Re-assessing the late HIV diagnosis surveillance definition in the era of increased and frequent testing.

OBJECTIVES: Late HIV diagnosis (CD4 <350 cells/mm3 ) is a key public health metric. In an era of more frequent testing, the likelihood of HIV diagnosis occurring during seroconversion, when CD4 counts may dip below 350, is greater. We applied a correction, considering markers of recent infection, and re-assessed 1-year mortality following late diagnosis. METHODS: We used national epidemiological and laboratory surveillance data from all people diagnosed with HIV in England, Wales, and Northern Ireland (EW&NI). Those with a baseline CD4 <350 were reclassified as 'not late' if they had evidence of recent infection (recency test and/or negative test within 24 months). A correction factor (CF) was the number reclassified divided by the number with a CD4 <350. RESULTS: Of the 32 227 people diagnosed with HIV in EW&NI between 2011 and 2019 with a baseline CD4 (81% of total), 46% had a CD4 <350 (uncorrected late diagnosis rate): 34% of gay and bisexual men (GBM), 65% of heterosexual men, and 56% of heterosexual women. Accounting for recency test and/or prior negative tests gave a 'corrected' late diagnosis rate of 39% and corresponding CF of 14%. The CF increased from 10% to 18% during 2011-2015, then plateaued, and was larger among GBM (25%) than heterosexual men and women (6% and 7%, respectively). One-year mortality among people diagnosed late was 329 per 10 000 after reclassification (an increase from 288/10 000). CONCLUSIONS: The case-surveillance definition of late diagnosis increasingly overestimates late presentation, the extent of which differs by key populations. Adjustment of late diagnosis is recommended, particularly for frequent testers such as GBM.

Late diagnosis of HIV: An updated consensus definition.

INTRODUCTION: In recent years, HIV testing frequency has increased, resulting in more people being diagnosed during seroconversion with a temporarily low CD4 count. Using the current consensus definition of late HIV presentation ('presenting for care with a CD4 count < 350 cells/µL or an AIDS-defining event, regardless of CD4 count') these individuals would be incorrectly assigned as being diagnosed late. METHODS: In spring 2022, a European expert group convened to revise the current late HIV presentation consensus definition. A survey on data availability to apply this revised definition was sent to nominated European focal points responsible for HIV surveillance (n = 53). RESULTS: Experts agreed that the updated definition should refer to late HIV diagnosis rather than presentation and include the following addition: People with evidence of recent infection should be reclassified as 'not late', with evidence of recent infection considered hierarchically. The individual must have: (i) laboratory evidence of recent infection; (ii) a last negative HIV test within 12 months of diagnosis; or (iii) clinical evidence of acute infection. People with evidence of being previously diagnosed abroad should be excluded. A total of 18 countries responded to the survey; 83% reported capturing CD4 count and/or AIDS at diagnosis through national surveillance, 67% captured last negative test and/or previous HIV diagnosis, 61% captured seroconversion illness at diagnosis and 28% captured incident antibody results. CONCLUSIONS: Accurate data on late diagnosis are important to describe the effects of testing programmes. Reclassification of individuals with recent infection will help to better identify populations most at risk of poor HIV outcomes and areas for intervention.

Invasive Pneumococcal Disease in People With Human Immunodeficiency Virus in England, 1999-2017.

BACKGROUND: The 7-valent and 13-valent pneumococcal conjugate vaccines (PCVs) were introduced into the UK childhood immunization program in 2006 and 2010, respectively, with high effectiveness and resulting in both direct and indirect protection. We describe the epidemiology of invasive pneumococcal disease (IPD) in adults with human immunodeficiency virus (HIV) in England following the introduction of both PCVs. METHODS: Data on a national cohort of people with HIV were linked to confirmed IPD cases in adults aged ≥ 15 years during 1999-2017. Date of HIV infection was estimated using a CD4 slope decline algorithm. RESULTS: Among 133 994 adults with HIV, 1453 developed IPD during 1999-2017, with 70% (1016/1453) developing IPD ≥ 3 months after their HIV diagnosis. IPD and HIV were codiagnosed within 90 days in 345 (24%) individuals. A missed opportunity for earlier HIV diagnosis was identified in 6% (89/1453), mostly in earlier years. IPD incidence in people with HIV increased from 147/100 000 in 1999 to 284/100 000 in 2007 before declining and stabilizing between 92 and 113/100 000 during 2014-2017. Mean annual IPD incidence was lower among those receiving antiretroviral therapy during 2014-17 (68 vs 720/100 000; incidence rate ratio [IRR] 9.3; 95% confidence interval [CI], 7.3-11.8; P < .001) and was markedly lower in those with a suppressed viral load (50 vs 523/100 000; IRR 10.4; 95% CI, 7.6-14.1; P < .001). The latter group still had 4.5-fold higher (95% CI, 3.8-5.3; P < .001) IPD incidence compared to the general population (11.2/100 000). CONCLUSIONS: IPD incidence among people with HIV reduced after PCV13 introduction and has remained stable. Adults presenting with IPD should continue to be tested for HIV infection.

