Suchergebnisse

Abstract
The spring–summer 2022 mpox outbreak had over 50,000 cases globally, most of them in gay, bisexual, and other men who have sex with men (MSM). In response to vaccine shortages, several countries implemented dose-sparing vaccination strategies, stretching a full-dose vaccine vial into up to five fractional-dose vaccines. Recent studies have found mixed results regarding the effectiveness of the mpox vaccine, raising the question of the utility of dose-sparing strategies. We used an age- and risk-stratified mathematical model of an urban MSM population in the United States with ∼12% high-risk MSM to evaluate potential benefits from implementing dose-sparing vaccination strategies in which a full dose is divided into 3.5 fractional doses. We found that results strongly depend on the fractional-dose vaccine effectiveness (VE) and vaccine supply. With very limited vaccines available, enough to protect with a full dose approximately one-third of the high-risk population, dose-sparing strategies are more beneficial provided that fractional doses preserved at least 40% of full-dose effectiveness (34% absolute VE), projecting 13% (34% VE) to 70% (68% absolute VE) fewer infections than full-dose strategies. In contrast, if vaccine supply is enough to cover the majority of the high-risk population, dose-sparing strategies can be outperformed by full-dose strategies. Scenarios in which fractional dosing was 34% efficacious resulted in almost three times more infections than full dosing. Our analysis suggests that when mpox vaccine supply is limited and fractional-dose vaccination retains moderate effectiveness, there are meaningful health benefits from providing a smaller dose to a larger number of people in the high-risk population. These findings should inform the public-health response to future mpox outbreaks.

Abstract
Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counterfactual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American-Indian or Alaska-Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.

AbstractIntroductionPromising HIV vaccine candidates are steadily progressing through the clinical trial pipeline. Once available, HIV vaccines will be an important complement but also potential competitor to other biomedical prevention tools such as pre‐exposure prophylaxis (PrEP). Accordingly, the value of HIV vaccines and the policies for rollout may depend on that interplay and tradeoffs with utilization of existing products. In this economic modelling analysis, we estimate the cost‐effectiveness of HIV vaccines considering their potential interaction with PrEP and condom use.MethodsWe developed a dynamic model of HIV transmission among the men who have sex with men population (MSM), aged 15‐64 years, in Seattle, WA offered PrEP and HIV vaccine over a time horizon of 2025‐2045. A healthcare sector perspective with annual discount rate of 3% for costs (2017 USD) and quality‐adjusted life years (QALYs) was used. The primary economic endpoint is the incremental cost‐effectiveness ratio (ICER) when compared to no HIV vaccine availability.ResultsHIV vaccines improved population health and increased healthcare costs. Vaccination campaigns achieving 90% coverage of high‐risk men and 60% coverage of other men within five years of introduction are projected to avoid 40% of new HIV infections between 2025 and 2045. This increased total healthcare costs by $30 million, with some PrEP costs shifted to HIV vaccine spending. HIV vaccines are estimated to have an ICER of $42,473/QALY, considered cost‐effective using a threshold of $150,000/QALY. Results were most sensitive to HIV vaccine efficacy and future changes in the cost of PrEP drugs. Sensitivity analysis found ranges of 30‐70% HIV vaccine efficacy remained cost‐effective. Results were also sensitive to reductions in condom use among PrEP and vaccine users.ConclusionsAccess to an HIV vaccine is desirable as it could increase the overall effectiveness of combination HIV prevention efforts and improve population health. Planning for the rollout and scale‐up of HIV vaccines should carefully consider the design of policies that guide interactions between vaccine and PrEP utilization and potential competition.

AbstractIntroductionMathematical models of HIV have been uniquely important in directing and evaluating HIV policy. Transgender and nonbinary people are disproportionately impacted by HIV; however, few mathematical models of HIV transmission have been published that are inclusive of transgender and nonbinary populations. This commentary discusses current structural challenges to developing robust and accurate trans‐inclusive models and identifies opportunities for future research and policy, with a focus on examples from the United States.DiscussionAs of April 2024, only seven published mathematical models of HIV transmission include transgender people. Existing models have several notable limitations and biases that limit their utility for informing public health intervention. Notably, no models include transgender men or nonbinary individuals, despite these populations being disproportionately impacted by HIV relative to cisgender populations. In addition, existing mathematical models of HIV transmission do not accurately represent the sexual network of transgender people. Data availability and quality remain a significant barrier to the development of accurate trans‐inclusive mathematical models of HIV. Using a community‐engaged approach, we developed a modelling framework that addresses the limitations of existing model and to highlight how data availability and quality limit the utility of mathematical models for transgender populations.ConclusionsModelling is an important tool for HIV prevention planning and a key step towards informing public health interventions, programming and policies for transgender populations. Our modelling framework underscores the importance of accurate trans‐inclusive data collection methodologies, since the relevance of these analyses for informing public health decision‐making is strongly dependent on the validity of the model parameterization and calibration targets. Adopting gender‐inclusive and gender‐specific approaches starting from the development and data collection stages of research can provide insights into how interventions, programming and policies can distinguish unique health needs across all gender groups. Moreover, in light of the data structure limitations, designing longitudinal surveillance data systems and probability samples will be critical to fill key research gaps, highlight progress and provide additional rigour to the current evidence. Investments and initiatives like Ending the HIV Epidemic in the United States can be further expanded and are highly needed to prioritize and value transgender populations across funding structures, goals and outcome measures.

AbstractIntroductionHIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV‐positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets.MethodsWe used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets – 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed – or UNAIDS 90‐90‐90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020.ResultsTo reduce the HIV incidence rate by 20% and 50% after five years (compared with the base‐case at the same time point), the proportion of all HIV‐positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90‐90‐90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively.ConclusionsSubstantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre‐exposure prophylaxis for MSM.

AbstractIntroductionLong‐acting injectable cabotegravir (CAB‐LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre‐exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB‐LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics.MethodsThree risk‐stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person‐years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB‐LA users and by switching different proportions of TDF/FTC users to CAB‐LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only.ResultsIncreasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB‐LA users among PrEP‐eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5–10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP‐indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively.ConclusionsAchieving high PrEP coverage by offering CAB‐LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands).