End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain.

BACKGROUND: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. METHODS: End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. METHODS: Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: -6% to 54%). VE for those aged 18-64, who largely received cell-based vaccines, was 47% (95% CI: 37%-56%). Overall VE for 2-17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%-76%). CONCLUSION: The paper provides evidence of moderate influenza VE in 2022/23.

Interim 2023/2024 Season Influenza Vaccine Effectiveness in Primary and Secondary Care in the United Kingdom.

BACKGROUND: We report 2023/2024 season interim influenza vaccine effectiveness for three studies, namely, primary care in Great Britain, hospital settings in Scotland and hospital settings in England. METHODS: A test negative design was used to estimate vaccine effectiveness. RESULTS: Estimated vaccine effectiveness against all influenzas ranged from 63% (95% confidence interval 46 to 75%) to 65% (41 to 79%) among children aged 2-17, from 36% (20 to 49%) to 55% (43 to 65%) among adults 18-64 and from 40% (29 to 50%) to 55% (32 to 70%) among adults aged 65 and over. CONCLUSIONS: During a period of co-circulation of influenza A(H1N1)pdm09 and A(H3N2) in the United Kingdom, evidence for effectiveness of the influenza vaccine in both children and adults was found.

Risk of winter hospitalisation and death from acute respiratory infections in Scotland: national retrospective cohort study.

OBJECTIVES: We undertook a national analysis to characterise and identify risk factors for acute respiratory infections (ARIs) resulting in hospitalisation during the winter period in Scotland. DESIGN: A population-based retrospective cohort analysis. SETTING: Scotland. PARTICIPANTS: The study involved 5.4 million residents in Scotland. MAIN OUTCOME MEASURES: Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the association between risk factors and ARI hospitalisation. RESULTS: Between 1 September 2022 and 31 January 2023, there were 22,284 (10.9% of 203,549 with any emergency hospitalisation) ARI hospitalisations (1759 in children and 20,525 in adults) in Scotland. Compared with the reference group of children aged 6-17 years, the risk of ARI hospitalisation was higher in children aged 3-5 years (aHR = 4.55; 95% CI: 4.11-5.04). Compared with those aged 25-29 years, the risk of ARI hospitalisation was highest among the oldest adults aged ≥80 years (aHR = 7.86; 95% CI: 7.06-8.76). Adults from more deprived areas (most deprived vs. least deprived, aHR = 1.64; 95% CI: 1.57-1.72), with existing health conditions (≥5 vs. 0 health conditions, aHR = 4.84; 95% CI: 4.53-5.18) or with history of all-cause emergency admissions (≥6 vs. 0 previous emergency admissions, aHR = 7.53; 95% CI: 5.48-10.35) were at a higher risk of ARI hospitalisations. The risk increased by the number of existing health conditions and previous emergency admission. Similar associations were seen in children. CONCLUSIONS: Younger children, older adults, those from more deprived backgrounds and individuals with greater numbers of pre-existing conditions and previous emergency admission were at increased risk for winter hospitalisations for ARI.

Adeno-associated virus 2 infection in children with non-A-E hepatitis.

An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.

Epidemiology of SARS-CoV-2 during the first three waves in Scotland: a national record linkage study.

BACKGROUND: The early COVID-19 pandemic in Scotland-defined as the era before widespread access to vaccination and monoclonal antibody treatment-can be characterised into three distinct waves: March-July 2020, July 2020-April 2021 and May-August 2021. Each wave was met with various societal restrictions in an effort to reduce disease transmission and associated morbidity and mortality. Understanding the epidemiology of infections during these waves can provide valuable insights into future pandemic planning. METHODS: Scottish RT-PCR testing data reported up until 8 August 2021, the day prior to most restrictions being lifted in Scotland, were included. Demographic characteristics including age, sex and social deprivation associated with transmission, morbidity and mortality were compared across waves. A case-control analysis for each wave was then modelled to further compare risk factors associated with death over time. RESULTS: Of the 349 904 reported cases, there were 18 099, 197 251 and 134 554 in waves 1, 2 and 3, respectively. Hospitalisations, intensive care unit admissions and deaths appeared highest in wave 2, though risk factors associated with COVID-19 death remained similar across the waves. Higher deprivation and certain comorbidities were associated with higher deaths in all waves. CONCLUSIONS: Despite the higher number of cases reported in waves 2 and 3, case fatality rates were lower: likely a combination of improved detection of infections in younger age groups, introduction of social measures and vaccination. Higher social deprivation and comorbidities resulted in higher deaths for all waves.

Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022.

On 31 March 2022, Public Health Scotland was alerted to five children aged 3-5 years admitted to hospital with severe hepatitis of unknown aetiology. Retrospective investigation identified eight additional cases aged 10 years and younger since 1 January 2022. Two pairs of cases have epidemiological links. Common viral hepatitis causes were excluded in those with available results. Five children were adenovirus PCR-positive. Other childhood viruses, including SARS-CoV-2, have been isolated. Investigations are ongoing, with new cases still presenting.

Use of HIV Recency Assays for HIV Incidence Estimation and Other Surveillance Use Cases: Systematic Review.

BACKGROUND: HIV assays designed to detect recent infection, also known as "recency assays," are often used to estimate HIV incidence in a specific country, region, or subpopulation, alone or as part of recent infection testing algorithms (RITAs). Recently, many countries and organizations have become interested in using recency assays within case surveillance systems and routine HIV testing services to measure other indicators beyond incidence, generally referred to as "non-incidence surveillance use cases." OBJECTIVE: This review aims to identify published evidence that can be used to validate methodological approaches to recency-based incidence estimation and non-incidence use cases. The evidence identified through this review will be used in the forthcoming technical guidance by the World Health Organization (WHO) and United Nations Programme on HIV/AIDS (UNAIDS) on the use of HIV recency assays for identification of epidemic trends, whether for HIV incidence estimation or non-incidence indicators of recency. METHODS: To identify the best methodological and field implementation practices for the use of recency assays to estimate HIV incidence and trends in recent infections for specific populations or geographic areas, we conducted a systematic review of the literature to (1) understand the use of recency testing for surveillance in programmatic and laboratory settings, (2) review methodologies for implementing recency testing for both incidence estimation and non-incidence use cases, and (3) assess the field performance characteristics of commercially available recency assays. RESULTS: Among the 167 documents included in the final review, 91 (54.5%) focused on assay or algorithm performance or methodological descriptions, with high-quality evidence of accurate age- and sex-disaggregated HIV incidence estimation at national or regional levels in general population settings, but not at finer geographic levels for prevention prioritization. The remaining 76 (45.5%) described the field use of incidence assays including field-derived incidence (n=45), non-incidence (n=25), and both incidence and non-incidence use cases (n=6). The field use of incidence assays included integrating RITAs into routine surveillance and assisting with molecular genetic analyses, but evidence was generally weaker or only reported on what was done, without validation data or findings related to effectiveness of using non-incidence indicators calculated through the use of recency assays as a proxy for HIV incidence. CONCLUSIONS: HIV recency assays have been widely validated for estimating HIV incidence in age- and sex-specific populations at national and subnational regional levels; however, there is a lack of evidence validating the accuracy and effectiveness of using recency assays to identify epidemic trends in non-incidence surveillance use cases. More research is needed to validate the use of recency assays within HIV testing services, to ensure findings can be accurately interpreted to guide prioritization of public health programming.

Achieving consistency in measures of HIV-1 viral suppression across countries: derivation of an adjustment based on international antiretroviral treatment cohort data.

INTRODUCTION: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. METHODS: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. RESULTS: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56 ), with uncertainty range 85.5-90.6% (0.800.70 -0.800.44 ). CONCLUSIONS: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software.

Updates to Spectrum's case surveillance and vital registration tool for HIV estimates and projections.

INTRODUCTION: The Case Surveillance and Vital Registration (CSAVR) model within Spectrum estimates HIV incidence trends from surveillance data on numbers of new HIV diagnoses and HIV-related deaths. This article describes developments of the CSAVR tool to more flexibly model diagnosis rates over time, estimate incidence patterns by sex and age group and by key population group. METHODS: We modelled HIV diagnosis rate trends as a mixture of three factors, including temporal and opportunistic infection components. The tool was expanded to estimate incidence rate ratios by sex and age for countries with disaggregated reporting of new HIV diagnoses and AIDS deaths, and to account for information on key populations such as men who have sex with men (MSM), males who inject drugs (MWID), female sex workers (FSW) and females who inject drugs (FWID). We used a Bayesian framework to calibrate the tool in 71 high-income or low-HIV burden countries. RESULTS: Across countries, an estimated median 89% (interquartile range [IQR]: 78%-96%) of HIV-positive adults knew their status in 2019. Mean CD4 counts at diagnosis were stable over time, with a median of 456 cells/µl (IQR: 391-508) across countries in 2019. In European countries reporting new HIV diagnoses among key populations, median estimated proportions of males that are MSM and MWID was 1.3% (IQR: 0.9%-2.0%) and 0.56% (IQR: 0.51%-0.64%), respectively. The median estimated proportions of females that are FSW and FWID were 0.36% (IQR: 0.27%-0.45%) and 0.14 (IQR: 0.13%-0.15%), respectively. HIV incidence per 100 person-years increased among MSM, with median estimates reaching 0.43 (IQR: 0.29-1.73) in 2019, but remained stable in MWID, FSW and FWID, at around 0.12 (IQR: 0.04-1.9), 0.09 (IQR: 0.06-0.69) and 0.13% (IQR: 0.08%-0.91%) in 2019, respectively. Knowledge of HIV status among HIV-positive adults gradually increased since the early 1990s to exceed 75% in more than 75% of countries in 2019 among each key population. CONCLUSIONS: CSAVR offers an approach to using routine surveillance and vital registration data to estimate and project trends in both HIV incidence and knowledge of HIV status.

Contributions of the EURO 2020 football championship events to a third wave of SARS-CoV-2 in Scotland, 11 June to 7 July 2021.

Public Health Scotland used Scottish national contact tracing data to estimate the European football championship (EURO 2020) contributions to a third wave of SARS-CoV-2 infections. From 11 June to 7 July 2021, 2,632 (4%) of 63,874 SARS-CoV-2 cases self-reported attending a EURO 2020 event; 90% were male, of whom 73% were 20-39-year-olds. Most cases attended unofficial gatherings and averaged more contacts than the general population. Targeted guidance on celebrating safely in closed spaces is key.

Inferring population HIV incidence trends from surveillance data of recent HIV infection among HIV testing clients.

BACKGROUND: Measuring recent HIV infections from routine surveillance systems could allow timely and granular monitoring of HIV incidence patterns. We evaluated the relationship of two recent infection indicators with alternative denominators to true incidence patterns. METHODS: We used a mathematical model of HIV testing behaviours, calibrated to population-based surveys and HIV testing services programme data, to estimate the number of recent infections diagnosed annually from 2010 to 2019 in Côte d'Ivoire, Malawi, and Mozambique. We compared two different denominators to interpret recency data: those at risk of HIV acquisition (HIV-negative tests and recent infections) and all people testing HIV positive. Sex and age-specific longitudinal trends in both interpretations were then compared with modelled trends in HIV incidence, testing efforts and HIV positivity among HIV testing services clients. RESULTS: Over 2010-2019, the annual proportion of the eligible population tested increased in all countries, while positivity decreased. The proportion of recent infections among those at risk of HIV acquisition decreased, similar to declines in HIV incidence among adults (≥15 years old). Conversely, the proportion of recent infections among HIV-positive tests increased. The female-to-male ratio of the proportion testing recent among those at risk was closer to 1 than the true incidence sex ratio. CONCLUSION: The proportion of recent infections among those at risk of HIV acquisition is more indicative of HIV incidence than the proportion among HIV-positive tests. However, interpreting the observed patterns as surrogate measures for incidence patterns may still be confounded by different HIV testing rates between population groups or over time.

Trends in knowledge of HIV status and efficiency of HIV testing services in sub-Saharan Africa, 2000-20: a modelling study using survey and HIV testing programme data.

BACKGROUND: Monitoring knowledge of HIV status among people living with HIV is essential for an effective national HIV response. This study estimates progress and gaps in reaching the UNAIDS 2020 target of 90% knowledge of status, and the efficiency of HIV testing services in sub-Saharan Africa, where two thirds of all people living with HIV reside. METHODS: For this modelling study, we used data from 183 population-based surveys (including more than 2·7 million participants) and national HIV testing programme reports (315 country-years) from 40 countries in sub-Saharan Africa as inputs into a mathematical model to examine trends in knowledge of status among people living with HIV, median time from HIV infection to diagnosis, HIV testing positivity, and proportion of new diagnoses among all positive tests, adjusting for retesting. We included data from 2000 to 2019, and projected results to 2020. FINDINGS: Across sub-Saharan Africa, knowledge of status steadily increased from 5·7% (95% credible interval [CrI] 4·6-7·0) in 2000 to 84% (82-86) in 2020. 12 countries and one region, southern Africa, reached the 90% target. In 2020, knowledge of status was lower among men (79%, 95% CrI 76-81) than women (87%, 85-89) across sub-Saharan Africa. People living with HIV aged 15-24 years were the least likely to know their status (65%, 62-69), but the largest gap in terms of absolute numbers was among men aged 35-49 years, with 701 000 (95% CrI 611 000-788 000) remaining undiagnosed. As knowledge of status increased from 2000 to 2020, the median time to diagnosis decreased from 9·6 years (9·1-10) to 2·6 years (1·8-3·5), HIV testing positivity declined from 9·0% (7·7-10) to 2·8% (2·1-3·9), and the proportion of first-time diagnoses among all positive tests dropped from 89% (77-96) to 42% (30-55). INTERPRETATION: On the path towards the next UNAIDS target of 95% diagnostic coverage by 2025, and in a context of declining positivity and yield of first-time diagnoses, disparities in knowledge of status must be addressed. Increasing knowledge of status and treatment coverage among older men could be crucial to reducing HIV incidence among women in sub-Saharan Africa, and by extension, reducing mother-to-child transmission. FUNDING: Steinberg Fund for Interdisciplinary Global Health Research (McGill University); Canadian Institutes of Health Research; Bill & Melinda Gates Foundation; Fonds the recherche du Québec-Santé; UNAIDS; UK Medical Research Council; MRC Centre for Global Infectious Disease Analysis; UK Foreign, Commonwealth & Development Office.

Increasing Skin-to-Skin in a Level IV NICU: A Quality Improvement Project.

PURPOSE: To evaluate the effect of a bundled intervention on the number of skin-to-skin ("kangaroo care") events occurring in a level IV NICU. DESIGN: A quality improvement effort centering around the introduction of an intervention bundle intended to safely increase the rate of skin-to-skin holding. Rates of unplanned extubations were recorded as a balancing measure to estimate safety. SAMPLE: All infants admitted to the NICU from December 2017 through September 2019 were included. The "preintervention" period was the 6 months prior to the initiation of the intervention bundle (December 2017-May 2018). RESULTS: The absolute number of skin-to-skin holds increased from the preintervention phase (range 7-28 holds/month, median 11 holds/month) to the postintervention phase (range 16-100 holds/month, median 55 holds/month). The total unplanned extubations showed no significant change between the preintervention and postintervention periods.

Accuracy of self-reported HIV-testing history and awareness of HIV-positive status in four sub-Saharan African countries.

BACKGROUND: In many countries in sub-Saharan Africa, self-reported HIV testing history and awareness of HIV-positive status from household surveys are used to estimate the percentage of people living with HIV (PLHIV) who know their HIV status. Despite widespread use, there is limited empirical information on the sensitivity of those self-reports, which can be affected by nondisclosure. METHODS: Bayesian latent class models were used to estimate the sensitivity of self-reported HIV-testing history and awareness of HIV-positive status in four Population-based HIV Impact Assessment surveys in Eswatini, Malawi, Tanzania, and Zambia. Antiretroviral (ARV) metabolite biomarkers were used to identify persons on treatment who did not accurately report their status. For those without ARV biomarkers, we used a pooled estimate of nondisclosure among untreated persons that was 1.48 higher than those on treatment. RESULTS: Among PLHIV, the model-estimated sensitivity of self-reported HIV-testing history ranged from 96% to 99% across surveys. The model-estimated sensitivity of self-reported awareness of HIV status varied from 91% to 97%. Nondisclosure was generally higher among men and those aged 15-24 years. Adjustments for imperfect sensitivity did not substantially influence estimates of PLHIV ever tested (difference <4%) but the proportion of PLHIV aware of their HIV-positive status was higher than the unadjusted proportion (difference <8%). CONCLUSION: Self-reported HIV-testing histories in four Eastern and Southern African countries are generally robust although adjustment for nondisclosure increases estimated awareness of status. These findings can contribute to further refinements in methods for monitoring progress along the HIV testing and treatment cascade.

Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models.

BACKGROUND: The COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa. METHODS: In this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software [EMOD]) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population. FINDINGS: A 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39-1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023-420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected). INTERPRETATION: During the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence. FUNDING: Bill & Melinda Gates Foundation.

National HIV testing and diagnosis coverage in sub-Saharan Africa: a new modeling tool for estimating the 'first 90' from program and survey data

HIV testing services (HTS) are a crucial component of national HIV responses. Learning one's HIV diagnosis is the entry point to accessing life-saving antiretroviral treatment and care. Recognizing the critical role of HTS, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 90-90-90 targets stipulating that by 2020, 90% of people living with HIV know their status, 90% of those who know their status receive antiretroviral therapy, and 90% of those on treatment have a suppressed viral load. Countries will need to regularly monitor progress on these three indicators. Estimating the proportion of people living with HIV who know their status (i.e. the 'first 90'), however, is difficult. Methods: We developed a mathematical model (henceforth referred to as 'Shiny90') that formally synthesizes population-based survey and HTS program data to estimate HIV status awareness over time. The proposed model uses country-specific HIV epidemic parameters from the standard UNAIDS Spectrum model to produce outputs that are consistent with other national HIV estimates. Shiny90 provides estimates of HIV testing history, diagnosis rates, and knowledge of HIV status by age and sex. We validate Shiny90 using both in-sample comparisons and out-of-sample predictions using data from three countries: Côte d'Ivoire, Malawi, and Mozambique. Results: In-sample comparisons suggest that Shiny90 can accurately reproduce longitudinal sex-specific trends in HIV testing. Out-of-sample predictions of the fraction of people living with HIV ever tested over a 4-to-6-year time horizon are also in good agreement with empirical survey estimates. Importantly, out-of-sample predictions of HIV knowledge of status are consistent (i.e. within 4% points) with those of the fully calibrated model in the three countries when HTS program data are included. The model's predictions of knowledge of status are higher than available self-reported HIV awareness estimates, however, suggesting - in line with previous studies - that these self-reports could be affected by nondisclosure of HIV status awareness. Conclusion: Knowledge of HIV status is a key indicator to monitor progress, identify bottlenecks, and target HIV responses. Shiny90 can help countries track progress towards their 'first 90' by leveraging surveys of HIV testing behaviors and annual HTS program data.

Summarizing the results and methods of the 2019 Joint United Nations Programme on HIV/AIDS HIV estimates.

: UNAIDS and other partners provide support to countries to develop estimates of HIV and related indicators on an annual basis. These estimates are used to monitor epidemic trends, guide program planning and resource allocation, and inform policy decision-making. The collection of articles in this AIDS supplement provide the headline results for the 2019 UNAIDS estimates and describe the new developments in the methods used to produce these estimates.

National HIV testing and diagnosis coverage in sub-Saharan Africa: a new modeling tool for estimating the 'first 90' from program and survey data.

OBJECTIVE: HIV testing services (HTS) are a crucial component of national HIV responses. Learning one's HIV diagnosis is the entry point to accessing life-saving antiretroviral treatment and care. Recognizing the critical role of HTS, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 90-90-90 targets stipulating that by 2020, 90% of people living with HIV know their status, 90% of those who know their status receive antiretroviral therapy, and 90% of those on treatment have a suppressed viral load. Countries will need to regularly monitor progress on these three indicators. Estimating the proportion of people living with HIV who know their status (i.e. the 'first 90'), however, is difficult. METHODS: We developed a mathematical model (henceforth referred to as 'Shiny90') that formally synthesizes population-based survey and HTS program data to estimate HIV status awareness over time. The proposed model uses country-specific HIV epidemic parameters from the standard UNAIDS Spectrum model to produce outputs that are consistent with other national HIV estimates. Shiny90 provides estimates of HIV testing history, diagnosis rates, and knowledge of HIV status by age and sex. We validate Shiny90 using both in-sample comparisons and out-of-sample predictions using data from three countries: Côte d'Ivoire, Malawi, and Mozambique. RESULTS: In-sample comparisons suggest that Shiny90 can accurately reproduce longitudinal sex-specific trends in HIV testing. Out-of-sample predictions of the fraction of people living with HIV ever tested over a 4-to-6-year time horizon are also in good agreement with empirical survey estimates. Importantly, out-of-sample predictions of HIV knowledge of status are consistent (i.e. within 4% points) with those of the fully calibrated model in the three countries when HTS program data are included. The model's predictions of knowledge of status are higher than available self-reported HIV awareness estimates, however, suggesting - in line with previous studies - that these self-reports could be affected by nondisclosure of HIV status awareness. CONCLUSION: Knowledge of HIV status is a key indicator to monitor progress, identify bottlenecks, and target HIV responses. Shiny90 can help countries track progress towards their 'first 90' by leveraging surveys of HIV testing behaviors and annual HTS program data.

