Appraising the HIV Prevention Cascade methodology to improve HIV prevention targets: Lessons learned from a general population pilot study in east Zimbabwe.

Introduction: Multiple HIV Prevention Cascades (HPC) formulations have been proposed to assist advocacy, monitoring of progress of HIV prevention implementation and research to identify ways to increase use of HIV prevention methods. Schaefer and colleagues proposed a unifying formulation suitable for widespread use across different populations which could be used for routine monitoring or advocacy. Robust methods for defining and interpreting this HPC formulation using real world data is required. Methods: Data collected as part of the Manicaland Pilot HIV Prevention Cascades Study, east Zimbabwe, in 2018-19, was used to validate the HPC framework for PrEP, VMMC, male condom and combination prevention method use. Validation measures included feasibility of populating the HPC, contrasting simple vs complex measures of the HPC (using 2-sample proportion test), and testing ability of main bars to predict prevention use and testing whether sub-bars explained why people were lost from the HPC using logistic regression. Results: It was possible to populate the HPC for both individual and combined prevention methods using pilot survey data. Most steps were associated with prevention method usage outcomes, except for VMMC. There were significant overlaps between individuals reporting positive responses for the main bar and those citing barriers to motivation. To refine the HPC's access bar definition, it is suggested to also consider individuals who report access barriers. While the HPC framework identifies barriers to individual prevention methods, challenges arise in identifying those for combined prevention. Discussion: Our study successfully utilised questionnaires from the Manicaland HPC pilot survey to measure the HPC for individual and combined prevention methods. This demonstrates the feasibility of populating this framework using general population survey data and designated questionnaire modules. We propose a final formulation of the HPC, questionnaire modules and methods to create it. With proper evaluation and promotion, the HPC can enhance prevention services, aiding in the crucial reduction of HIV incidence.

Dynamic HIV risk differentiation among youth: Validation of a tool for prioritization of prevention in East Zimbabwe.

Background: Differentiating risk for HIV infection is important for providing focussed prevention options to individuals. We conducted a longitudinal study to validate a risk-differentiation tool for predicting HIV or HSV-2 acquisition among HIV-negative youth. Setting: Population-based household survey in east Zimbabwe. Methods: HIV and HSV-2 status and HIV behavioural risk factors were assessed in two surveys conducted 12 months apart among young people. Associations between risk-behaviours and combined HIV/HSV-2 incident infection were estimated using proportional hazards models. We calculated the sensitivity and specificity of risk-differentiation questions in predicting HIV/HSV-2 acquisition and quantified changes between surveys among low, medium, and high-risk categories. Results: In total, 44 HIV/HSV-2 seroconversions were observed in 1812 person-years of follow up (2.43/100PY, 95%CI: 1.71-3.15); 50% of incident cases reported never having had sex at baseline. Risk of HIV/HSV-2 acquisition was higher for those reporting non-regular partners (women: HR=2.71, 95% CI:1.12-6.54, men: HR=1.37, 95%CI: 0.29-6.38) and those reporting having a partner with a sexually transmitted infection (STI) (HR=7.62 (1.22-47.51). Adding a question on non-regular partnerships increased tool sensitivity from 18.2% to 38.6%, and further to 77.3% when restricted to those who had ever had sex. Individual risk category increased for 28% of men and 17% of women over 12-months. Conclusion: The refined risk differentiation tool identified a high proportion of youth at risk of HIV acquisition. Despite this, half of incident infections were among individuals who reported no prior sexual activity. The shifting patterns of risk behaviours underscore the need for dynamic prevention engagement strategies in high HIV prevalence or incidence settings.

Guidance for triangulating data and estimates of HIV prevalence among pregnant women and coverage of PMTCT using the Spectrum AIDS Impact Module.