Post-migration acquisition of HIV: Estimates from four European countries, 2007 to 2016.

BackgroundThe assumption that migrants acquire human immunodeficiency virus (HIV) before migration, particularly those from high prevalence areas, is common.AimWe assessed the place of HIV acquisition of migrants diagnosed in four European countries using surveillance data.MethodsUsing 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.ResultsBetween 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).ConclusionsMigrants, 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.

Extending Bayesian back-calculation to estimate age and time specific HIV incidence.

CD4-based multi-state back-calculation methods are key for monitoring the HIV epidemic, providing estimates of HIV incidence and diagnosis rates by disentangling their inter-related contribution to the observed surveillance data. This paper, extends existing approaches to age-specific settings, permitting the joint estimation of age- and time-specific incidence and diagnosis rates and the derivation of other epidemiological quantities of interest. This allows the identification of specific age-groups at higher risk of infection, which is crucial in directing public health interventions. We investigate, through simulation studies, the suitability of various bivariate splines for the non-parametric modelling of the latent age- and time-specific incidence and illustrate our method on routinely collected data from the HIV epidemic among gay and bisexual men in England and Wales.

HIV in Europe and Central Asia: progress in 2018 towards meeting the UNAIDS 90-90-90 targets.

In 2018, 52 of 55 European and Central Asian countries reported data against the UNAIDS 90-90-90 targets. Overall, 80% of people living with HIV (PLHIV) were diagnosed, of whom 64% received treatment and 86% treated were virally suppressed. Subregional outcomes varied: West (87%-91%-93%), Centre (83%-73%-75%) and East (76%-46%-78%). Overall, 43% of all PLHIV were virally suppressed; intensive efforts are needed to meet the 2020 target of 73%.

Defining linkage to care following human immunodeficiency virus (HIV) diagnosis for public health monitoring in Europe.

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.

Monitoring of the HIV Epidemic Using Routinely Collected Data: The Case of the United Kingdom.

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.

Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?

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.

Recommendations for defining preventable HIV-related mortality for public health monitoring in the era of Getting to Zero: an expert consensus.

Getting to Zero is a commonly cited strategic aim to reduce mortality due to both HIV and avoidable deaths among people with HIV. However, no clear definitions are attached to these aims with regard to what constitutes HIV-related or preventable mortality, and their ambition is limited. This Position Paper presents consensus recommendations to define preventable HIV-related mortality for a pragmatic approach to public health monitoring by use of national HIV surveillance data. These recommendations were informed by a comprehensive literature review and agreed by 42 international experts, including clinicians, public health professionals, researchers, commissioners, and community representatives. By applying the recommendations to 2019 national HIV surveillance data from the UK, we show that 30% of deaths among people with HIV were HIV-related or possibly HIV-related, and at least 63% of these deaths were preventable or potentially preventable. The application of these recommendations by health authorities will ensure consistent monitoring of HIV elimination targets and allow for the identification of inequalities and areas for intervention.

Loss to follow-up among adults attending human immunodeficiency virus services in England, Wales, and Northern Ireland.

AIM: To assess the extent to which human immunodeficiency virus (HIV)-diagnosed adults attending HIV-services in England, Wales, and Northern Ireland are lost to follow-up or attend services intermittently. METHODS: A cohort of HIV-diagnosed adults was created by linking records across the 1998 to 2007 national annual Survey of Prevalent HIV Infections Diagnosed. The records were also linked to the national HIV and acquired immune deficiency syndrome New Diagnoses Database (n = 61,495) and to Office for National Statistics death records. Patterns of HIV-service attendance were analyzed. RESULTS: On average, 90% of adults attending HIV-services in any one year attended the following year. Nearly 5% of adults attending services in any one year were lost to follow-up, a further 4% subsequently attended services intermittently, whereas less than 2% died. Cumulatively, 19% of adults seen for HIV care between 1998 and 2006 were lost to follow-up by the end of 2007. Factors associated with loss to follow-up included being the following: female; aged 15 to 34 years; black-African or "other" ethnicity; not on antiretroviral therapy; recently diagnosed; and infected outside the United Kingdom. CONCLUSIONS: Although the majority of HIV-diagnosed adults in England, Wales, and Northern Ireland attended HIV-services regularly, cumulatively nearly 1 in 5 adults were lost to follow-up between 1998 and 2007. Innovative strategies focusing on those most likely to drop out of regular care should be developed to maintain regular service engagement and to ensure optimal care.

