Sources of Human Immunodeficiency Virus Infections Among Men Who Have Sex With Men With a Migration Background: A Viral Phylogenetic Case Study in Amsterdam, The Netherlands.

BACKGROUND: Men and women with a migration background comprise an increasing proportion of incident human immunodeficiency virus (HIV) cases across Western Europe. METHODS: To characterize sources of transmission in local transmission chains, we used partial HIV consensus sequences with linked demographic and clinical data from the opt-out AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort of people with HIV in the Netherlands and identified phylogenetically and epidemiologically possible HIV transmission pairs in Amsterdam. We interpreted these in the context of estimated infection dates, and quantified population-level sources of transmission to foreign-born and Dutch-born Amsterdam men who have sex with men (MSM) within Amsterdam transmission chains. RESULTS: We estimate that Dutch-born MSM were the predominant sources of infections among all Amsterdam MSM who acquired their infection locally in 2010-2021, and among almost all foreign-born Amsterdam MSM subpopulations. Stratifying by 2-year intervals indicated time trends in transmission dynamics, with a majority of infections originating from foreign-born MSM since 2016, although uncertainty ranges remained wide. CONCLUSIONS: Native-born MSM have predominantly driven HIV transmissions in Amsterdam in 2010-2021. However, in the context of rapidly declining incidence in Amsterdam, the contribution from foreign-born MSM living in Amsterdam is increasing, with some evidence that most local transmissions have been from foreign-born Amsterdam MSM since 2016.

Inferring HIV transmission patterns from viral deep-sequence data via latent typed point processes.

Viral deep-sequencing data play a crucial role toward understanding disease transmission network flows, providing higher resolution compared to standard Sanger sequencing. To more fully utilize these rich data and account for the uncertainties in outcomes from phylogenetic analyses, we propose a spatial Poisson process model to uncover human immunodeficiency virus (HIV) transmission flow patterns at the population level. We represent pairings of individuals with viral sequence data as typed points, with coordinates representing covariates such as gender and age and point types representing the unobserved transmission statuses (linkage and direction). Points are associated with observed scores on the strength of evidence for each transmission status that are obtained through standard deep-sequence phylogenetic analysis. Our method is able to jointly infer the latent transmission statuses for all pairings and the transmission flow surface on the source-recipient covariate space. In contrast to existing methods, our framework does not require preclassification of the transmission statuses of data points, and instead learns them probabilistically through a fully Bayesian inference scheme. By directly modeling continuous spatial processes with smooth densities, our method enjoys significant computational advantages compared to previous methods that rely on discretization of the covariate space. We demonstrate that our framework can capture age structures in HIV transmission at high resolution, bringing valuable insights in a case study on viral deep-sequencing data from Southern Uganda.

The effectiveness of Hope Groups, a mental health, parenting support, and violence prevention program for families affected by the war in Ukraine: Findings from a pre-post study.

Background: Nearly one in six children lived in war zones in 2023. Evidence-based psychosocial and parenting support has potential to mitigate negative impacts for parents and children co-exposed to war and displacement, especially in relation to mental health and harsh parenting reactions. In the current war in Ukraine, local mental health experts co-created and evaluated, with global experts, the effectiveness of psychosocial and parenting support groups, called 'Hope Groups' on improvements in mental health, positive parenting, and violence against children. This paper aimed to assess the effectiveness of psychosocial and parenting support groups, called 'Hope Groups,' on improvements in caregiver mental health, positive parenting, and prevention of violence against children, for families affected by the war in Ukraine, using a pre/post study design. Methods: Participants (n = 577) included Ukrainian caregivers, 66% (381) of whom were parents and co-residing caregivers of children ages 0-17, while the remaining 34% were non-resident informal caregivers. Internally displaced, externally displaced, and those living at-home in war-torn regions were invited to groups by trained Ukrainian peer facilitators. Using a pre-post design, we compared individual level frequency measures at three time-points - baseline, midline, and endline, to assess changes in 4 mental health, and 9 parenting and child health outcomes. We analyzed these outcomes using paired t-tests to compare outcomes at baseline-to-midline (after 4-sessions) and baseline-to-endline (after 10-sessions), which estimated the mean changes in days per week and associated percent change, during the respective periods; we quantified uncertainties using bias-corrected and accelerated (BCa) bootstrapping with 95% uncertainty ranges for baseline-midline and baseline-endline estimates. We used this same approach for stratified analyses to assess potential effect modification by displacement status and facilitator type. We further used linear models to adjust for age and sex. Findings: Compared to baseline, every mental health, parenting, and child health outcome improved significantly at midline and endline. Mental health ratings showed endline reductions in depressive symptoms of 56.8% (95% CI: -59.0,-54.3; -1.8 days/week), and increases in hopefulness, coping with grief, and self-care, ranging from 62.0% (95% CI: 53.6,71.3; 2.2 days/week) to 77.0% (95% CI: 66.3,88.3; 2.2 days/week). Significant improvements in parenting and child health outcomes included monitoring children, reinforcing positive behavior, supporting child development, protecting child, nonviolent discipline, and child verbalizing emotions. By endline, emotional violence, physical violence, and child despondency had dropped by 57.7% (95% CI: -63.0%,-51.9; -1.3 days/week), 64.0% (95% CI: -79.0,-39.5; -0.22 days/week), and 51.9% (95% CI: -45.1,-57.9; -1.2 days/week), respectively. Outcomes stratified by displacement status remained significant across all groups, as did those according to facilitator type (lay versus professional). Interpretation: This study demonstrates preliminary evidence, using a brief survey and pre-post design as is appropriate for acute and early protracted emergency settings, of the feasibility and effectiveness of Hope Groups for war-affected Ukrainian caregivers, on improved mental health, positive parenting, and reduced violence against children.

