The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort.

BACKGROUND: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary "cyclical" cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. METHODS AND FINDINGS: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. CONCLUSIONS: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades.

The revolving door of HIV care: Revising the service delivery cascade to achieve the UNAIDS 95-95-95 goals.

Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes.

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.

Outcomes of patients lost to follow-up after antiretroviral therapy initiation in rural north-eastern South Africa.

OBJECTIVE: The vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa. METHODS: Using data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes. RESULTS: Between April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU. CONCLUSION: LTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low.

OBJECTIF: Le statut vital des patients perdus au suivi reste souvent inconnu dans les programmes de traitement antirétroviral (ART) en Afrique subsaharienne parce que les dossiers médicaux ne sont plus mis à jour une fois que le patient se désengage des soins. Notre objectif était d'évaluer les résultats des patients dans le nord-est de l'Afrique du Sud. MÉTHODES: A l'aide de données provenant d'une zone rurale du nord-est de l'Afrique du Sud, nous avons estimé l'incidence cumulée des résultats pour les patients (i) après le début du traitement à l'aide des dossiers cliniques et (ii) après la perte au suivi (PS) à l'aide des données des patients qui ont été reliées individuellement à la base de données du système de surveillance démographique et de santé (AHDSS) d'Agincourt. Outre les PS, nous avons pris en compte la mortalité, le réengagement et la migration hors du site de l'étude. La régression des risques proportionnels de Cox a été utilisée pour identifier les covariables de ces résultats pour le patient. RÉSULTATS: Entre avril 2014 et juillet 2017, 3.700 patients ont commencé l'ART constituant un suivi total de 6.818 années-personnes. Trois ans après le début de l'ART, les estimations des PS, de la mortalité et des transferts documentés selon les registres cliniques étaient de 41,0% (IC95%: 38,5% à 43,4%), 1,9% (IC95%: 1,0% à 3,2%) et 0,1% (IC95%: 0,0% -0,9%), respectivement. Parmi ceux qui étaient PS, l'incidence cumulative de réengagement, d'émigration et de mortalité à trois ans était de 38,1% (IC95%: 33,1% à 43,0%), 49,4% (IC95%: 43,1% à 55,3%) et 4,7% (IC95%: 3,5% -6,2%), respectivement. Les femmes enceintes ou allaitantes, les étrangers et les personnes qui ont commencé l'ART le plus récemment couraient un risque accru de PS. CONCLUSION: La PS chez les patients commençant une ART dans le nord-est de l'Afrique du Sud est relativement élevée et a augmenté ces dernières années à mesure que davantage de patients asymptomatiques ont commencé le traitement. Même si cette tendance est préoccupante à la lumière de la prévention de la transmission, nous avons également constaté que le réengagement dans les soins était courant et que la mortalité parmi les PS était relativement faible.

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

Background: Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. Methods: This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Results: Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/µL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Conclusions: Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

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.

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.

Can HIV recent infection surveillance help us better understand where primary prevention efforts should be targeted? Results of three pilots integrating a recent infection testing algorithm into routine programme activities in Kenya and Zimbabwe.

