Sarit A. Golub, Ph.D. - US grants

DESCRIPTION (provided by applicant): In neuropsychological research, a link has been made between substance dependence and deficits in frontal system (i.e. executive) functioning, including problems with decision-making, working memory, and impulse control. In behavioral research, a link has been made between self-reported executive function deficits (e.g. impulsivity, sensation seeking, myopia) and HIV risk behavior. However, little if any research has been conducted to bridge the gap between neuropsychological and behavioral research. A better understanding of how neurocognitive factors influence HIV risk-behavior is critical to prevention efforts, as these factors may be working against specific intervention strategies or moderating intervention effectiveness. However, many behavioral interventions focusing on the intersection of substance use and sexual risk-taking do not consider neurocognitive factors, even as they target symptoms related to them (e.g. poor decision- making, problems with impulse control). The current proposal is designed to examine the role of neurocognitive factors in determining HIV risk behavior among men who have sex with men (MSM). Specifically, the proposed project aims to: 1) Investigate the role of neurocognitive deficits in the relationship between drug use and sexual risk-taking among substance using MSM;2) Examine whether the interactions among different neurocognitive deficits (e.g. hypersensitivity to reward vs. poor response inhibition) are associated with different patterns of relationship between substance use and HIV risk behavior;3) Identify dispositional and contextual correlates that may promote or inhibit risk-behavior among individuals with particular neurocognitive profiles;and 4) Investigate the interaction between neurocognitive and dispositional factors in determining risky decision-making in the context of an experimental manipulation designed to increase reliance on the emotional "go" system. The proposed project will enroll 200 sexually active, substance using MSM. We will stratify the sample along two dimensions: HIV-status and risk-taking behavior. All participants will complete: a) a neuropsychological test battery designed to assess decision-making deficits and overall cognitive functioning;b) a self-report survey designed to assess dispositional and contextual factors that might impact risky decision- making;and c) a laboratory based real-time decision-making task in the presence or absence of an experimental manipulation. Our research design was developed to provide a nuanced understanding of the interaction between neurocognitive, dispositional, and contextual factors in determining HIV risk behavior among MSM, and will be critical to the development and adaptation of HIV prevention interventions for this population. PUBLIC HEALTH RELEVANCE: This project investigates the synergistic relationship among neurocognitive, dispositional, and contextual factors in HIV risk behavior. A better understanding how of neurocognitive factors impact substance use and HIV risk is critical to the development, implementation, and adaptation of effective HIV prevention efforts.

DESCRIPTION (provided by applicant): The proposed investigation seeks to examine the relationship between alcohol consumption patterns and sexuality among male and female emerging adults (ages 18-29) in New York City (NYC). We will undertake a longitudinal, prospective, mixed methods study, guided by the following three aims: (1) Test a new theoretical model, Conflict-Motivation Theory (CMT), which focuses on the role of sexual conflict in predicting risk-taking among emerging adults in the context of alcohol use. (2) Examine the role of developmental and individual (e.g. neurocognitive maturation, decision-making ability), social (e.g. social norms, attitudes, personal beliefs and values), and contextual (e.g. partner characteristics, alcohol dose, and setting) factors in shaping both sexual conflict and the associations among conflict, alcohol consumption, and risk-taking outlined in CMT. (3) Examine and identify the specific roles of gender (including gender roles, and sexual double standards), sexual orientation (including sexual identity and internalized homophobia), and race/ethnicity in shaping both sexual conflict and the associations among conflict, alcohol consumption, and risk-taking outlined in CMT. To achieve these aims, we will recruit and enroll 400 emerging adults into our study (stratified by gender, sexual orientation, and race/ethnicity) using Respondent Driven Sampling and conduct assessments of conflict, alcohol consumption patterns, and sexual risk-taking behaviors three times over the course of two years. Data analyses will utilize structural equation modeling, path analyses, and univariate and multivariate growth curve modeling to determine the relationships between these factors as a means of understanding the relationship between alcohol and sexuality and of evaluating the use of CMT to explain this relationship. Quantitative assessments (administered via Audio-CASI) will be complemented by our use of qualitative techniques to provide us with episode-specific data to help realize the relationships that we are assessing as well as to further understand contextual aspects of the relationship (e.g., reasons for combining alcohol and sexual activity, social contexts of drinking and sexual activity, etc.). Mixed-methods strategies will be used to examine the qualitative and quantitative data together in order to further test the proposed theoretical framework (CMT) and to better understand and explicate potential implications for intervention development. PUBLIC HEALTH RELEVANCE: The findings of this study will facilitate a more nuanced understanding of the reciprocal relationship between alcohol consumption patterns and sexuality, which will, in turn, inform prevention and intervention efforts. Specifically, the findings will inform preventions, interventions, and treatments designed to decrease alcohol use, abuse, and the problems associated with alcohol consumption and also inform efforts to decrease risky sex practices, alcohol-related sexual victimization, and the negative consequences often associated with combining alcohol and sexual activity.

