIV acquisition of migrants diagnosed in four European countries using surveillance data. Methods Using CD4+ T-cell count trajectories modelled to account for seroconversion bias, we estimated infection year of newly HIV-diagnosed migrants residing in the United Kingdom (UK), Belgium, Sweden and Italy with a known arrival year and CD4+ T-cell count at diagnosis. Multivariate analyses identified predictors for post-migration acquisition. Results Between 2007 and 2016, migrants constituted 56% of people newly diagnosed with HIV in the UK, 62% in Belgium, 72% in Sweden and 29% in Italy. Of 23,595 migrants included, 60% were born in Africa and 70% acquired HIV heterosexually. An estimated 9,400 migrants (40%; interquartile range (IQR): 34–59) probably acquired HIV post-migration. This proportion was similar by risk group, sex and region of birth. Time since migration was a strong predictor of post-migration HIV acquisition: 91% (IQR: 87–95) among those arriving 10 or more years prior to diagnosis; 30% (IQR: 21–37) among those 1–5 years prior. Younger age at arrival was a predictor: 15–18 years (81%; IQR: 74–86), 19–25 years (53%; IQR: 45–63), 26–35 years (37%; IQR: 30–46) and 36 years and older (25%; IQR: 21–33). Conclusions Migrants, regardless of origin, sex and exposure to HIV are at risk of acquiring HIV post-migration to Europe. Alongside accessible HIV testing, prevention activities must target migrant communities.

BACKGROUND:Near 60% of new HIV infections in the United Kingdom are estimated to occur in men who have sex with men (MSM). Age-disassortative partnerships in MSM have been suggested to spread the HIV epidemics in many Western developed countries and to contribute to ethnic disparities in infection rates. Understanding these mixing patterns in transmission can help to determine which groups are at a greater risk and guide public health interventions. METHODS:We analyzed combined epidemiologic data and viral sequences from MSM diagnosed with HIV at the national level. We applied a phylodynamic source attribution model to infer patterns of transmission between groups of patients. RESULTS:From pair probabilities of transmission between 14 603 MSM patients, we found that potential transmitters of HIV subtype B were on average 8 months older than recipients. We also found a moderate overall assortativity of transmission by ethnic group and a stronger assortativity by region. CONCLUSIONS:Our findings suggest that there is only a modest net flow of transmissions from older to young MSM in subtype B epidemics and that young MSM, both for Black or White groups, are more likely to be infected by one another than expected in a sexual network with random mixing.

ObjectiveA resurgence in bacterial STIs, notably syphilis, among gay, bisexual and other men who have sex with men (MSM) has been detected in England. A Canadian modelling study postulated that antiretroviral therapy (ART) may increase susceptibility to syphilis. We assess the association between ART and syphilis incidence in a comprehensive national cohort of MSM living with HIV in England.MethodsNational surveillance data were used to create a cohort of MSM attending for both HIV and STI care in England between 2009 and 2016. Survival analysis was used to calculate the incidence of infectious syphilis during periods on and off ART. Multivariable Poisson regression was used to assess the association between ART use and syphilis, after adjustment for potential confounders, including, as a proxy measure for high-risk behaviour, being diagnosed with >1 other STI prior to a syphilis diagnosis.Results19 428 HIV diagnosed MSM contributed 112 960 person-years of follow-up from 2009 to 2016. The overall rate of syphilis was 78.0 cases per 1000 person-years follow-up. Syphilis rates were higher among men receiving ART (36.8) compared with those who did not (28.4) (absolute rate difference 4.7 cases per 1000 person-years). Multivariable analysis showed no statistical association between receiving ART and syphilis. Increased risk of syphilis was found in MSM aged 25–34 (HR 1.89, 95% CI 1.43 to 2.51) and in those diagnosed with two other STIs (HR 5.83, 95% CI 5.37 to 6.32).ConclusionWhile we observed a small increase in the rate of syphilis among those on ART, when adjusting for potential confounding factors, including a proxy measure for high-risk behaviour, there was no evidence of an increased risk of syphilis in MSM receiving ART. High-risk sexual behaviour markers were the main risk factors for syphilis, and our results highlight the need for STI prevention interventions in MSM living with HIV to target these particularly high-risk sexual networks.

