Current Work

For this project, we will further extend the previously calibrated/validated simulation model of HIV among MSM in Baltimore to incorporate explicit representation of rectal gonorrhea/chlamydia (NG/CT), modeled as a single entity, in parallel to the existing model of HIV transmission. NG/CT contribute to the increased risk and racial disparities in HIV among MSM[1]. We will explicitly and separately model transmission of NG/CT through the Baltimore MSM population, accounting for the fact that the selected STI will co-localize with HIV and will indeed increase the transmission risk of HIV in individuals harboring the NG/CT. We will calibrate the model to the estimated incidence and prevalence of NG/CT in Baltimore’s MSM population, including co-localization with HIV and the fact that, for many individuals, HIV infection is preceded/foreshadowed by infection with NG/CT (thereby making infection with NG/CT a potential target for PrEP initiation). We will use the model to demonstrate how NG/CT affects the dynamics of HIV among Baltimore’s MSM population. We will then project the potential impact of better STI care – including offering PrEP to individuals diagnosed with NG/CT – on HIV transmission in the city.

In this analysis, we will apply the methodology for adjusting CDC Medical Monitoring Project-based HIV care continuum estimates, developed earlier using data from the HIV Outpatient Survey, to the more robust NA-ACCORD clinical cohort data. This manuscript will examine the 5-year period from 2009-2014 to provide adjusted and more-representative estimate of the national HIV care continuum and compare these results to results from HIV NHSS laboratory surveillance.

The primary goal of this project is to use stochastic network modeling to estimate the proportion of HIV infections among MSM that are caused by prevalent STIs. HIV transmission in a dynamic sexual network of MSM will be modeled in the context of five STIs: urethral and rectal chlamydia, urethral and rectal gonorrhea, and syphilis. The proportion of HIV infections occurring among men with prevalent STI infection will be considered the population attributable fraction. Due to the uncertainty in estimates of transmission probabilities, we will conduct sensitivity analyses across a range of plausible values for increased susceptibility to HIV acquisition due to STI infection. 

This study will investigate the implications of race-specific PrEP uptake and adherence on HIV incidence and prevalence among white and black MSM in the United States. Model scenarios will explore the level of PrEP utilization needed to close the gap in HIV incidence between these two groups.

Comparing the Effects of STI Prevention The goal of this project will be to extend the population attributable fraction (PAF) work to assess the potential impact of STI screening on HIV incidence. Specifically, this project merges two existing CAMP-supported projects: the PAF model and the STI guidelines model. We will assess the downstream effect of implementation of the STI guidelines on HIV incidence among MSM due to increased risk of HIV transmission and acquisition in the presence of prevalent STI. This work will include the effects of gonorrhea and chlamydia at a minimum. If we are able to overcome the challenges of incorporating syphilis into the model then we will also assess the effects of testing and screening for syphilis. 

A major strategy for STI/HIV prevention has been network-based and partner-based targeting strategies for increasing screening, treatment, and linkage to other services. Disease intervention specialists (DIS) within health departments attempt to break onward STI transmission chains by offering treatment to a subset of named partners that may be contacted. While these DIS efforts have been successful in identifying and treating STIs, their population-level epidemiological impact and cost-effectiveness for men who have sex with men (MSM) has not been modeled robustly. In this modeling study, we will investigate these disease prevention approaches as used in the real world by local and state health departments. We will simulate the scale-up of DIS-based STI disease identification and treatment through sexual partnership networks of MSM. The goal will be to evaluate how DIS services may be optimally used compared to other potential STI testing and treatment approaches.

The goal of this project will be to extend the population attributable fraction (PAF) work to assess the cost-effectiveness of STI screening in terms of reducing HIV incidence. Specifically, this project merges two existing CAMP-supported projects: the PAF model and the STI guidelines model. We will assess the downstream effect of implementation of the STI guidelines on HIV incidence among MSM with respect to quality-adjusted life years (QALYs) gained under different STI testing scenarios.