INTRODUCTION: Surveillance of recent HIV infections in national testing services has the potential to inform primary prevention programming activities. Focusing on procedures required to accurately determine recent infection, and the potential for recent infection surveillance to inform prevention efforts, we present the results of three independent but linked pilots of recency testing. METHODS: To distinguish recently acquired HIV infection from long-standing infection, in 2018 we applied a Recent Infection Testing Algorithm that combined a laboratory-based Limiting Antigen Avidity Enzyme Immunoassay with clinical information (viral-load; history of prior HIV diagnosis; antiretroviral therapy-exposure). We explored potential misclassification of test results and analysed the characteristics of participants with recent infection. We applied the algorithm in antenatal clinics providing prevention of mother-to-child transmission services in Siaya County, Kenya, outreach sites serving female sex workers in Zimbabwe, and routine HIV testing and counselling facilities in Nairobi, Kenya. In Nairobi, we also conducted recency testing among partners of HIV-positive participants. RESULTS: In Siaya County, 2.3% (10/426) of HIV-positive pregnant women were classified as recent. A risk factor analysis comparing women testing recent with those testing HIV-negative found women in their first trimester were significantly more likely to test recent than those in their second or third trimester. In Zimbabwe, 10.5% (33/313) of female sex workers testing HIV-positive through the outreach programme were classified recent. A risk factor analysis of women testing recent versus those testing HIV-negative, found no strong evidence of an association with recent infection. In Nairobi, among 532 HIV-positive women and men, 8.6% (46) were classified recent. Among partners of participants, almost a quarter of those who tested HIV-positive were classified as recent (23.8%; 5/21). In all three settings, the inclusion of clinical information helped improve the positive predictive value of recent infection testing by removing cases that were likely misclassified. CONCLUSIONS: We successfully identified recently acquired infections among persons testing HIV-positive in routine testing settings and highlight the importance of incorporating additional information to accurately classify recent infection. We identified a number of groups with a significantly higher proportion of recent infection, suggesting recent infection surveillance, when rolled-out nationally, may help in further targeting primary prevention efforts.

The association between being currently in school and HIV prevalence among young women in nine eastern and southern African countries.

INTRODUCTION: Interventions to keep adolescent girls and young women in school, or support their return to school, are hypothesised to also reduce HIV risk. Such interventions are included in the DREAMS combination package of evidence-based interventions. Although there is evidence of reduced risky sexual behaviours, the impact on HIV incidence is unclear. We used nationally representative surveys to investigate the association between being in school and HIV prevalence. METHODS: We analysed Demographic and Health Survey data from nine DREAMS countries in sub-Saharan Africa restricted to young women aged 15-19 (n = 20,429 in total). We used logistic regression to assess cross-sectional associations between being in school and HIV status and present odds ratios adjusted for age, socio-economic status, residence, marital status, educational attainment and birth history (aOR). We investigated whether associations seen differed across countries and by age. RESULTS: HIV prevalence (1.0%-9.8%), being currently in school (50.0%-72.6%) and the strength of association between the two, varied between countries. We found strong evidence that being currently in school was associated with a reduced odds of being HIV positive in Lesotho (aOR: 0.37; 95%CI: 0.17-0.79), Swaziland (aOR: 0.32; 95%CI: 0.17-0.59), and Uganda (aOR: 0.48: 95%CI: 0.29-0.80) and no statistically significant evidence for this in Kenya, Malawi, Mozambique, Tanzania, Zambia or Zimbabwe. CONCLUSIONS: Although the relationship is not uniform across countries or over time, these data are supportive of the hypothesis that young women in school are at lower risk of being HIV positive than those who leave school in some sub-Saharan African settings. There is a possibility of reverse causality, with pre-existing HIV infection leading to school drop-out. Further investigation of the contextual factors behind this variation will be important in interpreting the results of HIV prevention interventions promoting retention in school.

Population and antenatal-based HIV prevalence estimates in a high contracepting female population in rural South Africa.

BACKGROUND: To present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, we explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population. METHODS: HIV sero-prevalence amongst blood samples collected from women consenting to test during the 2005 annual longitudinal population-based serological survey was compared to anonymous unlinked HIV sero-prevalence amongst women attending antenatal care (ANC) first visits in six clinics (January to May 2005). Both surveillance systems were conducted as part of the Africa Centre Demographic Information System. RESULTS: Population-based HIV prevalence estimates for all women (25.2%) and pregnant women (23.7%) were significantly lower than that for ANC attendees (37.7%). A large proportion of women attending urban or peri-urban clinics would be predicted to be resident within rural areas. Although overall estimates remained significantly different, presenting and standardising estimates by age and location (clinic for ANC-based estimates and individual-residence for population-based estimates) made some group-specific estimates from the two surveillance systems more predictive of one another. CONCLUSION: It is likely that where ANC coverage and contraceptive use is widespread and fertility is low, population-based surveillance under-estimates HIV prevalence due to unrepresentative testing by age, residence and also probably by HIV status, and that ANC sentinel surveillance over-estimates prevalence due to selection bias in terms of age of sexual debut and contraceptive use. The results presented highlight the importance of accounting for unrepresentative testing, particularly by individual residence and age, through system design and statistical analyses.