BACKGROUND: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Non-representative programme data may lead to inaccurate estimates HIV prevalence and treatment coverage for pregnant women. SETTING: 154 countries and subnational locations across 126 countries. METHODS: Using 2023 UNAIDS HIV estimates, we calculated three ratios: (1) HIV prevalence among pregnant women to all women 15-49y (prevalence), (2) ART coverage before pregnancy to women 15-49y ART coverage (ART pre-pregnancy), and (3) ART coverage at delivery to women 15-49y ART coverage (PMTCT coverage). We developed an algorithm to identify and adjust inconsistent results within regional ranges in Spectrum-AIM, illustrated using Burkina Faso's estimates. RESULTS: In 2022, the mean regional ratio of prevalence among pregnant women to all women ranged from 0.68 to 0.95. ART coverage pre-pregnancy ranged by region from 0.40 to 1.22 times ART coverage among all women. Mean regional PMTCT coverage ratios ranged from 0.85 to 1.51. The prevalence ratio in Burkina Faso was 1.59, above the typical range 0.62-1.04 in western and central Africa. Antenatal clinics reported more PMTCT recipients than estimated HIV-positive pregnant women from 2015 to 2019. We adjusted inputted PMTCT programme data to enable consistency of HIV prevalence among pregnant women from programmatic routine HIV testing at antenatal clinics with values typical for Western and central Africa. CONCLUSION: These ratios offer Spectrum-AIM users a tool to gauge the consistency of their HIV prevalence and treatment coverage estimates among pregnant women with other countries in the region.

Population size, HIV prevalence, and antiretroviral therapy coverage among key populations in sub-Saharan Africa: collation and synthesis of survey data, 2010-23.

BACKGROUND: Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa. METHODS: Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors. FINDINGS: We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV. INTERPRETATION: Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates. FUNDING: UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health.

HIV incidence among women engaging in sex work in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: Women who engage in sex work in sub-Saharan Africa have a high risk of acquiring HIV infection. HIV incidence has declined among all women in sub-Saharan Africa, but trends among women who engage in sex work are poorly characterised. We synthesised data on HIV incidence among women who engage in sex work in sub-Saharan Africa and compared these with the total female population to understand relative incidence and trends over time. METHODS: We searched MEDLINE, Embase, Global Health, and Google Scholar from Jan 1, 1990, to Feb 28, 2024, and grey literature for studies that reported empirical estimates of HIV incidence among women who engage in sex work in any sub-Saharan Africa country. We calculated incidence rate ratios (IRRs) compared with total female population incidence estimates matched for age, district, and year, did a meta-analysis of IRRs, and used a continuous mixed-effects model to estimate changes in IRR over time. FINDINGS: From 32 studies done between 1985 and 2020, 2194 new HIV infections were observed among women who engage in sex work over 51 490 person-years. Median HIV incidence was 4·3 per 100 person years (IQR 2·8-7·0 per 100 person-years). Incidence among women who engage in sex work was eight times higher than matched total population women (IRR 7·8 [95% CI 5·1-11·8]), with larger relative difference in western and central Africa (19·9 [9·6-41·0]) than in eastern and southern Africa (4·9 [3·4-7·1]). There was no evidence that IRRs changed over time (IRR per 5 years: 0·9 [0·7-1·2]). INTERPRETATION: Across sub-Saharan Africa, HIV incidence among women who engage in sex work remains disproportionately high compared with the total female population. However, constant relative incidence over time indicates HIV incidence among women who engage in sex work has declined at a similar rate. Location-specific data for women who engage in sex work incidence are sparse, but improved surveillance and standardisation of incidence measurement approaches could fill these gaps. Sustained and enhanced HIV prevention for women who engage in sex work is crucial to address continuing inequalities and ensure declines in new HIV infections. FUNDING: Bill & Melinda Gates Foundation, UK Research and Innovation, National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

The contribution of intimate partner violence to vertical HIV transmission: a modelling analysis of 46 African countries.