Tracking elimination of HIV transmission in men who have sex with men in England: a modelling study.

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.

Trends in undiagnosed HIV prevalence in England and implications for eliminating HIV transmission by 2030: an evidence synthesis model.

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.

HIV counselling and testing in Nova Scotia: the provincial strategy in the context of an international debate.

Nova Scotia, as a small province in Atlantic Canada, provides health care professionals and policy analysts with unique challenges for developing and implementing a strategy for accessible and acceptable HIV counselling and testing. Despite universal health care in Canada, barriers and challenges persist in relation to HIV counselling and testing programs and services in Nova Scotia. It is therefore necessary to examine the unique circumstances in the provision of programs and services in Nova Scotia prior to the possibility of adopting international HIV counselling and testing standards and guidelines being implemented in other jurisdictions. Nova Scotia's provincial strategy on HIV/AIDS promotes a harm-reduction approach for different populations in various service settings, recognizing the diverse circumstances and experiences of people living in Nova Scotia. By contrast, the Centers for Disease Control (CDC) recommended strategy promotes opt-out testing and in some instances alters the requirement of informed consent. As the Public Health Agency of Canada (PHAC) revises the national HIV counselling and testing policies, it is imperative to address the unique characteristics of Nova Scotia's provision of services, and how divergent strategies have the potential to address or compound the barriers to access that exist in this province's communities.

The late diagnosis and consequent short-term mortality of HIV-infected heterosexuals (England and Wales, 2000-2004).

OBJECTIVES: To describe the proportion of HIV-infected heterosexual individuals diagnosed late and estimate how much mortality could have been prevented by earlier diagnosis. DESIGN: A population-based study using surveillance reports from England and Wales. METHODS: Calculation of proportions diagnosed late (CD4 cell count < 200 cells/mul) and short-term mortality (death within a year of diagnosis). RESULTS: A total of 16 375 heterosexual individuals were diagnosed with HIV (2000-2004): 10 503 with CD4 cell counts available at that time; 42% (4425) were diagnosed late. Late diagnosis increased with age (P < 0.01). One fifth of women diagnosed antenatally were diagnosed late compared with 42% of other women and 49% of men; 70% of all heterosexuals diagnosed were black Africans, born and infected in Africa. Of those, at least 40% were recent arrivals to the UK, and twice as many were diagnosed late as black-African heterosexuals infected in the UK. Short-term mortality was 3.2% (491/15 523); 6.1% among those diagnosed late and 0.7% among others (P < 0.01). Short-term mortality was lower among black-African compared with white heterosexuals (3.1 versus 4.5%; P < 0.01) because of diagnosis at a younger age. Earlier diagnosis would have reduced short-term mortality by 56% (249 fewer deaths) and all mortality by 32% between 2000 and 2004. CONCLUSION: Groups at high risk of late diagnosis should be targeted for health promotion activities, opportunistic screening, and removal of any barriers to testing. HIV testing in a variety of settings would reduce missed diagnoses and costs. New patient checks in primary care may provide the earliest opportunity to diagnose HIV infection among recent arrivals to the UK.

No time to wait: how many HIV-infected homosexual men are diagnosed late and consequently die? (England and Wales, 1993-2002).

OBJECTIVES: To present national trends of the estimated number and proportion of late HIV diagnoses and short-term mortality following diagnosis among men who have had sex with men (MSM). To determine separately risk factors for late diagnosis and short-term mortality. METHODS: Analysis of national HIV/AIDS case reports of new diagnoses linked to CD4 cell counts from the CD4 Surveillance Scheme. Inverse probability weighting adjusted for individuals with no CD4 cell count at diagnosis. Outcomes were late diagnosis (CD4 cell count <200 x 10(6) cells/l at diagnosis) and short-term mortality (death within 1 year of diagnosis). RESULTS: Of 14,158 new diagnoses, 31% were estimated as late diagnoses. Despite a decreasing trend (P trend <0.01) an estimated 430 (25%) MSM were still diagnosed late in 2001. Late diagnosis disproportionately affected individuals diagnosed outside London, of non-white ethnicity, and of older age. There were 710 (5.0% of 14 158) deaths within a year of HIV diagnosis. Estimated short-term mortality was 14% for MSM diagnosed late and 1% for other MSM (adjusted odds ratio, 10.8; 95% confidence interval, 7.7-15.9). Short-term mortality declined concurrently with availability of highly active antiretroviral therapy and was independently associated with age and diagnosis outside London but not ethnicity. CONCLUSIONS: The continued late diagnosis of one in four MSM means these individuals lose the option to start therapy early, miss opportunities to prevent further transmission and are approximately 10 times more likely to die within a year of diagnosis. Early diagnosis of all MSM in 2001 could have reduced short-term mortality by 84% and all mortality in that year by 22%.