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%.

Prevalent diagnosed HIV in England, Wales and Northern Ireland: adjusted totals 1996 to 2001 and extrapolations to 2004.

OBJECTIVE: To predict trends in diagnosed HIV prevalence by extrapolation to 2004 using data from the annual surveys of individuals receiving HIV-related care in England, Wales and Northern Ireland from 1996 to 2001. METHODS: Data from the annual surveys of prevalent HIV infections diagnosed (SOPHID) were adjusted for under-reporting and non-attendance and separately extrapolated for infections acquired homosexually, heterosexually and by other routes. The data were extrapolated using negative binomial and linear regression models based on the 1996 to 2001 annual surveys. RESULTS: The negative binomial model predicted an increase of 56% in diagnosed HIV prevalence in England, Wales and Northern Ireland between 2001 and 2004. The linear model predicted an increase of 25% for the same time period. The predicted increases are mostly driven by the large rise in the number of new diagnoses, in particular in individuals infected heterosexually. CONCLUSION: Increases in HIV prevalence in England, Wales and Northern Ireland have diverged from a linear trend. Negative binomial modelling of the data predicts that large rises in prevalence will continue during the early 2000s.

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.

A new method to assign country of HIV infection among heterosexuals born abroad and diagnosed with HIV.

OBJECTIVE: To apply a new method to ascertain likely place of HIV infection among persons born abroad and diagnosed with HIV in the United Kingdom (UK). DESIGN: Analyses of heterosexual adults born abroad, diagnosed with HIV in the UK between 2004 and 2010, and reported to the national HIV diagnoses database. METHODS: Year of infection was ascertained by applying an estimated rate of CD4 cell count decline between an individual's CD4 cell count at diagnosis and estimates of CD4-cell count at infection. A person was classified as having probably acquired HIV while living in the UK if estimated year of infection was later than reported year of arrival in the UK. RESULTS: Of 10 612 heterosexual adults born abroad included in the analyses, 85% (9065) were of black-African ethnicity. We estimate that 33% (26-39%) of persons acquired HIV while living in the UK. This percentage increased from 24% (16-39%) in 2004 to 46% (31-50%) in 2010 (P < 0.01). The estimate of 33% is three times higher than national estimates of HIV acquired in the UK based on clinic reports (11%) (P <  0.01). CONCLUSION: : Assigning place of HIV infection using routinely available clinical and demographic data and estimated rates of CD4 cell decline is feasible. We report a high and increasing proportion of persons born abroad who appear to have acquired their HIV infection while living in the UK. These findings highlight the need for continued targeted HIV prevention efforts, particularly among black-African communities.

Invasive pneumococcal disease among HIV-positive individuals, 2000-2009.

OBJECTIVES: To examine invasive pneumococcal disease (IPD) incidence, the impact of the 7-valent pneumococcal conjugate vaccines (PCV7s) programme on the distribution of Streptococcus pneumoniae serotypes and risk factors for IPD among HIV-positive adults. METHODS: We analysed adults (aged ≥15 years) reported to the HIV and IPD national datasets in England and Wales (2000-2009). Through data-linkage, changes in IPD incidence and serotype distribution were examined. Risk factors for IPD among HIV-positive adults were assessed using a case-control study. RESULTS: Among 63,109 HIV-positive adults, 951 were co-infected with IPD. The average annual incidence of IPD was 245 episodes per 100,000 HIV-positive adults and 246 of 100,000 among those aged 15-44 years. Incidence was higher among those not on antiretroviral therapy (ART) (281 of 100,000) and those with severe immunosuppression (563 of 100,000). Among 9283 adults aged 15-44 at IPD diagnosis, 2.4% were living with undiagnosed HIV. The proportion of IPD episodes in HIV-positive adults with serotypes covered by PCV7 was 23% in 2009, a 54% proportional reduction compared with pre-PCV7 (2000-2006); the reduction in adults of unknown HIV status was 70%. The proportion of IPD episodes among HIV-positive adults caused by serotypes covered by PCV13 was 61%. Significant risk factors for IPD in multivariate analysis included older aged (≥65 years), a lower nadir CD4 cell count and no previous ART. CONCLUSION: An HIV test should be offered and recommended to adults aged 15-44 years without other obvious IPD risk factors. Our study provides an evidence base to policy makers regarding the use of the new PCV13 in HIV-positive adults.