The population-level prevention benefits of HIV PrEP will strongly depend on how the medication is used by those at substantial risk of infection. Questions remain about the potential of PrEP to achieve long-term reductions in HIV incidence among MSM given uncertainty about patterns of uptake, adherence, and discontinuation of the medication; these patterns will likely differ from the CDC’s clinical practice guidelines on PrEP indications and utilization. Deviations include: 1) the use of PrEP by MSM who self-select in using the medication but have no (or minimal) risk indications; 2) the non-use of PrEP by MSM with strong risk indications, based on either lack of awareness of PrEP or limited access to PrEP providers; 3) time-varying patterns of adherence (or non-adherence) to PrEP relative to time-varying patterns of high-risk sexual activity, compared to daily use recommended by CDC following FDA approval guidelines; and 4) heterogeneity in how MSM fully discontinue PrEP use unrelated to their ongoing risk indications, based on clinical, biological, or psychological reasons in stopping medication. In this study, we propose to build on the robust HIV PrEP implementation in our prior network-based simulation models to address questions of how longitudinal variation in these various factors could impact both the epidemiological impact and cost-effectiveness of HIV PrEP as a prevention intervention for MSM in the United States.

HIV testing is the cornerstone of HIV prevention. CDC recommends HIV testing at least annually for persons at risk of HIV infection. Previous modeling studies have suggested that HIV testing more frequently would be unlikely to be cost-effective at the population level. These models, however, did not incorporate the benefits of linkage to PrEP (soon after initiation of indicating risks) and immediate HIV treatment (for diagnosed infected persons) that would improve with increased testing. Our prior PrEP model also found that nearly half of at-risk MSM were missed by standard HIV testing frequencies that lead to PrEP evaluation. We propose to build on the existing model platform to investigate the HIV prevention benefits of a three-pronged strategy to reduce HIV incidence through: 1) more frequent diagnostic HIV testing; 2) immediate HIV treatment for persons with diagnosed acute and early HIV infection; and 3) PrEP for those who test negative but are at high risk. The project will evaluate the relative benefits of each of these components independently and in combination to identify the optimal mix of these strategies for both public health impact (number of infections averted) and efficiency (cost-effectiveness).

The primary goal of this project is to model the effect of different levels of PrEP coverage across strata of age, race, and geography. Risk screening tools have been found to perform deferentially by race, resulting in under-identification of black MSM with indications for PrEP. We propose to examine different scenarios of PrEP coverage in high-risk groups (e.g., offering PrEP to all black MSM under age 30) to assess the overall impact on HIV incidence at a national level.

Over the last few years safety and feasibility studies, modeling work and clinical trials have all indicated that PrEP can be a safe and effective intervention for the prevention of HIV among ASMM.  In our own modeling work focused on ASMM we have evaluated the potential impacts of changes in coverage and adherence as well as the impact of racial disparities along these dimensions. In addition to the direct befits of PrEP for HIV prevention among ASMM, PrEP may also be important and impactful as it could establish a lifelong norm of PrEP use and treatment seeking behavior.  

The potential importance of establishing PrEP use norms early was highlighted by our most recent modeling study which simultaneously modeled the Adult MSM population and the ASMM population.  We found that PrEP use among young adult MSM significantly reduced incidence among ASMM.  This finding suggested that, to the extent that ASMM can establish a norm of PreP use as they enter early adulthood, it could further prevent new infections among the next generation of ASMM.

This project will explore the implications of existing patterns of condom use and the potential for interventions for increasing condom use on population-level HIV outcomes among adolescent sexual minority males (ASMM). We will first examine temporal trends and differences across age and race/ethnicity in condom use among ASMM using data from the Youth Risk Behavioral Surveillance System and the American Men’s Internet Survey. Then, we will use our existing mathematical model of HIV transmission in this population to understand how the observed data may have contributed to the current HIV epidemic among ASMM and how ongoing trends and potential condom-related interventions may affect the future of the epidemic. Modeling analyses will be conducted in scenarios with varying levels of PrEP use to explore the impact of these two key prevention interventions separately and in combination.

