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.

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.

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.

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.

How to achieve the global 90-90-90 target by 2020 in sub-Saharan Africa? A mathematical modelling study.

OBJECTIVES: The 90-90-90 target states that by 2020, 90% of people living with HIV should be diagnosed, 90% of those diagnosed treated, and 90% of those treated virally suppressed. We assessed the actions needed in each country of sub-Saharan Africa to achieve the 90-90-90 target. METHODS: We developed a mathematical model to assess the number of patients needing to start antiretroviral therapy (ART) between 2017 and 2020 to achieve 81% coverage by 2020 in each country, and the proportion of treated patients who are virally suppressed in four scenarios, combining two scenarios of retention (current-level or perfect), and routine viral load monitoring (current or universal coverage). We performed two separate simulations, one using observed failure rates from cohort studies, and one with considerably lower failure rates to set a theoretical lower limit. RESULTS: Our model projected that 2.9 million people started ART in 2017 in sub-Saharan Africa. If, depending on scenario, at least 2.2-2.7 million patients continue to start ART annually, 81% ART coverage will be reached in 2020 in sub-Saharan Africa on average. In 37% of the countries, a multiple-fold increase in annual number of patients starting ART is needed. Virological suppression >90% in 2020 could be reached only in the best-case scenario assuming low probability of treatment failure, elimination of treatment interruptions, and universal routine viral load monitoring. CONCLUSION: The 90-90-90 target is realistic in sub-Saharan Africa on average, but not necessarily in all individual countries. Each country should identify and focus on the specific gaps needing attention.

Monitoring HIV Treatment and the Health Sector Cascade: From Treatment Numbers to Impact.

Although not originally part of the MDGs, HIV treatment has been at the center of global HIV reporting since 2003, marked by achievement of the target of 15 million people receiving treatment before 2015 and 18.2 million (16.1-19.0 million) by mid 2016. Monitoring of treatment has been strengthened with harmonized partner reporting and accountability with regular, annual reports. Beyond treatment numbers, increasingly measures of treatment adherence, retention and outcomes have been reported though with varying quality and completeness. However, with the sustainable development goals (SDGs), monitoring treatment is changing in three important ways. First, treatment monitoring is shifting from numbers to coverage and gaps in a cascade of services to achieve universal access. Secondly, this requires greater emphasis on disaggregated, individual level patient and case monitoring systems, which can better support linkage, retention and chronic, long term care. Thirdly, the prevention, testing and treatment cascade with a clear results chain, links treatment numbers to impact, in terms of reduced viral load, mortality and incidence. This agenda will require a greater contribution of routine impact evaluation alongside monitoring, with treatment seen as part of a cascade of services to ensure impact on mortality and incidence. In conclusion, the shift from monitoring treatment numbers to treatment linked to universal access to prevention, testing and treatment and impact on mortality and incidence, will be critical to monitor, evaluate, and improve HIV programs as part of the SDGs.

The sexual health of male sex workers in England: analysis of cross-sectional data from genitourinary medicine clinics.

OBJECTIVES: Male sex workers (MSW) are thought to be at increased risk of sexually transmitted infections (STI), however, limited comparative data with other groups are available. Disparities among MSWs by migrant status may also exist. Using newly available, cross-sectional surveillance data, the characteristics of MSWs and other male genitourinary medicine (GUM) clinic attendees can be investigated. METHODS: Demographic characteristics, STI prevalence and service usage among MSWs and other male attendees between 1 January and 31 December 2011 were compared using logistic regression. RESULTS: In 2011, 627 780 men attended GUM clinics; 488 (0.08%) were identified as MSWs. MSWs used a variety of services, however, one in seven had no HIV test at presentation. Adjusting for demographic factors and self-reported sexual orientation, MSWs had increased risk of some STIs and reinfection compared to other male attendees (eg, ORadj of gonorrhoea infection: 2.21, 95% CI 1.61 to 3.01, p<0.001, 14.1% vs 4.8% reinfected in 2011, p=0.005). Service usage did not vary between migrant and UK-born MSWs, but migrant MSWs were twice as likely to be diagnosed with chlamydia. CONCLUSIONS: Some STIs are more prevalent and some reinfections more common among MSWs than other male attendees. A minority of MSWs do not appear to access STI/HIV testing through GUM clinics, and targeted interventions to improve uptake of testing in MSWs should be developed. Service usage and sexual health of MSWs does not appear to vary greatly by migrant status, though the increased risk of chlamydia infection among migrant MSWs should be investigated further.

The sexual health of female sex workers compared with other women in England: analysis of cross-sectional data from genitourinary medicine clinics.