Global, regional and country-level 90-90-90 estimates for 2018: assessing progress towards the 2020 target.

BACKGROUND: In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and partners set the 90-90-90 target for the year 2020: diagnose 90% of all people living with HIV (PLHIV); treat 90% of people who know their status; and suppress the virus in 90% of people on treatment. In 2015, countries began reporting to UNAIDS on progress against 90-90-90 using standard definitions and methods. METHODS: We used data submitted to UNAIDS from 170 countries to assess country-specific progress towards 90-90-90 through 2018. To assess global and regional progress, overall and by sex for adults aged 15 years and older, we combined country-reported data with estimates generated with a Bayesian hierarchical model. RESULTS: A total of 60 countries reported on all three 90s in 2018, up from 23 in 2015. Among all PLHIV worldwide, 79% (67-92%) knew their HIV status. Of these, 78% (69-82%) were accessing treatment and 86% (72-92%) of people accessing treatment had suppressed viral loads. Of the 37.9 million (32.7-44.0 million) PLHIV worldwide, 53% (43-63%) had suppressed viral loads. The gap to fully achieving 73% of PLHIV with suppressed viral load was 7.7 million; 15 countries had already achieved this target by 2018. CONCLUSION: Increased data availability has led to improved measures of country and global progress towards the 90-90-90 target. Although gains in access to testing and treatment continue, many countries and regions are unlikely to reach the 90-90-90 target by 2020.

Estimating and projecting the number of new HIV diagnoses and incidence in Spectrum's case surveillance and vital registration tool.

OBJECTIVE: The Joint United Nations Programme on HIV/AIDS-supported Spectrum software package is used by most countries worldwide to monitor the HIV epidemic. In Spectrum, HIV incidence trends among adults (aged 15-49 years) are derived by either fitting to seroprevalence surveillance and survey data or generating curves consistent with case surveillance and vital registration data, such as historical trends in the number of newly diagnosed infections or AIDS-related deaths. This article describes development and application of the case surveillance and vital registration (CSAVR) tool for the 2019 estimate round. METHODS: Incidence in CSAVR is either estimated directly using single logistic, double logistic, or spline functions, or indirectly via the 'r-logistic' model, which represents the (log-transformed) per-capita transmission rate using a logistic function. The propensity to get diagnosed is assumed to be monotonic, following a Gamma cumulative distribution function and proportional to mortality as a function of time since infection. Model parameters are estimated from a combination of historical surveillance data on newly reported HIV cases, mean CD4 at HIV diagnosis and estimates of AIDS-related deaths from vital registration systems. Bayesian calibration is used to identify the best fitting incidence trend and uncertainty bounds. RESULTS: We used CSAVR to estimate HIV incidence, number of new diagnoses, mean CD4 at diagnosis and the proportion undiagnosed in 31 European, Latin American, Middle Eastern, and Asian-Pacific countries. The spline model appeared to provide the best fit in most countries (45%), followed by the r-logistic (25%), double logistic (25%), and single logistic models. The proportion of HIV-positive people who knew their status increased from about 0.31 [interquartile range (IQR): 0.10-0.45] in 1990 to about 0.77 (IQR: 0.50-0.89) in 2017. The mean CD4 at diagnosis appeared to be stable, at around 410 cells/µl (IQR: 224-567) in 1990 and 373 cells/µl (IQR: 174-475) by 2017. CONCLUSION: Robust case surveillance and vital registration data are routinely available in many middle-income and high-income countries while HIV seroprevalence surveillance and survey data may be scarce. In these countries, CSAVR offers a simpler, improved approach to estimating and projecting trends in both HIV incidence and knowledge of HIV status.