In years 3 and 4, we developed a user-friendly transmission modeling tool designed to provide answers to the relationship between behavioral changes and STI incidence among US adolescents. This tool is heading into clearance and will then be publicly available. With this product, we propose to fulfill three aims:

1. Inform public health departments around the country about the existence of the tool, and provide guidance in its use.

2. Develop a case study that uses the tool to compare the projected impacts of a specific form of behavior change at the national level with that of a single jurisdiction, and interpret those results

3. Communicate to this audience the various unanticipated challenges we tackled on the development of the tool, and what they tell us about the state of STI surveillance and epidemiology for adolescents 

We aim to complete all three of these aims through a manuscript and accompanying presentations/webinars/workshops of some form.  Some remaining details of the case study and the dissemination methods are to be developed in consultation with DASH.

For this project, we will further extend the previously calibrated/validated simulation model of HIV among MSM in Baltimore to incorporate explicit representation of rectal gonorrhea/chlamydia (NG/CT), modeled as a single entity, in parallel to the existing model of HIV transmission. NG/CT contribute to the increased risk and racial disparities in HIV among MSM[1]. We will explicitly and separately model transmission of NG/CT through the Baltimore MSM population, accounting for the fact that the selected STI will co-localize with HIV and will indeed increase the transmission risk of HIV in individuals harboring the NG/CT. We will calibrate the model to the estimated incidence and prevalence of NG/CT in Baltimore’s MSM population, including co-localization with HIV and the fact that, for many individuals, HIV infection is preceded/foreshadowed by infection with NG/CT (thereby making infection with NG/CT a potential target for PrEP initiation). We will use the model to demonstrate how NG/CT affects the dynamics of HIV among Baltimore’s MSM population. We will then project the potential impact of better STI care – including offering PrEP to individuals diagnosed with NG/CT – on HIV transmission in the city.

The primary goal of this project is to use stochastic network modeling to estimate the proportion of HIV infections among MSM that are caused by prevalent STIs. HIV transmission in a dynamic sexual network of MSM will be modeled in the context of five STIs: urethral and rectal chlamydia, urethral and rectal gonorrhea, and syphilis. The proportion of HIV infections occurring among men with prevalent STI infection will be considered the population attributable fraction. Due to the uncertainty in estimates of transmission probabilities, we will conduct sensitivity analyses across a range of plausible values for increased susceptibility to HIV acquisition due to STI infection. 

This study will examine the role of expedited partner therapy (EPT) for STI prevention among MSM by extending our HIV/STI modeling platform to include this new STI control technique for site-specific gonorrhea, chlamydia, and syphilis. EPT is not currently recommended for MSM by CDC and thus traditional epidemiological studies are not We propose an analysis to use this platform to test how EPT could be used alone and alongside other STI prevention interventions to reduce disease incidence. 

In the proposed models, EPT will be simulated as the immediate provision of antibiotic medication to the current sexual partners of those MSM who are routinely diagnosed and treated for those STIs in clinical settings. Parameters in these models will include the coverage fraction for EPT (the proportion of MSM with EPT-indicated partners who accept it) and medication uptake among those partners. Sensitivity analyses for these models could explore how EPT targeted at STI-infected MSM with particular partnership configurations could maximize the epidemiological impact (infections averted) and efficiency (number needed to treat) of that intervention. With collaboration from DSTDP colleagues at CDC, these outcomes could be directly translated into a cost-effectiveness analysis comparing standard clinic-based testing and treatment of STIs versus EPT. The paper may also include an online web-based modeling tool that will allow STI program officials at local jurisdictions to explore the potential impact, efficiency, and cost-effectiveness of EPT to be integrated within their STI prevention programs. This will be based on the design and content of the web tool for our Year 2 paper [http://prism.shinyapps.io/cdc-prep-guidelines].