BACKGROUND: While female sex workers (FSWs) are assumed to be at increased risk of sexually transmitted infections (STIs), there are limited comparative data with other population groups available. Using routine STI surveillance data, we investigated differences in sexual health between FSWs and other female attendees at genitourinary medicine (GUM) clinics in England. METHODS: Demographic characteristics, STI prevalence and service usage among FSWs and other attendees in 2011 were compared using logistic regression. RESULTS: In 2011, 2704 FSWs made 8411 recorded visits to 131/208 GUM clinics, (primarily large, FSW-specialist centres in London). FSWs used a variety of services, however, 10% did not have an STI/HIV test at presentation. By comparison with other female attendees, FSWs travelled further for their care and had increased risk of certain STIs (e.g., gonorrhoea ORadj: 2.76, 95% CI 2.16 to 3.54, p<0.001). Migrant FSWs had better sexual health outcomes than UK-born FSWs (e.g., period prevalence of chlamydia among those tested: 8.5% vs 13.5%, p<0.001) but were more likely to experience non-STI outcomes (eg, pelvic inflammatory disease ORadj: 2.92, 95% CI 1.57 to 5.41, p<0.001). CONCLUSIONS: FSWs in England have access to high-quality care through the GUM clinic network, but there is evidence of geographical inequality in access to these services. A minority do not appear to access STI/HIV testing through clinics, and some STIs are more prevalent among FSWs than other female attendees. Targeted interventions aimed at improving uptake of testing in FSWs should be developed, and need to be culturally sensitive to the needs of this predominantly migrant population.

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.

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.

Trends and associations of Trichomonas vaginalis infection in men and women with genital discharge syndromes in Johannesburg, South Africa.

OBJECTIVES: To better understand the epidemiology of Trichomonas vaginalis infection, we investigated the association between T vaginalis and demographic, clinical, microbiological and behavioural characteristics of patients presenting with genital discharges to a primary healthcare clinic in Johannesburg, South Africa. METHODS: During six annual surveys (2007-2012), 1218 cases of male urethral discharge syndrome and 1232 cases of vaginal discharge syndrome were consecutively recruited. Diagnostic methods included nucleic acid amplification (Neisseria gonorrhoeae, Chlamydia trachomatis, T vaginalis and Mycoplasma genitalium), microscopy (bacterial vaginosis and Candida) and serology (Treponema pallidum, herpes simplex virus type 2 (HSV-2) and HIV). Logistic regression analyses and χ2 tests were used to identify predictors of T vaginalis infection. RESULTS: The prevalence of T vaginalis decreased from 2007 to 2012 (men from 13.4% to 4.8%; women from 33.8 to 23.1%). Overall, 74 (6.1%) men and 291 (23.6%) women were T vaginalis positive, with the highest prevalence in those aged ≥40 years (men 13.6%; women 30.9%). T vaginalis infection occurred more often in pregnant women (adjusted OR (aOR) 2.67; 95% CI 1.29 to 5.54) and in women with serological evidence of T pallidum (aOR 1.63; 95% CI 1.08 to 2.45) or HSV-2 infections (aOR 1.75; 95% CI 1.16 to 2.64). T vaginalis infection occurred less often in men with coexistent gonorrhoea (aOR 0.35; 95% CI 0.21 to 0.57) and in women with either bacterial vaginosis (aOR 0.60; 95% CI 0.44 to 0.82) or Candida morphotypes (OR 0.61; 95% CI 0.43 to 0.86). CONCLUSIONS: Although the prevalence of T vaginalis infection has decreased over time, it remains an important cause of genital discharge in South Africa, particularly in older patients and pregnant women.

Trends in HIV prevalence among young people in generalised epidemics: implications for monitoring the HIV epidemic.

BACKGROUND: Countries measure trends in HIV incidence to assess the impact of HIV prevention and treatment programmes. Most countries have approximated trends in HIV incidence through modelled estimates or through trends in HIV prevalence among young people (aged 15-24 years) assuming they have recently become sexually active and have thus only been recently exposed to HIV. METHODS: Trends in HIV incidence are described and results are compared using three proxy measures of incidence: HIV prevalence among young women attending antenatal clinics (ANCs) in 22 countries; HIV prevalence among young male and female nationally representative household survey respondents in 14 countries; and modelled estimates of adult (ages 15-49 years) HIV incidence in 26 countries. The significance of changes in prevalence among ANC attendees and young survey respondents is tested. RESULTS: Among 26 countries, 25 had evidence of some decline in HIV incidence and 15 showed statistically significant declines in either ANC data or survey data. Only in Mozambique did the direction of the trend in young ANC attendees differ from modelled adult incidence, and in Mali and Zambia trends among young men differed from trends in adult incidence. The magnitude of change differed by method. CONCLUSIONS: Trends in HIV prevalence among young people show encouraging declines. Changes in fertility patterns, HIV-infected children surviving to adulthood, and participation bias could affect future proxy measures of incidence trends.

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.

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.

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.

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.

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.

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.

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.