Hope Groups: a protocol for a cluster randomized controlled trial of psychosocial, mental health, and parenting support groups for Ukrainian caregivers during war and conflict.

BACKGROUND: In 2021, more than two-thirds of the world's children lived in a conflict-affected country. In 2022, 13 million Ukrainians were forced to flee their homes after Russia's full-scale invasion. Hope Groups are a 12-session psychosocial, mental health, and parenting support intervention designed to strengthen parents, caregivers, and children affected by war and crisis. The primary objective of this study is to evaluate the effectiveness of Hope Groups among Ukrainians affected by war, compared to a wait-list control group. This protocol describes a promising decentralized intervention delivery model and an innovative research design, which estimates the causal effect of Hope Groups while prioritizing prompt delivery of beneficial services to war-affected participants. METHODS: This protocol describes a pragmatic cluster randomized controlled trial (RCT) among Ukrainians externally displaced, internally displaced within Ukraine, and living at home in war-affected areas. This study consists of 90 clusters with 4-7 participants per cluster, totaling approximately n = 450 participants. Intervention clusters will receive 12-session Hope Groups led by peer facilitators, and control clusters will be wait-listed to receive the intervention after the RCT concludes. Clusters will be matched on the facilitator performing recruitment and intervention delivery. Primary outcomes are caregiver mental health, violence against children, and positive parenting practices. Secondary outcomes include prevention of violence against women and caregiver and child well-being. Outcomes will be based on caregiver report and collected at baseline and endline (1-week post-intervention). Follow-up data will be collected among the intervention group at 6-8 weeks post-intervention, with aims for quasi-experimental follow-ups after 6 and 12 months, pending war circumstances and funding. Analyses will utilize matching techniques, Bayesian interim analyses, and multi-level modeling to estimate the causal effect of Hope Groups in comparison to wait-list controls. DISCUSSION: This study is the first known randomized trial of a psychosocial, mental health, and parenting intervention among Ukrainians affected by war. If results demonstrate effectiveness, Hope Groups hold the potential to be adapted and scaled to other populations affected by war and crisis worldwide. Additionally, methodologies described in this protocol could be utilized in crisis-setting research to simultaneously prioritize the estimation of causal effects and prompt delivery of beneficial interventions to crisis-affected populations. TRIAL REGISTRATION: This trial was registered on Open Science Framework on November 9, 2023. REGISTRATION: OSF.IO/UVJ67 .

Increasing intra- and inter-subtype HIV diversity despite declining HIV incidence in Uganda.

HIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.

Age and gender profiles of HIV infection burden and viraemia: novel metrics for HIV epidemic control in African populations with high antiretroviral therapy coverage.

Introduction: To prioritize and tailor interventions for ending AIDS by 2030 in Africa, it is important to characterize the population groups in which HIV viraemia is concentrating. Methods: We analysed HIV testing and viral load data collected between 2013-2019 from the open, population-based Rakai Community Cohort Study (RCCS) in Uganda, to estimate HIV seroprevalence and population viral suppression over time by gender, one-year age bands and residence in inland and fishing communities. All estimates were standardized to the underlying source population using census data. We then assessed 95-95-95 targets in their ability to identify the populations in which viraemia concentrates. Results: Following the implementation of Universal Test and Treat, the proportion of individuals with viraemia decreased from 4.9% (4.6%-5.3%) in 2013 to 1.9% (1.7%-2.2%) in 2019 in inland communities and from 19.1% (18.0%-20.4%) in 2013 to 4.7% (4.0%-5.5%) in 2019 in fishing communities. Viraemia did not concentrate in the age and gender groups furthest from achieving 95-95-95 targets. Instead, in both inland and fishing communities, women aged 25-29 and men aged 30-34 were the 5-year age groups that contributed most to population-level viraemia in 2019, despite these groups being close to or had already achieved 95-95-95 targets. Conclusions: The 95-95-95 targets provide a useful benchmark for monitoring progress towards HIV epidemic control, but do not contextualize underlying population structures and so may direct interventions towards groups that represent a marginal fraction of the population with viraemia.

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viraemia during Universal Test and Treat scale-up in Uganda: a population-based study.

INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. METHODS: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). CONCLUSIONS: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

Intrinsic randomness in epidemic modelling beyond statistical uncertainty.

Uncertainty can be classified as either aleatoric (intrinsic randomness) or epistemic (imperfect knowledge of parameters). The majority of frameworks assessing infectious disease risk consider only epistemic uncertainty. We only ever observe a single epidemic, and therefore cannot empirically determine aleatoric uncertainty. Here, we characterise both epistemic and aleatoric uncertainty using a time-varying general branching process. Our framework explicitly decomposes aleatoric variance into mechanistic components, quantifying the contribution to uncertainty produced by each factor in the epidemic process, and how these contributions vary over time. The aleatoric variance of an outbreak is itself a renewal equation where past variance affects future variance. We find that, superspreading is not necessary for substantial uncertainty, and profound variation in outbreak size can occur even without overdispersion in the offspring distribution (i.e. the distribution of the number of secondary infections an infected person produces). Aleatoric forecasting uncertainty grows dynamically and rapidly, and so forecasting using only epistemic uncertainty is a significant underestimate. Therefore, failure to account for aleatoric uncertainty will ensure that policymakers are misled about the substantially higher true extent of potential risk. We demonstrate our method, and the extent to which potential risk is underestimated, using two historical examples.