MSM in the United States are disproportionately affected by the STI epidemic. In previous work, we have demonstrated the efficacy of HIV preexposure prophylaxis (PrEP) for STI prevention thanks to the recommended STI screening process for PrEP users. Men who are eligible for PrEP engage in certain risk behaviors for both HIV and STI transmission, making them good candidates for targeted STI testing. There is a particular need for modeling the potential impact of various targeting and intervention programs on STI incidence in this key population. We extend our existing agent-based mathematical model of rectal and urogenital HIV and STD transmission to include syphilis with an aim to evaluate the effect of the current STD screening recommendations referenced in the CDC STI treatment guidelines and other potential targeting mechanisms on STI incidence for MSM.

Although these recommendations have been present for a long period of time, uptake of STI testing in this population has been suboptimal. Parameters in these models will include the coverage fraction for STI testing (the proportion of MSM with EPT-indicated partners who accept it) and adherence to recommended testing intervals. Sensitivity analyses for these models could explore the length of the recommended screening intervals for all sexually active and high-risk MSM, respectively, as well as potential definitions of “high-risk” that could maximize the epidemiological impact (infections averted) and efficiency (number needed to treat) of that intervention. With collaboration with DSTDP colleagues at CDC, we also aim to conduct an economic evaluation of these guidelines, appraising the economic impact of different recommended testing interval lengths.

Comparing the Effects of STI Prevention The goal of this project will be to extend the population attributable fraction (PAF) work to assess the potential impact of STI screening on HIV incidence. Specifically, this project merges two existing CAMP-supported projects: the PAF model and the STI guidelines model. We will assess the downstream effect of implementation of the STI guidelines on HIV incidence among MSM due to increased risk of HIV transmission and acquisition in the presence of prevalent STI. This work will include the effects of gonorrhea and chlamydia at a minimum. If we are able to overcome the challenges of incorporating syphilis into the model then we will also assess the effects of testing and screening for syphilis. 

A major strategy for STI/HIV prevention has been network-based and partner-based targeting strategies for increasing screening, treatment, and linkage to other services. Disease intervention specialists (DIS) within health departments attempt to break onward STI transmission chains by offering treatment to a subset of named partners that may be contacted. While these DIS efforts have been successful in identifying and treating STIs, their population-level epidemiological impact and cost-effectiveness for men who have sex with men (MSM) has not been modeled robustly. In this modeling study, we will investigate these disease prevention approaches as used in the real world by local and state health departments. We will simulate the scale-up of DIS-based STI disease identification and treatment through sexual partnership networks of MSM. The goal will be to evaluate how DIS services may be optimally used compared to other potential STI testing and treatment approaches.

The goal of this project will be to extend the population attributable fraction (PAF) work to assess the cost-effectiveness of STI screening in terms of reducing HIV incidence. Specifically, this project merges two existing CAMP-supported projects: the PAF model and the STI guidelines model. We will assess the downstream effect of implementation of the STI guidelines on HIV incidence among MSM with respect to quality-adjusted life years (QALYs) gained under different STI testing scenarios.

The population-level prevention benefits of HIV PrEP will strongly depend on how the medication is used by those at substantial risk of infection. Questions remain about the potential of PrEP to achieve long-term reductions in HIV incidence among MSM given uncertainty about patterns of uptake, adherence, and discontinuation of the medication; these patterns will likely differ from the CDC’s clinical practice guidelines on PrEP indications and utilization. Deviations include: 1) the use of PrEP by MSM who self-select in using the medication but have no (or minimal) risk indications; 2) the non-use of PrEP by MSM with strong risk indications, based on either lack of awareness of PrEP or limited access to PrEP providers; 3) time-varying patterns of adherence (or non-adherence) to PrEP relative to time-varying patterns of high-risk sexual activity, compared to daily use recommended by CDC following FDA approval guidelines; and 4) heterogeneity in how MSM fully discontinue PrEP use unrelated to their ongoing risk indications, based on clinical, biological, or psychological reasons in stopping medication. In this study, we propose to build on the robust HIV PrEP implementation in our prior network-based simulation models to address questions of how longitudinal variation in these various factors could impact both the epidemiological impact and cost-effectiveness of HIV PrEP as a prevention intervention for MSM in the United States.