Background.There is conflicting evidence about how HIV infection influences COVID-19. We compared the presentation characteristics and outcomes of people with and without HIV hospitalised with COVID-19 at 207 centres across the United Kingdom.Methods.We analysed data from people with laboratory confirmed or highly likely COVID-19 enrolled into the ISARIC CCP-UK study. The primary endpoint was day-28 mortality after presentation. We used Kaplan-Meier methods and Cox regression to describe the association with HIV status after adjustment for sex, ethnicity, age, indeterminate/probable hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, and presence/absence of ten comorbidities. We additionally adjusted for disease severity at presentation as defined by hypoxia/oxygen therapy.Findings.Among 47,539 patients, 115 (0·24%) had confirmed HIV-positive status and 103/115 (89·6%) had a record of antiretroviral therapy. At presentation, relative to the HIV-negative group, HIV-positive people were younger (median 55 versus 74 years; pInterpretation.HIV-positive status may be associated with an increased risk of day-28 mortality following a COVID-19 related hospitalisation.Funding.NIHR, MRC, Wellcome Trust, Department for International Development, Bill and Melinda Gates Foundation.Study registrationISRCTN66726260RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for articles in all languages containing the words “COVID*”, “coronavirus”, “SARS CoV-2” AND “HIV”. After screening on 23rd July 2020, we found 51 articles reporting outcomes of COVID-19 in HIV-positive people. Of these, 2 were systematic reviews, 24 were single case reports or case series of under 10 participants, and 12 were larger case series or retrospective cohorts without matched controls. There were two cohort studies that matched HIV-positive people diagnosed with COVID-19 to the general population attending for HIV care in the same area, and three studies that matched HIV-positive people diagnosed with COVID-19 to HIV-negative controls. Some of the evidence from the United States and Europe to date suggests that people with HIV experience a similar disease course and outcomes of COVID-19 compared to the general population. However, many of the studies are limited by small sample size, lack of comparator group and lack of adjustment for potential confounding. In contrast, preliminary results from a cohort study of over 20,000 participants in South Africa indicate that HIV-positive status more than doubles the risk of COVID-19 related mortality. Currently, the evidence from the United Kingdom is limited to two case series comprising a total of 21 patients.Added value of this studyThis study analysed data collected from 207 sites across the United Kingdom as part of ISARIC CCP, the largest prospective cohort of patients hospitalised with COVID-19, to evaluate the association between HIV-positive status and day-28 mortality. The study has the benefit of a relatively large number of participants with HIV (n=115, almost all receiving antiretroviral therapy) and importantly, the ability to direct compare their presenting characteristics and outcomes to those of 47,424 HIV-negative controls within the same dataset. This includes the ability to assess the influence of gender, ethnicity and age, as well as the effect of key comorbidities including chronic cardiac, pulmonary, renal and haematological disease, diabetes, obesity, chronic neurological disorder, dementia, liver disease, and malignancy. Unlike some of the other evidence to date, but in line with the data from South Africa, this study indicates that HIV-positive status may increase the risk of mortality with COVID-19 compared to the general population, with an effect that was especially evident among people with HIV aged below 60 years and was independent of gender or ethnicity. Although we detected an association between mortality among people with HIV and occurrence of obesity and diabetes with complication, the effect of HIV-positive status persisted after adjusting for comorbidities.Implications of all the available evidencePeople with HIV may be at increased risk of severe outcomes from COVID-19 compared to the general population. Ongoing data collection is needed to confirm this association. Linkage of hospital outcome data to the HIV history will be paramount to establishing the determinants of the increased risk. COVID-19 related hospitalisation should pursue systematic recording of HIV status to ensure optimal management and gathering of evidence.

BackgroundHIV treatment guidelines have traditionally recommended that all HIV-positive individuals are tested for evidence of drug resistance prior to starting ART. Testing for resistance to reverse transcriptase inhibitors and PIs is well established in routine care. However, testing for integrase strand transfer inhibitor (InSTI) resistance is less consistent.ObjectivesTo inform treatment guidelines by determining the prevalence of InSTI resistance in a national cohort of recently infected individuals.Patients and methodsRecent (within 4 months) HIV-1 infections were identified using a Recent Infection Testing Algorithm of new HIV-1 diagnoses in the UK. Resistance-associated mutations (RAMs) in integrase, protease and reverse transcriptase were detected by ultradeep sequencing, which allows for the sensitive estimation of the frequency of each resistant variant in a sample.ResultsThe analysis included 655 randomly selected individuals (median age = 33 years, 95% male, 83% MSM, 78% white) sampled in the period 2014 to 2016 and determined to have a recent infection. These comprised 320, 138 and 197 samples from 2014, 2015 and 2016, respectively. None of the samples had major InSTI RAMs occurring at high variant frequency (≥20%). A subset (25/640, 3.9%) had major InSTI RAMs occurring only as low-frequency variants (2%–20%). In contrast, 47/588 (8.0%) had major reverse transcriptase inhibitor and PI RAMs at high frequency.ConclusionsBetween 2014 and 2016, major InSTI RAMs were uncommon in adults with recent HIV-1 infection, only occurring as low-frequency variants of doubtful clinical significance. Continued surveillance of newly diagnosed patients for evidence of transmitted InSTI resistance is recommended to inform clinical practice.

Summary 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. Funding Public Health England.