WHO 'Treatment as Prevention' guidelines are unlikely to decrease HIV transmission in the UK unless undiagnosed HIV infections are reduced.

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.

Novel HIV-1 recombinants spreading across multiple risk groups in the United Kingdom: the identification and phylogeography of Circulating Recombinant Form (CRF) 50_A1D.

BACKGROUND: An increase in non-B HIV-1 infections among men who have sex with men (MSM) in the United Kingdom (UK) has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies. METHODS AND RESULTS: A total of 55,556 pol (reverse transcriptase and protease) sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL). Overall 72 patients shared the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug users (IDUs). In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints), which has been classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST). This estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a subtype B strain. CONCLUSIONS: We report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around 1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B. These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously distinct MSM and heterosexual epidemics.

Phylogenetic analyses reveal HIV-1 infections between men misclassified as heterosexual transmissions.

OBJECTIVE: HIV-1 subtype B infections are associated with MSM in the UK. Yet, around 13% of subtype B infections are found in those reporting heterosexual contact as transmission route. Using phylogenetics, we explored possible misclassification of sexual exposure among men diagnosed with HIV in the UK. DESIGN: Viral gene sequences linked to patient-derived information were used to identify phylogenetic transmission chains. METHODS: A total of 22,481 HIV-1 subtype B pol gene sequences sampled between 1996 and 2008 were analysed. Dated phylogenies were reconstructed and transmission clusters identified as clades of at least two sequences with a maximum genetic distance of 4.5%, a branch support of at least 95% and spanning 5 years. The characteristics of clusters containing at least one heterosexually acquired infection were analysed. RESULTS: Twenty-nine percent of the linked heterosexuals clustered exclusively with MSM. These were more likely to be men than women. Estimated misclassification of homosexually acquired infections ranged between 1 and 11% of the reported male heterosexuals diagnosed with HIV. Black African heterosexual men were more often phylogenetically linked to MSM than other ethnic group, with an estimated misclassification range between 1 and 21%. CONCLUSION: Overall, a small proportion of self-reported heterosexual men diagnosed with HIV could have been infected homosexually. However, up to one in five black African heterosexual men chose not to disclose sex with men at HIV diagnosis and preferred to be identified as heterosexual. Phylogenetic analyses can enhance surveillance-based risk information and inform national programmes for monitoring and preventing HIV infections.

HIV incidence in men who have sex with men in England and Wales 2001-10: a nationwide population study.

BACKGROUND: Control of HIV transmission could be achievable through an expansion of HIV testing of at-risk populations together with ready access and adherence to antiretroviral therapy. To examine whether increases in testing rates and antiretroviral therapy coverage correspond to the control of HIV transmission, we estimated HIV incidence in men who have sex with men (MSM) in England and Wales since 2001. METHODS: A CD4-staged back-calculation model of HIV incidence was used to disentangle the competing contributions of time-varying rates of diagnosis and HIV incidence to observed HIV diagnoses. Estimated trends in time to diagnosis, incidence, and undiagnosed infection in MSM were interpreted against a backdrop of increased HIV testing rates and antiretroviral-therapy coverage over the period 2001-10. FINDINGS: The observed 3·7 fold expansion in HIV testing in MSM was mirrored by a decline in the estimated mean time-to-diagnosis interval from 4·0 years (95% credible interval [CrI] 3·8-4·2) in 2001 to 3·2 years (2·6-3·8) by the end of 2010. However, neither HIV incidence (2300-2500 annual infections) nor the number of undiagnosed HIV infections (7370, 95% CrI 6990-7800, in 2001, and 7690, 5460-10 580, in 2010) changed throughout the decade, despite an increase in antiretroviral uptake from 69% in 2001 to 80% in 2010. INTERPRETATION: CD4 cell counts at HIV diagnosis are fundamental to the production of robust estimates of incidence based on HIV diagnosis data. Improved frequency and targeting of HIV testing, as well as the introduction of ART at higher CD4 counts than is currently recommended, could begin a decline in HIV transmission among MSM in England and Wales. FUNDING: UK Medical Research Council, UK Health Protection Agency.