HIV testing is the cornerstone of HIV prevention. CDC recommends HIV testing at least annually for persons at risk of HIV infection. Previous modeling studies have suggested that HIV testing more frequently would be unlikely to be cost-effective at the population level. These models, however, did not incorporate the benefits of linkage to PrEP (soon after initiation of indicating risks) and immediate HIV treatment (for diagnosed infected persons) that would improve with increased testing. Our prior PrEP model also found that nearly half of at-risk MSM were missed by standard HIV testing frequencies that lead to PrEP evaluation. We propose to build on the existing model platform to investigate the HIV prevention benefits of a three-pronged strategy to reduce HIV incidence through: 1) more frequent diagnostic HIV testing; 2) immediate HIV treatment for persons with diagnosed acute and early HIV infection; and 3) PrEP for those who test negative but are at high risk. The project will evaluate the relative benefits of each of these components independently and in combination to identify the optimal mix of these strategies for both public health impact (number of infections averted) and efficiency (cost-effectiveness).

The primary goal of this project is to model the effect of different levels of PrEP coverage across strata of age, race, and geography. Risk screening tools have been found to perform deferentially by race, resulting in under-identification of black MSM with indications for PrEP. We propose to examine different scenarios of PrEP coverage in high-risk groups (e.g., offering PrEP to all black MSM under age 30) to assess the overall impact on HIV incidence at a national level.

In years 3 and 4, we developed a user-friendly transmission modeling tool designed to provide answers to the relationship between behavioral changes and STI incidence among US adolescents. This tool is heading into clearance and will then be publicly available. With this product, we propose to fulfill three aims:

1. Inform public health departments around the country about the existence of the tool, and provide guidance in its use.

2. Develop a case study that uses the tool to compare the projected impacts of a specific form of behavior change at the national level with that of a single jurisdiction, and interpret those results

3. Communicate to this audience the various unanticipated challenges we tackled on the development of the tool, and what they tell us about the state of STI surveillance and epidemiology for adolescents 

We aim to complete all three of these aims through a manuscript and accompanying presentations/webinars/workshops of some form.  Some remaining details of the case study and the dissemination methods are to be developed in consultation with DASH.

We propose to assess the impact of changes in risk behaviors among adolescents by race, based on a recent 10-year trend analysis of the YRBS. This analysis demonstrated significant reductions in risk behaviors (proportion of adolescents ever having sex, numbers of partners, those reporting being currently sexually active) among Black and Hispanic adolescents. On the other hand, it demonstrated decreased condom use among White adolescents. This project will project the levels of gonorrhea and chlamydia incidence over ten years in the absence of those changes, as well as the levels expected in their presence.  Our analyses will focus on heterosexually active adolescents. We will project outcomes specific to race/ethnicity groups, and work with DASH partners to estimate the cost or savings associated with each outcome.

We propose to assess the impact of changes in risk behaviors among adolescents by race, based on a recent 10-year trend analysis of the YRBS. This analysis demonstrated significant reductions in risk behaviors (proportion of adolescents ever having sex, numbers of partners, those reporting being currently sexually active) among Black and Hispanic adolescents. On the other hand, it demonstrated decreased condom use among White adolescents. This project will project the numbers of pregnancy over ten years in the absence of those changes, as well as the numbers expected in their presence.  Our analyses will focus on heterosexually active adolescents. We will project outcomes specific to race/ethnicity groups, and work with DASH partners to estimate the cost or savings associated with each outcome.