OBJECTIVES: Reliable and timely HIV care cost estimates are important for policy option appraisals of HIV treatment and prevention strategies. As HIV clinical management and outcomes have changed, we aimed to update profiles of antiretroviral (ARV) usage pattern, patent/market exclusivity details and management costs in adults (≥ 18 years old) accessing HIV specialist care in England.METHODS: The data reported quarterly to the HIV and AIDS Reporting System in England was used to identify ARV usage pattern, and were combined with British National Formulary (BNF) prices, non-ARV care costs and patent/market exclusivity information to generate average survival-adjusted lifetime care costs. The cumulative budget impact from 2018 to the year in which all current ARVs were expected to lose market exclusivity was calculated for a hypothetical 85 000 (± 5000) person cohort, which provided an illustration of potential financial savings afforded by bioequivalent generic switches. Price scenarios explored BNF70 (September 2015) prices and generics at 10/20/30/50% of proprietary prices. The analyses took National Health Service (NHS) England's perspective (as the payer), and results are presented in 2016/2017 British pounds.RESULTS: By 2033, most currently available ARVs would lose market exclusivity; that is, generics could be available. Average per person lifetime HIV cost was ~£200 000 (3.5% annual discount) or ~£400 000 (undiscounted), reducing to ~£70 000 (3.5% annual discount; ~£120 000 undiscounted) with the use of generics (assuming that generics cost 10% of proprietary prices). The cumulative budget to cover 85 000 (± 5000) persons for 16 years (2018-2033) was £10.5 (± 0.6) billion, reducing to £3.6 (± 0.2) billion with the use of generics.CONCLUSIONS: HIV management costs are high but financial efficiency could be improved by optimizing generic use for treatment and prevention to mitigate the high cost of lifelong HIV treatment. Earlier implementation of generics as they become available offers the potential to maximize the scale of the financial savings.

BACKGROUND: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient. METHODS: Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%. Sequence alignments including >110 000 HIV-1 partial pol consensus sequences from the UK HIV Drug Resistance Database (UK-HDRD), linked to epidemiological and clinical data from the HIV and AIDS Reporting System, were used for transmission cluster analysis. Transmission clusters were identified using Cluster Picker with a clade support of >90% and maximum genetic distances of 4.5% or 1.5%, the latter to limit detection to likely direct transmission events. RESULTS: Drug-resistant majority variants (DRMajVs) were detected in 66 (7.9%) and DRMinVs in 84 (10.1%) of the recently infected individuals. High levels of clustering to sequences in UK-HDRD were observed for both DRMajV (n = 48; 72.7%) and DRMinV (n = 63; 75.0%) sequences. Of these, 43 (65.2%) with DRMajVs were in a transmission cluster with sequences that harbored the same DR mutation compared to only 3 (3.6%) sequences with DRMinVs (P < .00001, Fisher exact test). Evidence of likely direct transmission of DRMajVs was observed for 25/66 (37.9%), whereas none were observed for the DRMinVs (P < .00001). CONCLUSIONS: Using a densely sampled HIV-infected population, we show no evidence of DRMinV transmission among recently infected individuals.

Background. The United Kingdom human immunodeficiency virus (HIV) epidemic was historically dominated by HIV subtype B transmission among men who have sex with men (MSM). Now 50% of diagnoses and prevalent infections are among heterosexual individuals and mainly involve non-B subtypes. Between 2002 and 2010, the prevalence of non-B diagnoses among MSM increased from 5.4% to 17%, and this study focused on the drivers of this change. Methods. Growth between 2007 and 2009 in transmission clusters among 14 000 subtype A1, C, D, and G sequences from the United Kingdom HIV Drug Resistance Database was analysed by risk group. Results. Of 1148 clusters containing at least 2 sequences in 2007, >75% were pairs and >90% were heterosexual. Most clusters (71.4%) did not grow during the study period. Growth was significantly lower for small clusters and higher for clusters of ≥7 sequences, with the highest growth observed for clusters comprising sequences from MSM and people who inject drugs (PWID). Risk group (P < .0001), cluster size (P < .0001), and subtype (P < .01) were predictive of growth in a generalized linear model. Discussion. Despite the increase in non-B subtypes associated with heterosexual transmission, MSM and PWID are at risk for non-B infections. Crossover of subtype C from heterosexuals to MSM has led to the expansion of this subtype within the United Kingdom.

Background Despite a decline in the number of new HIV infections in the UK overall, the number and proportion of new HIV diagnoses in people aged ≥50 years continues to increase. People aged ≥50 years are disproportionately affected by late diagnosis, which is associated with poorer health outcomes, increased treatment complexity and increased healthcare costs. Late HIV diagnosis also has significant public health implications in terms of onward HIV transmission. It is not fully understood what factors affect the decision of an older person to test for HIV. The aim of this study was to identify factors associated with testing for HIV in people aged ≥50 years who tested late for HIV. Methods We interviewed 20 people aged ≥50 years diagnosed late with HIV to identify factors associated with HIV testing. Interviews were audio recorded, transcribed verbatim and thematically analysed. Results Seven themes associated with HIV testing in people aged ≥50 years were identified: experience of early HIV/AIDS campaigns, HIV knowledge, presence of symptoms and symptom attribution, risk and risk perception, generational approaches to health and sexual health, stigma, and type of testing and testing venue. Conclusion Some factors associated with testing identified in this study were unique to older individuals. People aged ≥50 years often do not perceive themselves to be at risk of HIV. Further, stigma and a lack of knowledge of how to access HIV testing suggest a need for health promotion and suggest current sexual health services may need to adapt to better meet their needs.

BackgroundNear 60% of new HIV infections in the United Kingdom are estimated to occur in men who have sex with men (MSM). Patterns of mixing between different risk groups of MSM have been suggested to spread the HIV epidemics through age-disassortative partnerships and to contribute to ethnic disparities in infection rates. Understanding these mixing patterns in transmission can help to determine which groups are at a greater risk and guide prevention.MethodsWe analyzed combined epidemiologic data and viral sequences from MSM diagnosed with HIV as of mid-2015 at the national level. We applied a phylodynamic source attribution model to infer patterns of transmission between groups of patients by age, ethnicity and region.ResultsFrom pair probabilities of transmission between 19 847 MSM patients, we found that potential transmitters of HIV subtype B were on average 5 months older than recipients. We also found a moderate overall assortativity of transmission by ethnic group and a stronger assortativity by region.ConclusionsOur findings suggest that there is only a modest net flow of transmissions from older to young MSM in subtype B epidemics and that young MSM, both for Black or White groups, are more likely to be infected by one another than expected in a sexual network with random mixing.

OBJECTIVES: The aim of the study was to measure and compare national continuum of HIV care estimates in Europe and Central Asia in three key subpopulations: men who have sex with men (MSM), people who inject drugs (PWID) and migrants. METHODS: Responses to a 2016 European Centre for Disease Prevention and Control (ECDC) survey of 55 European and Central Asian countries were used to describe continuums of HIV care for the subpopulations. Data were analysed using three frameworks: Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; breakpoint analysis identifying reductions between adjacent continuum stages; quadrant analysis categorizing countries using 90% cut-offs for continuum stages. RESULTS: Overall, 29 of 48 countries reported national data for all HIV continuum stages (numbers living with HIV, diagnosed, receiving treatment and virally suppressed). Six countries reported all stages for MSM, seven for PWID and two for migrants. Thirty-one countries did not report data for MSM (34 for PWID and 41 for migrants). In countries that provided key-population data, overall, 63%, 40% and 41% of MSM, PWID and migrants living with HIV were virally suppressed, respectively (compared with 68%, 65% and 68% nationally, for countries reporting key-population data). Variation was observed between countries, with higher outcomes in subpopulations in Western Europe compared with Eastern Europe and Central Asia. CONCLUSIONS: Few reporting countries can produce the continuum of HIV care for the three key populations. Where data are available, differences exist in outcomes between the general and key populations. While MSM broadly mirror national outcomes (in the West), PWID and migrants experience poorer treatment and viral suppression. Countries must develop continuum measures for key populations to identify and address inequalities.

Objectives Our objective was to present recent trends in the UK HIV epidemic (2007-2016) and the public health response. Methods HIV diagnoses and clinical markers were extracted from the HIV and AIDS Reporting System; HIV testing data in sexual health services (SHS) were taken from GUMCAD STI Surveillance System. HIV data were modelled to estimate the incidence in men who have sex with men (MSM) and post-migration HIV acquisition in heterosexuals. Office for National Statistics (ONS) data enabled mortality rates to be calculated. Results New HIV diagnoses have declined in heterosexuals as a result of decreasing numbers of migrants from high HIV prevalence countries entering the UK. Among MSM, the number of HIV diagnoses fell from 3570 in 2015 to 2810 in 2016 (and from 1554 to 1096 in London). Preceding the decline in HIV diagnoses, modelled estimates indicate that transmission began to fall in 2012, from 2800 [credible interval (CrI) 2300-3200] to 1700 (CrI 900-2700) in 2016. The crude mortality rate among people promptly diagnosed with HIV infection was comparable to that in the general population (1.22 vs. 1.39 per 1000 aged 15-59 years, respectively). The number of MSM tested for HIV at SHS increased annually; 28% of MSM who were tested in 2016 had been tested in the preceding year. In 2016, 76% of people started antiretroviral therapy within 90 days of diagnosis (33% in 2007). Conclusions The dual successes of the HIV transmission decline in MSM and reduced mortality are attributable to frequent HIV testing and prompt treatment (combination prevention). Progress towards the elimination of HIV transmission, AIDS and HIV-related deaths could be achieved if combination prevention, including pre-exposure prophylaxis, is replicated for all populations.