HIV transmission and high rates of late diagnoses among adults aged 50 years and over.

OBJECTIVES: Describe the epidemiology and impact of late diagnosis among older adults living with HIV and estimate age at infection. METHODS: Comparative national analyses between individuals diagnosed when aged 50 years and over with individuals diagnosed prior to 50 years. Age at infection was estimated using CD4 cell count at diagnosis. RESULTS: A total of 8255 older adults accessed HIV care in England, Wales and Northern Ireland in 2007, a 3.5-fold increase compared to 2000; with one in 10 individuals newly diagnosed in 2007. When compared with younger adults at diagnosis, older adults were significantly more likely to be men (74 vs. 58%; P < 0.001), infected through sex between men (40 vs. 34%; P < 0.001) and of white ethnicity (60 vs. 38%; P < 0.001). Older heterosexual adults were more likely to be infected within the UK (16 vs. 12%; P < 0.001), with evidence of travel abroad among white heterosexual men. Almost half (48%) of older adults were late presenters vs. a third (33%) of younger adults. Older late presenters were 14 times more likely to die within a year of diagnosis compared with older adults who were not diagnosed late (14 vs. 1%; P < 0.001) and had 2.4 times the risk of dying than younger late presenters. We estimate that nearly half (48%) of older adults diagnosed between 2000 and 2007 acquired their infection at age 50 and over. CONCLUSION: Our study provides evidence of HIV transmission, high rates of late presentation and an increased risk of short-term mortality among older adults. These findings highlight the need for increased targeted prevention efforts and strategies to increase HIV testing among older adults at risk of HIV.

Insights into the rise in HIV infections, 2001 to 2008: a Bayesian synthesis of prevalence evidence.

OBJECTIVE: To estimate trends in prevalence of HIV infection, undiagnosed and total, among adults aged 15-44 years in England and Wales since 2001. DESIGN: Multiple surveillance systems and survey data are available to inform different aspects of the HIV epidemic in England and Wales. To coherently and consistently combine this information to estimate trends in HIV prevalence, we apply a multiparameter evidence synthesis in a Bayesian statistical framework. METHODS: The study population is stratified by exposure group and region of residence. We synthesize data from behavioural and community surveys, unlinked anonymous seroprevalence surveys, and an annual survey of individuals with diagnosed HIV infection. Prevalence estimates are given with 95% credible intervals. RESULTS: The estimated number of prevalent HIV infections in 15-44-year-olds has increased from 32,400 (29,600-35,900) in 2001 to 54,500 (50,500-59,100) in 2008, corresponding to an estimated prevalence of 1.5 per 1000 (1.4-1.7) rising to 2.4 per 1000 (2.3-2.6) in 2008. A rise in prevalence of diagnosed infection contributes substantially to the increase. There is no evidence of a statistically significant decrease in the prevalence of undiagnosed infection. The proportion of infections that are diagnosed has therefore also increased. CONCLUSION: Although the increase in the proportion of infections that are diagnosed is encouraging, the rise in HIV prevalence and lack of evidence of a decrease in prevalence of undiagnosed infection suggest that diagnosis rates are not high enough to reduce the pool of individuals unaware of their infection and that new infections must be occurring.