This modeling study will extend the work of our initial modeling efforts for adolescent MSM, which have been investigating the role of PrEP scale-up on HIV incidence in this group, by examining age-specific outcomes. The current adolescent model tracks 13 to 18 year olds explicitly, but does not simulate their disease dynamics during adulthood, when the downstream impact of prevention interventions could be still accrued. We will expand the adolescent model to be able to capture extended impact of these interventions on adolescents as they advance as far as age 40. Considering this extended model will allow us to consider how lifetime incidence of HIV is impacted by engaging adolescents with PrEP, as well as identify the number needed to treat in the combined population.

Over the last few years safety and feasibility studies, modeling work and clinical trials have all indicated that PrEP can be a safe and effective intervention for the prevention of HIV among ASMM.  In our own modeling work focused on ASMM we have evaluated the potential impacts of changes in coverage and adherence as well as the impact of racial disparities along these dimensions. In addition to the direct befits of PrEP for HIV prevention among ASMM, PrEP may also be important and impactful as it could establish a lifelong norm of PrEP use and treatment seeking behavior.  

The potential importance of establishing PrEP use norms early was highlighted by our most recent modeling study which simultaneously modeled the Adult MSM population and the ASMM population.  We found that PrEP use among young adult MSM significantly reduced incidence among ASMM.  This finding suggested that, to the extent that ASMM can establish a norm of PreP use as they enter early adulthood, it could further prevent new infections among the next generation of ASMM.

This project will explore the implications of existing patterns of condom use and the potential for interventions for increasing condom use on population-level HIV outcomes among adolescent sexual minority males (ASMM). We will first examine temporal trends and differences across age and race/ethnicity in condom use among ASMM using data from the Youth Risk Behavioral Surveillance System and the American Men’s Internet Survey. Then, we will use our existing mathematical model of HIV transmission in this population to understand how the observed data may have contributed to the current HIV epidemic among ASMM and how ongoing trends and potential condom-related interventions may affect the future of the epidemic. Modeling analyses will be conducted in scenarios with varying levels of PrEP use to explore the impact of these two key prevention interventions separately and in combination.

In years 3 and 4, we developed a user-friendly transmission modeling tool designed to provide answers to the relationship between behavioral changes and STI incidence among US adolescents. This tool is heading into clearance and will then be publicly available. With this product, we propose to fulfill three aims:

1. Inform public health departments around the country about the existence of the tool, and provide guidance in its use.

2. Develop a case study that uses the tool to compare the projected impacts of a specific form of behavior change at the national level with that of a single jurisdiction, and interpret those results

3. Communicate to this audience the various unanticipated challenges we tackled on the development of the tool, and what they tell us about the state of STI surveillance and epidemiology for adolescents 

We aim to complete all three of these aims through a manuscript and accompanying presentations/webinars/workshops of some form.  Some remaining details of the case study and the dissemination methods are to be developed in consultation with DASH.

We propose to assess the impact of changes in risk behaviors among adolescents by race, based on a recent 10-year trend analysis of the YRBS. This analysis demonstrated significant reductions in risk behaviors (proportion of adolescents ever having sex, numbers of partners, those reporting being currently sexually active) among Black and Hispanic adolescents. On the other hand, it demonstrated decreased condom use among White adolescents. This project will project the levels of gonorrhea and chlamydia incidence over ten years in the absence of those changes, as well as the levels expected in their presence.  Our analyses will focus on heterosexually active adolescents. We will project outcomes specific to race/ethnicity groups, and work with DASH partners to estimate the cost or savings associated with each outcome.

We propose to assess the impact of changes in risk behaviors among adolescents by race, based on a recent 10-year trend analysis of the YRBS. This analysis demonstrated significant reductions in risk behaviors (proportion of adolescents ever having sex, numbers of partners, those reporting being currently sexually active) among Black and Hispanic adolescents. On the other hand, it demonstrated decreased condom use among White adolescents. This project will project the numbers of pregnancy over ten years in the absence of those changes, as well as the numbers expected in their presence.  Our analyses will focus on heterosexually active adolescents. We will project outcomes specific to race/ethnicity groups, and work with DASH partners to estimate the cost or savings associated with each outcome.