BACKGROUND: Addressing gender inequities could be key to the elimination of vertical transmission of HIV. Women experiencing intimate partner violence (IPV) might be at an increased risk of vertical transmission due to their vulnerability to HIV acquisition and barriers to access to and retention in care. Sub-Saharan Africa, where IPV burden is among the highest globally, accounts for most new paediatric HIV infections. We aimed to examine the proportion of excess vertical transmission attributable to IPV in this region. METHODS: In this modelling analysis, we created a probability tree model of vertical HIV transmission among women aged 15-49 years in 46 African countries. We estimated the proportion of vertical transmission attributable to past-year physical or sexual IPV, or both, as an age-standardised population attributable fraction (PAF) and as excess vertical transmission risk per 1000 births among women experiencing IPV. We incorporated perinatal and postnatal vertical transmission among women who acquired HIV before pregnancy, during pregnancy, and during breastfeeding. Fertility, HIV prevalence, HIV incidence, antiretroviral therapy (ART) uptake, and ART retention varied in the model by women's IPV experience. The model was parameterised using UNAIDS' 2023 Spectrum model data, WHO's Global Database on Violence Against Women, and the peer-reviewed literature. Uncertainty intervals (95% UI) were calculated through 1000 Monte Carlo simulations. FINDINGS: Across 46 countries 13% (95% UI 6-21) of paediatric HIV infections in 2022 were attributed to IPV, corresponding to over 22 000 paediatric infections. The PAF ranged from 4% (2-7) in Niger to 28% (13-43) in Uganda. The PAF was highest among girls aged 15-19 years (20%, 8-33) and lowest among women aged 45-49 years (6%, 3-9). In southern Africa, where women's HIV prevalence is highest (23%), IPV led to 11 (5-20) additional infections per 1000 births among women affected by IPV. INTERPRETATION: IPV might be responsible for one in eight paediatric HIV infections in sub-Saharan Africa. Ending IPV could accelerate vertical transmission elimination, especially among young women who bear the highest burden of violence. FUNDING: Canadian Institutes of Health Research, Canada Research Chair, and Fonds de recherche du Québec-Santé. TRANSLATIONS: For the French, Georgian and Spanish translations of the abstract see Supplementary Materials section.

Guidance for triangulating data and estimates of HIV prevalence among pregnant women and coverage of PMTCT using the Spectrum AIDS Impact Module.

Background: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Non-representative programme data may lead to inaccurate estimates HIV prevalence and treatment coverage for pregnant women. Setting: 154 locations in 126 countries. Methods: Using 2023 UNAIDS HIV estimates, we calculated three ratios: (1) HIV prevalence among pregnant women to all women 15-49y (prevalence), (2) ART coverage before pregnancy to women 15-49y ART coverage (ART pre-pregnancy), and (3) ART coverage at delivery to women 15-49y ART coverage (PMTCT coverage). We developed an algorithm to identify and adjust inconsistent results within regional ranges in Spectrum-AIM, illustrated using Burkina Faso's estimates. Results: In 2022, the mean regional ratio of prevalence among pregnant women to all women ranged from 0.68 to 0.95. ART coverage pre-pregnancy ranged by region from 0.40 to 1.22 times ART coverage among all women. Mean regional PMTCT coverage ratios ranged from 0.85 to 1.51. The prevalence ratio in Burkina Faso was 1.59, above the typical range 0.62-1.04 in western and central Africa. Antenatal clinics reported more PMTCT recipients than estimated HIV-positive pregnant women from 2015 to 2019. We adjusted inputted PMTCT programme data to enable consistency of HIV prevalence among pregnant women from programmatic routine HIV testing at antenatal clinics with values typical for Western and central Africa. Conclusion: These ratios offer Spectrum-AIM users a tool to gauge the consistency of their HIV prevalence and treatment coverage estimates among pregnant women with other countries in the region.

Association Between Early Sexual Debut and New HIV Infections Among Adolescents and Young Adults in 11 African Countries.

We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10-24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: A systematic review and meta-regression.

BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.

Cost-effectiveness of 4CMenB vaccination against gonorrhea: importance of dosing schedule, vaccine sentiment, targeting strategy, and duration of protection.

BACKGROUND: Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination. METHODS: Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection. RESULTS: Vaccination with one or two primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering "Vaccination-according-to-Risk" (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more-restrictive strategy of "Vaccination-on-Diagnosis" (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR(2-dose) saves £7.62M(95%CrI:1.15-17.52) and gains 81.41(28.67-164.23) QALYs over 10 years; VoD(2-dose) saves £3.40M(0.48-7.71) and gains 41.26(17.52-78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by ∼30%(VoD) or ∼60%(VaR). CONCLUSIONS: At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.

Future HIV epidemic trajectories in South Africa and projected long-term consequences of reductions in general population HIV testing: a mathematical modelling study.