Prompt linkage to human immunodeficiency virus (HIV) care after diagnosis is crucial to ensure optimal patient outcomes. However, few countries monitor this important public health marker and different definitions have been applied, making country and study comparisons difficult. This article presents an expert-agreed, standard definition of linkage to care for a pragmatic approach to public health monitoring, appropriate to the European context. Here, linkage to care is defined as patient entry into specialist HIV care after diagnosis, measured as the time between the HIV diagnosis date and one of the following markers: either the first clinic attendance date, first CD4+ cell count or viral load date, or HIV treatment start date, depending on data availability; Linkage is considered prompt if within 3 months of diagnosis. Application of this definition by researchers and public health professionals when reporting surveillance or research data relating to linkage to care after HIV diagnosis will enable reliable comparisons across countries, better assessment of the success of health services programmes aimed at improving peoples access to HIV treatment and care and the identification of barriers limiting access to HIV care across Europe.

Summary Background Many people with HIV are undiagnosed. Early diagnosis saves lives and reduces onward transmission. We assessed whether an education programme promoting rapid HIV testing in general practice would lead to increased and earlier HIV diagnosis. Methods In this cluster randomised controlled trial in Hackney (London, UK), general practices were randomly assigned (1:1) to offer either opt-out rapid HIV testing to newly registering adults or continue usual care. All practices were invited to take part. Practices were randomised by an independent clinical trials unit statistician with a minimisation program, maintaining allocation concealment. Neither patients nor investigators were masked to treatment allocation. The primary outcome was CD4 count at diagnosis. Secondary outcomes were rate of diagnosis, proportion with CD4 count less than 350 cells per μL, and proportion with CD4 count less than 200 cells per μL. This study is registered with ClinicalTrials.gov, number ISRCTN63473710. Findings 40 of 45 (89%) general practices agreed to participate: 20 were assigned to the intervention group (44 971 newly registered adult patients) and 20 to the control group (38 464 newly registered adult patients), between April 19, 2010, and Aug 31, 2012. Intervention practices diagnosed 32 people with HIV versus 14 in control practices. Mean CD4 count at diagnosis was 356 cells per μL (SD 254) intervention practices versus 270 (SD 257) in control practices (adjusted difference of square root CD4 count 3·1, 95% CI −1·2 to 7·4; p=0·16);); in a pre-planned sensitivity analysis excluding patients diagnosed via antenatal care, the difference was 6·4 (95% CI, 1·2 to 11·6; p=0·017). Rate of HIV diagnosis was 0·30 (95% CI 0·11 to 0·85) per 10 000 patients per year in intervention practices versus 0·07 (0·02 to 0·20) in control practices (adjusted ratio of geometric means 4·51, 95% CI 1·27 to 16·05; p=0·021). 55% of patients in intervention practices versus 73% in control practices had CD4 count less than 350 cells per μL (risk ratio 0·75, 95% CI 0·53 to 1·07). 28% versus 46% had CD4 count less than 200 cells per μL (0·60, 0·32 to 1·13). All patients diagnosed by rapid testing were successfully transferred into specialist care. No adverse events occurred. Interpretation Promotion of opt-out rapid testing in general practice led to increased rate of diagnosis, and might increase early detection, of HIV. We therefore recommend implementation of HIV screening in general practices in areas with high HIV prevalence. Funding UK Department of Health, NHS City and Hackney.

Patients who do not disclose their sexuality, including men who do not disclose same-sex behaviour, are difficult to characterise through traditional epidemiological approaches such as interviews. Using a recently developed method to detect large networks of viral sequences from time-resolved trees, we localised non-disclosed men who have sex with men (MSM) in UK transmission networks, gaining crucial insight into the behaviour of this group.For this phylogenetic analysis, we obtained HIV pol sequences from the UK HIV Drug Resistance Database (UKRDB), a central repository for resistance tests done as part of routine clinical care throughout the UK. Sequence data are linked to demographic and clinical data held by the UK Collaborative HIV Cohort study and the national HIV/AIDS reporting system database. Initially, we reconstructed maximum likelihood phylogenies from these sequences, then sequences were selected for time-resolved analysis in BEAST if they were clustered with at least one other sequence at a genetic distance of 4·5% or less with support of at least 90%. We used time-resolved phylogenies to create networks by linking together nodes if sequences shared a common ancestor within the previous 5 years. We identified potential non-disclosed MSM (pnMSM), defined as self-reported heterosexual men who clustered only with men. We measured the network position of pnMSM, including betweenness (a measure of connectedness and importance) and assortativity (the propensity for nodes sharing attributes to link).14 405 individuals were in the network, including 8452 MSM, 1743 heterosexual women and 1341 heterosexual men. 249 pnMSM were identified (18·6% of all clustered heterosexual men) in the network. pnMSM were more likely to be black African (p0·0001), less likely to be infected with subtype B (p=0·006), and were slightly older (p=0·002) than the MSM they clustered with. Mean betweenness centrality was lower for pnMSM than for MSM (1·31, 95% CI 0·48-2·15 in pnMSM vs 2·24, 0·98-3·51 in MSM; p=0·002), indicating that pnMSM were in peripheral positions in MSM clusters. Assortativity by risk group was higher than expected (0·037 vs -0·037, p=0·01) signifying that pnMSM were linked to each other. We found that self-reported heterosexual men were more likely to link MSM and heterosexual women than heterosexual women were to link MSM and heterosexual men (Fisher's exact test p=0·0004; OR 2·24) but the number of such transmission chains was small (only 54 in total vs 32 in women).pnMSM are a subgroup distinct from both MSM and from heterosexual men. They are more likely to choose sexual partners who are also pnMSM and might exhibit lower-risk sexual behaviour than MSM (eg, choosing low-risk partners or consistently using condoms). Heterosexual men are the group most likely to be diagnosed with late-stage disease (ie, low CD4 counts) and non-disclosed MSM might put female partners at higher risk than heterosexual men because non-disclosed MSM have male partners. Hence, pnMSM require specific consideration to ensure they are included in public health interventions.National Institutes of Health.

Since October 2015 up to September 2016, HIV diagnoses fell by 32% compared with October 2014–September 2015 among men who have sex with men (MSM) attending selected London sexual health clinics. This coincided with high HIV testing volumes and rapid initiation of treatment on diagnosis. The fall was most apparent in new HIV testers. Intensified testing of high-risk populations, combined with immediately received anti-retroviral therapy and a pre-exposure prophylaxis (PrEP) programme, may make elimination of HIV achievable.

We report on measures used to monitor the response to the UK HIV epidemic. We present analyses of routine data on HIV testing, diagnosis and care, and of CD4 back-calculation models to estimate country of HIV acquisition and incidence. Over the past decade, HIV and AIDS diagnoses and deaths declined while HIV testing coverage increased. Linkage into care, retention in care, and viral suppression was high with few socio-demographic differences. However, in 2013, incidence among MSM, and undiagnosed infection, also remained high, and more than half of heterosexuals newly diagnosed with HIV (the majority of whom were born-abroad) probably acquired HIV in the UK and were diagnosed late. HIV care following diagnosis is excellent in the UK. Improvements in testing and prevention are required to reduce undiagnosed infection, incidence and late diagnoses. Routinely collected laboratory and clinic data is a low cost, robust and timely mechanism to monitor the public health response to national HIV epidemics.

Objectives Prompt HIV diagnosis and treatment are associated with increased longevity and reduced transmission. The aim of the study was to examine late diagnoses and to assess the quality of care following diagnosis. Methods National surveillance and cohort data were used to examine late HIV diagnoses and to assess the quality of care received in the 12 months following HIV diagnosis. Results In 2011, 79% (4910/6219) of persons (15 years and over) diagnosed with HIV infection had CD4 counts reported within 3 months; of these, 49% were diagnosed late (CD4 count < 350 cells/μL). Adults aged 50 years and over were more likely to be diagnosed late (67%) compared with those aged 15–24 years (31%). Sixty-four per cent of heterosexual men were diagnosed late compared with 46% of women and 36% of men who have sex with men (MSM) (P < 0.01). The percentage of late diagnoses was highest among black African adults (66%) compared with other ethnicities; 96% of black African adults diagnosed late were born abroad. Overall, 88% and 97% of patients were linked to care within 1 and 3 months of diagnosis, respectively, with little variation by demographics and exposure category. The crude 1-year mortality rate was 31.6 per 1000 persons diagnosed in 2010. It was highest among adults diagnosed late (40.3/1000 versus 5.2/1000 for prompt diagnoses) and particularly among those aged 50 years and over. Excluding deaths, 85% of the 5833 diagnosed in 2010 were retained in care in 2011; 92% of the 2264 adults diagnosed late in 2010 received antiretroviral therapy by the end of 2011. Conclusions The National Health Service provides high-quality care to persons newly diagnosed with HIV infection in the UK, with no evidence of health inequalities. Despite excellent care, half of adults are diagnosed late according to the threshold at which national guidelines recommend treatment should begin. Such patients have an 8-fold increased risk of 1-year mortality compared with those diagnosed promptly. Reducing late diagnosis of HIV infection remains a public health priority in the UK.

Objectives In the UK, free HIV care is provided through dedicated HIV clinics. Using the national cohort of men who have sex with men (MSM) with diagnosed HIV infection and estimates of the number of undiagnosed men, we assessed whether high retention in HIV care and treatment coverage is sufficient to reduce HIV transmission. Methods Antiretroviral therapy (ART) uptake and viral load distribution among diagnosed men were analysed by treatment status and CD4 count for the period between 2006 and 2010. A multi-parameter evidence synthesis (MPES) method was used to estimate the size of the undiagnosed population. The viral load distribution among newly diagnosed untreated men was applied to the undiagnosed population. Infectivity was defined as a viral load > 1500 HIV-1 RNA copies/mL. Results Between 2006 and 2010, ART coverage among all HIV-infected MSM (diagnosed and undiagnosed) increased from 49 to 60%, while the proportion of infectious men fell from 47 to 35%. Over the same period, the number of all HIV-infected MSM increased from 30 000 to 40 100 and the number of infectious MSM remained stable at 14 000. Of the 14 000 infectious MSM in 2010, 62% were undiagnosed, 33% were diagnosed but untreated, and 5% received ART. Extending ART to all diagnosed HIV-infected MSM with CD4 counts

BACKGROUND: HIV transmission in men who have sex with men (MSM) in the UK has shown no sign of decreasing in the past decade. Additional prevention measures are needed. We aimed to estimate the effect of various potential interventions implemented individually and in combination on prevention of HIV infection. METHODS: We extended a deterministic partnership-based mathematical model for HIV transmission, informed by detailed behavioural and surveillance data, to assess the effect of seven different HIV interventions implemented in MSM (aged 15-64 years) in the UK during 2014-20, including increasing rates of HIV testing, test-and-treat programmes, pre-exposure prophylaxis (PrEP), and sexual behavioural changes. We did sensitivity analyses on risk compensation. FINDINGS: We predicted a baseline of 16 955 new infections (IQR 13 156-21 669) in MSM in the UK during 2014-20. At a coverage of ≤50%, testing twice a year outperformed all other interventions. Of all intervention combinations, only the combined effect of test and treat and annual HIV testing (61·8%, IQR 47·2-81·8, of total incidence) was greater than the sum of effects of the two interventions individually (32·6%, 23·7-46·0, and 23·9%, 16·5-33·3, respectively). Simultaneous PrEP, expansion of HIV testing, and initiation of test-and-treat programme in 25% of high-activity MSM could save 7399 (IQR 5587-9813) UK MSM from HIV infection (43·6%, IQR 32·9-57·9, of total incidence). An increase in unsafe sex or sexual partners to 50% or more could substantially reduce the effect of interventions, but is unlikely to negate the prevention benefit completely. INTERPRETATION: PrEP could prevent a large number of new HIV infections if other key strategies including HIV testing and treatment are simultaneously expanded and improved. Without PrEP, HIV incidence in MSM in the UK is unlikely to decrease substantially by the end of this decade. FUNDING: Health Protection Agency (now Public Health England)., Health Protection Agency (now Public Health England).

The WHO guidelines recommend antiretroviral therapy (ART) begins when CD4 cell counts reach less than 500 cells to reduce HIV transmission. In the UK, 96 000 people were living with HIV (PLWHIV) in 2011, ART coverage was 84% among the diagnosed population and 42% of PLWHIV had detectable viraemia. Using published methods, we estimate starting ART at below 500 CD4 cells could have reduced the proportion of PLWHIV with detectable viraemia from 42% to 38%, whereas halving the undiagnosed population could have led to a decrease to 28%. In the UK, it is unlikely early treatment will reduce HIV transmission unless the undiagnosed population is substantially reduced.

IntroductionHIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets).Methods and analysisService evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses.Ethics and disseminationThe chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners.

Whether the incidence of tuberculosis in HIV-positive people receiving long-term antiretroviral therapy (ART) remains above background population rates is unclear. We compared tuberculosis incidence in people receiving ART with background rates in England, Wales, and Northern Ireland.We analysed a national cohort of HIV-positive individuals linked to the national tuberculosis register. Tuberculosis incidence in the HIV-positive cohort (2007-11) was stratified by ethnic origin and time on ART and compared with background rates (2009). Ethnic groups were defined as follows: the black African group included all individuals of black African origin, including those born in the UK and overseas; the white ethnic group included all white individuals born in the UK and overseas; the south Asian group included those of Indian, Pakistani, and Bangladeshi origin, born in the UK and overseas; and the other ethnic group included all other ethnic origins, including black Afro-Caribbeans.The HIV-positive cohort comprised 79 919 individuals, in whom there were 1550 incident cases in 231 664 person-years of observation (incidence 6·7 cases per 1000 person-years). Incidence of tuberculosis in the HIV-positive cohort was 13·6 per 1000 person-years in black Africans and 1·7 per 1000 person-years in white individuals. Incidence of tuberculosis during long-term ART (≥5 years) in black Africans with HIV was 2·4 per 1000 person-years, similar to background rates of 1·9 per 1000 person-years in this group (rate ratio 1·2, 95% CI 0·96-1·6; p=0·083); but in white individuals with HIV on long-term ART the incidence of 0·5 per 1000 person-years was higher than the background rate of 0·04 per 1000 person-years (rate ratio 14·5, 9·4-21·3; p0·0001). The increased incidence relative to background in white HIV-positive individuals persisted when analysis was restricted to person-time accrued on ART with CD4 counts of at least 500 cells per μL and when white HIV-positive individuals born abroad were excluded.Tuberculosis incidence is unacceptably high irrespective of HIV status in black Africans. In white individuals with HIV, tuberculosis incidence is significantly higher than background rates in white people despite long-term ART. Expanded testing and treatment for latent tuberculosis infection to all HIV-infected adults, irrespective of ART status and CD4 cell count, might be warranted.Public Health England.