In addition to infant vaccination, the Advisory Committee on Immunization Practices (ACIP) recommends adults at high risk of infection (injection drug users, men who have sex with men, individuals with HIV infection, etc.) be vaccinated against hepatitis B vaccine (HBV).  However, the list of high-risk individuals included in the current recommendations is long and includes adults with a variety of health conditions and risk behaviors, which could lead to confusion or challenges in implementation among providers.  Estimates from the National Health Interview Survey indicate only 32.9% of adults aged 19-49 and 15.9% of adults 50 years of age or older have received three doses (the required amount to receive optimal levels of seroprotection) of the HepB vaccine.  This project will assess several alternative strategies that aim to simplify HepB vaccine recommendations, increase vaccine coverage among adults and reduce the overall rate of new HBV infections.  The alternative strategies will be 1) universal vaccination of all adults; 2) targeted vaccination among defined age categories and 3) targeted vaccination among specific geographic regions.

Currently, adults who receive a hepatitis B vaccination typically receive a 3-dose series over 6 months.  However, a large, multi-site cohort study reported only 64% of adults who began the vaccine series actually received all 3 doses and only 81% received two doses, indicating many adults who start the current vaccine series remain at risk for HBV infection.  Additionally, there is evidence that older adults, diabetic persons, persons with renal disease, obese persons and smokers may have a reduced response to the ENGERIX-B or Recombivax-HB series.  In 2017, the U.S. Food and Drug Administration approved the use of HEPLISAV-B, a 2-dose vaccine series that can be administered over one month.  This project will determine which risk groups could most benefit from preferentially receiving the HEPLISAV-B vaccine instead of the currently administered 3-dose series.

A previous model used to quantify hepatitis B virus (HBV) disease burden and vaccination impact estimated the total number of persons who died from HBV-related causes for the year 2000. However, there have been significant changes in HBV epidemiology since 2000, including an increase in infant vaccine coverage to 90.5% in 2016, high disease burden from foreign-born persons, and an emerging epidemic among adults with a history of incarceration and/or who inject drugs. In 2016, 14.7% of liver transplant recipients tested positive for HBV. This project aims to estimate annual US chronic hepatitis B mortality (all-cause and cause-specific) and associated costs in the present year (2018) and possibly at a future time point (2038).

Our primary goal is to estimate the potential impact (and key determinants of impact) for selected TB control interventions in four states– California, New York, Texas and Florida. We propose to use our modeling framework to study the potential impact of specific TB interventions, namely (1) improved contact investigation, (2) expanded treatment of latent TB infection, and (3) enhanced screening and treatment of immigrants (as they enter) and other high-risk groups. For each intervention (individually and in combination), we will estimate the impact in terms of potential reduction in TB incidence over the coming five years, relative to a baseline in which current trends are continued. While we will not perform a full economic costing of each intervention, we will estimate the number of key resources required (e.g., drug doses, number of physician visits, number of hospitalizations, number of contacts visited), which could be combined with unit cost data to provide a rough estimate of cost-effectiveness. The impact of specific interventions can vary considerably between states; our model will be able to identify such differences, and help inform optimal interventions at the state-level. Furthermore, given that we have an individual-based modeling framework, it is possible for us to estimate the impact of interventions (e.g., preventive therapy, contact investigation) that are individually focused, and to evaluate how that impact might differ from one state to the next. 