BACKGROUND: After successful intensive interventions to rapidly increase HIV awareness, coverage of antiretroviral therapy (ART), and viral suppression, HIV programmes in eastern and southern Africa are considering scaling back of some interventions, such as widespread general population HIV testing. We aimed to model whether scaling back of general population HIV testing in South Africa could result in a resurgence of the HIV epidemic or substantial slowing of declines in HIV incidence, resulting in increased long-term ART. METHODS: In this modelling study, we used the Thembisa 4.5 model (a deterministic compartmental model of HIV transmission in South Africa) to project the South African HIV epidemic to 2100 assuming the continuation of 2022 epidemiological conditions and HIV programme implementation. We assessed how implementing reductions in general population HIV testing services in 2025 (while maintaining antenatal, symptom-based, and risk-based testing modalities and other HIV prevention services at 2022 levels) would affect HIV incidence and prevalence among people aged 15-49 years, the year in which incidence would reach one per 1000 people aged 15-49 years (the threshold for virtual elimination of HIV), and associated costs, as well as numbers of additional new HIV infections and AIDS-related deaths. We also modelled the effects of delaying reductions in general population testing services by 5-year increments. Additionally, we modelled the potential effects of reductions in general population testing services in combination with increases or decreases in ART interruption rates (ie, the annual rate at which people who are on ART discontinue ART) and condom usage in 2025-35. FINDINGS: If general population HIV testing services and the HIV risk environment of 2022 were maintained, we projected that HIV incidence would steadily decline from 4·95 (95% CI 4·40-5·34) per 1000 population in 2025 to 0·14 (0·05-0·31) per 1000 in 2100, and that the so-called virtual elimination threshold of less than one new infection per 1000 population per year would be reached in 2055 (95% CI 2051-2060). Scaling back of general population HIV testing services by 25%, 50%, or 75% in 2025 delayed time to reaching the virtual elimination threshold by 5, 13, or 35 years, respectively, whereas complete cessation of general population testing would result in the threshold not being attained by 2100. Although the incidence of HIV continued to fall when general HIV testing services were reduced, our modelling suggested that, with reductions of between 25% and 100%, between 396 000 (95% CI 299 000-474 000) and 2·50 million (1·97 million-2·98 million) additional HIV infections and between 115 000 (94 000-135 000) and 795 000 (670 000-926 000) additional AIDS-related deaths would occur between 2025 and 2075, depending on the extent of reduction in testing. Delaying reductions in general population HIV testing services for 5-25 years mitigated some of these effects. HIV testing accounted for only 5% of total programmatic costs at baseline; reducing testing moderately reduced short-term total annual costs, but increased annual costs after 25 years. Increases in ART interruption and reductions in condom usage were projected to slow the decline in incidence and increase the coverage of general HIV testing services required to control transmission but did not cause rapid resurgence in HIV infections. INTERPRETATION: Our modelling suggests that scaling back of general population HIV testing would not result in a resurgence of HIV infections, but would delay attainment of incidence-reduction targets and result in long-term increases in HIV infections, AIDS-related deaths, and costs (via increased need for ART provision). HIV programmes need to balance short-term potential resource savings with long-term epidemic control objectives. FUNDING: Bill & Melinda Gates Foundation.

Dynamic models augmented by hierarchical data: an application of estimating HIV epidemics at sub-national level.

Dynamic models have been successfully used in producing estimates of HIV epidemics at the national level due to their epidemiological nature and their ability to estimate prevalence, incidence, and mortality rates simultaneously. Recently, HIV interventions and policies have required more information at sub-national levels to support local planning, decision-making and resource allocation. Unfortunately, many areas lack sufficient data for deriving stable and reliable results, and this is a critical technical barrier to more stratified estimates. One solution is to borrow information from other areas within the same country. However, directly assuming hierarchical structures within the HIV dynamic models is complicated and computationally time-consuming. In this article, we propose a simple and innovative way to incorporate hierarchical information into the dynamical systems by using auxiliary data. The proposed method efficiently uses information from multiple areas within each country without increasing the computational burden. As a result, the new model improves predictive ability and uncertainty assessment.

Burden and Trends of Symptomatic Sexually Transmitted Infections in Malawi From 2000 to 2021: Comparative Analysis of Survey and Case Report Data.

BACKGROUND: In settings without etiologic testing for sexually transmitted infections (STIs), programs rely on STI symptom data to inform priorities. To evaluate whether self-reported STI symptoms in household surveys consistently represent the STI burden, we compared symptomatic infection rates between survey self-reporting and health facility case reporting in Malawi. METHODS: We analyzed self-reported symptoms and treatment seeking in the past year among sexually active adults from 4 Malawi Demographic and Health Surveys between 2000 and 2015. Bayesian mixed-effects models were used to estimate temporal trends, spatial variation, and sociodemographic determinants. Survey reporting was compared with health facility syndromic diagnoses between 2014 and 2021. RESULTS: In surveys, 11.0% (95% confidence interval, 10.7%-11.4%) of adults reported STI or STI-related symptoms in the last year, of whom 54.2% (52.8%-55.7%) sought treatment. In facilities, the mean annual symptomatic case diagnosis rate was 3.3%. Survey-reported treatment in the last year was 3.8% (95% credible interval, 2.3%-6.1%) for genital ulcer, 3.8% (2.0%-6.7%) for vaginal discharge, and 2.6% (1.2%-4.7%) for urethral discharge. Mean annual diagnosis rates at facilities were 0.5% for genital ulcer, 2.2% for vaginal discharge, and 2.0% for urethral discharge. Both data sources indicated a higher burden of symptoms among women, individuals older than 25 years, and those in Southern Malawi. CONCLUSIONS: Survey and facility case reports indicated similar spatial and demographic patterns of STI symptom burden and care seeking, but implied large differences in the magnitude and relative burden of symptoms, particularly genital ulcer, which could affect program priorities. Targeted etiologic surveillance would improve interpretation of these data to enable more comprehensive STI surveillance.

Substantial but spatially heterogeneous progress in male circumcision for HIV prevention in South Africa.

BACKGROUND: Voluntary medical male circumcision (VMMC) reduces the risk of male HIV acquisition by 60%. Programmes to provide VMMCs for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Traditional circumcision is also a long-standing male coming-of-age ritual, but practices vary considerably across populations. Accurate estimates of circumcision coverage by age, type, and time at subnational levels are required for planning and delivering VMMCs to meet targets and evaluating their impacts on HIV incidence. METHODS: We developed a Bayesian competing risks time-to-event model to produce region-age-time-type specific probabilities and coverage of male circumcision with probabilistic uncertainty. The model jointly synthesises data from household surveys and health system data on the number of VMMCs conducted. We demonstrated the model using data from five household surveys and VMMC programme data to produce estimates of circumcision coverage for 52 districts in South Africa between 2008 and 2019. RESULTS: Nationally, in 2008, 24.1% (95% CI: 23.4-24.8%) of men aged 15-49 were traditionally circumcised and 19.4% (18.9-20.0%) were medically circumcised. Between 2010 and 2019, 4.25 million VMMCs were conducted. Circumcision coverage among men aged 15-49 increased to 64.0% (63.2-64.9%) and medical circumcision coverage to 42% (41.3-43.0%). Circumcision coverage varied widely across districts, ranging from 13.4 to 86.3%. The average age of traditional circumcision ranged between 13 and 19 years, depending on local cultural practices. CONCLUSION: South Africa has made substantial, but heterogeneous, progress towards increasing medical circumcision coverage. Detailed subnational information on coverage and practices can guide programmes to identify unmet need to achieve national and international targets.

Voluntary medical male circumcision reduces the risk of male HIV acquisition. Programmes to provide circumcisions for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Estimates of circumcision coverage are needed for planning and delivering circumcisions to meet targets and evaluate their impacts on HIV incidence. We developed a model to integrate date from both household surveys and health systems on the number of circumcisions conducted, and applied it to understand how the practices and coverage of circumcision are changing in South Africa. National circumcision coverage increased considerably between 2008 and 2019, however, there remains a substantial subnational variation across districts and age groups. Further progress is needed to reach national and international targets.

Measuring HIV Acquisitions Among Partners of Key Populations: Estimates From HIV Transmission Dynamic Models.

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models. SETTING: One hundred seventy-eight settings (106 countries). METHODS: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020. RESULTS: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29). CONCLUSIONS: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.

Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa.

BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

Updated Data and Methods for the 2023 UNAIDS HIV Estimates.

ABSTRACT: Each year, supported by the Joint United Nations Programme on HIV/AIDS (UNAIDS), country teams across the globe produce estimates that chart the state of their HIV epidemics. In 2023, HIV estimates were available for 174 countries, accounting for 99% of the global population, of which teams from 150 countries actively engaged in this process. The methods used to derive these estimates are developed under the guidance of the UNAIDS Reference Group on Estimates, Modeling, and Projections (www.epidem.org). Updates to these methods and epidemiological analyses that inform parameters and assumptions are documented in this supplement.

Improved Indicators for Subnational Unmet Antiretroviral Therapy Need in the Health System: Updates to the Naomi Model in 2023.

BACKGROUND: Quantifying subnational need for antiretroviral therapy (ART) for HIV is challenging because people living with HIV (PLHIV) access health facilities in areas that may differ from their residence. We defined and demonstrated new indicators for PLHIV treatment needed to guide health system target setting and resource allocation. SETTING: Botswana. METHODS: We extended Naomi, a Bayesian small-area model for estimating district-level HIV indicators from national household survey and HIV service delivery data. We used model outputs for ART seeking probabilities in neighboring districts to define the "PLHIV (attending)" indicator representing the estimated number of PLHIV who would seek treatment at health facilities in a district, and "Untreated PLHIV attending" representing gaps in ART service provision. Botswana 2021 district HIV estimates were used to demonstrate new outputs and assess the sensitivity to uncertainty in district population sizes. RESULTS: Across districts of Botswana, estimated adult ART coverage in December 2021 ranged 90%-96%. In the capital city Gaborone, there were 50,400 resident PLHIV and 64,200 receiving ART, of whom 24% (95% CI: 20 to 32) were estimated to reside in neighboring districts. Applying ART attendance probabilities gave a "PLHIV attending" denominator of 68,300 and unmet treatment need of 4100 adults (95% CI: 3000 to 5500) for Gaborone health facilities. The facility-based "PLHIV attending" denominator was less-sensitive to fluctuations in district population size assumptions. CONCLUSIONS: New indicators provided more consistent targets for HIV service provision, but are limited by ART data quality. This challenge will increase as treatment coverage reaches high levels and treatment gaps are smaller.

Triangulation of Routine Antenatal HIV Prevalence Data and Adjusted HIV Estimates in Mozambique.

BACKGROUND: Routine health system data are central to monitoring HIV trends. In Mozambique, the reported number of women receiving antenatal care (ANC) and antiretroviral therapy for prevention of mother-to-child transmission (PMTCT) has exceeded the Spectrum-estimated number of pregnant women since 2017. In some provinces, reported HIV prevalence in pregnant women has declined faster than epidemiologically plausible. We hypothesized that these issues are linked and caused by programmatic overenumeration of HIV-negative pregnant women at ANC. METHODS: We triangulated program-reported ANC client numbers with survey-based fertility estimates and facility birth data adjusted for the proportion of facility births. We used survey-reported ANC attendance to produce adjusted time series of HIV prevalence in pregnant women, adjusted for hypothesized program double counting. We calibrated the Spectrum HIV estimation models to adjusted HIV prevalence data to produce adjusted adult and pediatric HIV estimates. RESULTS: ANC client numbers were not consistent with facility birth data or modeled population estimates indicating ANC data quality issues in all provinces. Adjusted provincial ANC HIV prevalence in 2021 was median 45% [interquartile range 35%-52% or 2.3 percentage points (interquartile range 2.5-3.5)] higher than reported HIV prevalence. In 2021, calibrating to adjusted antenatal HIV prevalence lowered PMTCT coverage to less than 100% in most provinces and increased the modeled number of new child infections by 35%. The adjusted results better reconciled adult and pediatric antiretroviral treatment coverage and antenatal HIV prevalence with regional fertility estimates. CONCLUSIONS: Adjusting HIV prevalence in pregnant women using nationally representative household survey data on ANC attendance produced estimates more consistent with surveillance data. The number of children living with HIV in Mozambique has been substantially underestimated because of biased routine ANC prevalence. Renewed focus on HIV surveillance among pregnant women would improve PMTCT coverage and pediatric HIV estimates.