Arie reported the extent to which migrant patients are a drain on NHS resources.1 The problem of HIV tourism by people who are known to be infected with HIV is minimal. Moreover, whereas some visitors are tested for HIV at sexually transmitted disease (STD) clinics, the numbers are modest and early diagnosis and treatment reduces the costs of care and infectiousness. Of 65 240 adults seen for HIV …

The United Kingdom’s CD4 surveillance scheme monitors CD4 cell counts among HIV patients and is a national resource for HIV surveillance. It has driven public health policy and allowed auditing of national HIV testing, treatment and care guidelines.We demonstrate its utility through four example outputs: median CD4 count at HIV diagnosis; late HIV diagnosis and short-term mortality; the timing of first CD4 count to indicate entry into HIV care; and the proportion of patients with CD4 counts In 2009, 95% (61,502/64,420) of adults living with diagnosed HIV infection had CD4 counts available. The median CD4 count at diagnosis increased from 276 to 335 cells/mm3 between 2000 and 2009, indicating modest improvements in HIV testing. In 2009, 52% of patients were diagnosed at a late stage of HIV infection (CD4 3); these individuals had a ten-fold risk of dying within a year of their diagnosis compared to those diagnosed promptly. In 2008, the national target of performing a CD4 count within 14 days of diagnosis was met for 61% of patients. National treatment guidelines have largely been met with 83% patients with CD4 3receiving ARV.The monitoring of CD4 counts is critical to HIV surveillance in the United Kingdom enabling the close monitoring of efforts to reduce morbidity and mortality associated with late diagnosis and underpins the auditing of policies and guidelines. These routine surveillance outputs can be generated at national and local levels to drive and monitor public health policy and prevention efforts.

Background/introduction As in many other western countries, men who have sex with men (MSM) are most affected by HIV in the UK. Aim(s)/objectives To describe 15-year trends in HIV among MSM to inform prevention strategies. Methods National HIV surveillance data were linked to national register deaths and HIV testing data from sexually transmitted infection (STI) clinics. Multivariable analyses revealed predictors of late diagnosis (800 men have been diagnosed late annually since 2004. HIV testing in STI clinics in England increased, 10,900 to 102,600. One-year death rates among new diagnoses declined (4.6% to 0.9%) due to fewer deaths among late presenters (4.4% to 1.8%). Older age (>50) and living outside London were predictors of late presentation, while older age and late presentation were predictors of one-year mortality. Discussion/conclusion In its third decade, the HIV epidemic among UK MSM has continued to diversify. Increases in new diagnoses reflect both increased testing and ongoing transmission. Despite improvements in patient outcomes, >800 men present late each year; death rates remain high and preventable. Culturally appropriate prevention and testing strategies require strengthening to reduce HIV transmission and late diagnosis.

Background Regular clinical care is important for the well-being of people with HIV. We sought to audit and describe the characteristics of adults with diagnosed HIV infection not reported to be attending for clinical care in the UK. Methods Public Health England (PHE) provided clinics with lists of patients diagnosed or seen for specialist HIV care in 2010 but not linked to a clinic report or known to have died in 2011. Clinics reviewed case-notes of these individuals and completed questionnaires. A nested case–control analysis was conducted to compare those who had remained in the UK in 2011 while not attending care with individuals who received specialist HIV care in both 2010 and 2011. Results Among 74,418 adults living with diagnosed HIV infection in the UK in 2010, 3510 (4.7 %) were not reported as seen for clinical care or died in 2011. Case note reviews and outcomes were available for 2255 (64 %) of these: 456 (20.2 %) remained in the UK and did not attend care; 590 (26.2 %) left UK; 508 (22.6 %) received care in the UK: 73 (3.2 %) died and 628 (27.8 %) had no documented outcome. Individuals remaining in the UK and not attending care were more likely to be treatment naïve than those in care, but duration since HIV diagnosis was not significant. HIV/AIDS related hospitalisations were observed among non-attenders. Conclusion Retention in UK specialist HIV care is excellent. Our audit indicates that the ‘true’ loss to follow up rate in 2011 was