Cherng S,Shrestha S,Reynolds S,Hill A,Marks S,Kelly J,Dowdy D

Substantial geographic heterogeneity in the distribution of TB risk factors contribute substantially to observed differences in the incidence and prevalence of TB in the US by state.  Such heterogeneity can have direct implications for TB interventions. In particular, impact and effectiveness of interventions estimated at the national level may not translate appropriately to state-level requirements. A quantitative understanding of geographic heterogeneity of TB-risk factors at a more granular level can therefore complement a targeted intervention approach. The primary research goal is to quantify the role of TB risk factors (including: Region of birth, HIV, diabetes, incarceration, and homeless status). This will require estimating the size of each subpopulation by state, the within-group incidence, and the overall contribution of the risk factor on state-level TB incidence. Additionally, we will calculate the population attributable fractions and total cases that could be averted based on the best performing state among California, Texas, Florida, or New York by subpopulation in order to illustrate and quantify a range of best-case scenarios. 

The primary purpose of this web tool is to evaluate the “heterogeneity-attributable fraction” of TB incidence in each of the 50 states.  Building on our model of state-level heterogeneity in TB across key populations, we will develop a 508-compliant web tool that will make customized results available to public users, including state-level TB controllers. Once complete, users of this web tool will be able to see state- and population-specific estimates of the heterogeneity-attributable fraction of TB, thus enabling them to make better decisions about the appropriate direction of resources at the state level.

The primary purpose of this project is to evaluate the costs of two TB interventions: (1) Targeted testing and treatment (2) Extended contact investigation -- in each of the 50 states.  Building on our model of state-level heterogeneity in TB across key populations, we will compile various cost and QALY input data sources, conduct sensitivity analyses and produce state- and population-specific estimates of the TB intervention costs and cost-effectiveness, thus enabling them to make better decisions about the appropriate direction of resources at the state level. Our results will be integrated into an interactive web tool that will be made publicly available to decision-makers in all jurisdictions and supported with plain language summaries and simple user guides.

The primary aim of this project is to enable state-level TB controllers and public health officials to access model-based results and data (that we are developing) on the impact of state-level TB interventions in a user-friendly and interactive fashion. The states considered are California, Florida, New York, and Texas, which together contribute to more 50% of new TB cases in the United States. The interventions modeled are: (i) targeted testing and treatment of high-risk populations (consisting of non-US-born individuals, diabetics, HIV+, individuals that are homeless and incarcerated), and (ii) enhanced contact investigation.

The primary purpose of this project is to evaluate the costs and cost effectiveness of Targeted testing and treatment (TTT) for latent tuberculosis infection (LTBI) in California, Florida, New York, and Texas. Using previously developed TB transmission models, we estimated the numbers of individuals who would be tested by interferon-? release assay and would subsequently complete 3 months of directly observed LTBI treatment with rifapentine and isoniazid, assuming ambitious scale-up over one year to each of many target populations. For each target population, we projected costs (in 2016 dollars) and effectiveness (reduction in TB incidence over a ten-year period). We then used these projections to estimate, from the healthcare perspective, the incremental cost-effectiveness (cost per quality-adjusted-life-year [QALY] gained) associated with TTT of each key population by state. 

The primary goal of this project is to compare critical elements of NEEMA grantees’ domestic TB elimination models by: 1) conducting a series of coordinated modeling activities between the three modeling teams (Harvard, UCSF and JHU) using the test case of California, and 2) comparing and synthesizing critical evidence and assumptions used in the modeling activities. The purpose of these comparisons is to (i) understand differences in modeling approaches, evidence and assumptions used by models, and incidence predictions produced by each model; (ii) resolve these differences to the extent that a single approach or assumption is supported by empirical evidence; and (iii) identify major policy messages supported by a consensus of the modeling results. As part of this effort, CDC and all grantees agree that we should work to understand the individual models’ approaches to input parameters, assumptions made about TB epidemiology, and model outputs or results. The proposed activities described will provide a platform for understanding these components across the three models and displaying those components to CDC and other users in a comprehensible fashion.

The primary goal of this project is to provide comparable estimates regarding the impact of various novel and improved TB control interventions. All grantees will model the epidemiological and economic impact of an agreed-upon panel of policies in their specific geographic areas of interest. Interventions may include: real or hypothetical interventions such as TB vaccines, gold standard/high performing LTBI diagnostic tests, enhanced contact investigation, and active case finding.