DESCRIPTION (provided by applicant): Pre-exposure prophylaxis (PrEP) refers to daily or intermittent oral administration of antiretroviral drugs designed to protect high-risk HIV-negative individuals from infection. As PrEP is, at present, the most promising biomedical prevention tool, the Centers for Disease Control and Prevention (CDC) is currently reviewing PrEP data and developing detailed public health guidelines for its safe and effective use. Any roll-out of PrEP to MSM in the U.S. will require the development of messages that facilitate understanding of partial efficacy, proper administration, and sustained risk reduction practice. Although the swift development of PrEP-specific interventions is critical, we currently lack basic knowledge about unique cognitive, affective, and behavioral dynamics that may make a significant difference in both efficacy and effectiveness of PrEP as a biomedical prevention strategy. This project applies empirical findings and theoretical models from behavioral economics, social psychology, decision-sciences, health communication, and neuroeconomics to the development of PrEP messaging and communication strategies, in order to: (1) Examine the independent and cumulative impact of four elements of PrEP messaging - modality, frame, specificity, and messenger - on comprehension and acceptability of PrEP as a biomedical prevention strategy;(2) Estimate the impact of each of these factors on individual risk-perception and predicted sexual behavior in the context of PrEP use;(3) Identify individual-level factors, (i.e. demographics, risk tolerance, health numeracy), that might moderate the impact of message factors on comprehension, acceptability, risk perception, or risk compensation;and (4) Provide specific recommendations regarding the optimal message elements and communication strategies for PrEP in order to maximize comprehension and acceptability, while positively impacting risk perception and reducing the likelihood of risk compensation. To accomplish these aims, we will enroll 800 MSM living in the New York City area and randomly assign them to experimental conditions in a 2x2x2x2 factorial design. Data collection will include ACASI measures of outcomes (comprehension, acceptability, risk perception, and risk compensation) as well as potential moderators in four areas: (a) dispositional;(b) cognitive;(c) affective/motivational;and (d) behavioral (sexual risk and substance use). In addition, we will conduct 2 focus groups with each of 5 "special interest groups" (e.g. transgender women, serodiscordant couples) in order to gather detailed data regarding the specific needs, concerns, and issues among populations most likely to be offered PrEP. The proposed project has the potential to exert a sustained and powerful influence not only on the development of PrEP-specific messaging, but also on our understanding of the cognitive and affective processes underlying comprehension of risk-reduction messages, risk perception, and risk compensation. PUBLIC HEALTH RELEVANCE: Pre-exposure prophylaxis (PrEP) is a new biomedical approach to HIV prevention with the potential to become a powerful tool. This study examines specific elements of PrEP messaging and communication hypothesized to have a significant impact on comprehension, acceptability, risk perception, and risk compensation. Study findings have the potential to move the field toward a more interdisciplinary approach to understanding the behavioral mechanisms that underlie acceptability and adherence to biomedical prevention strategies.

DESCRIPTION (provided by applicant): The proposed investigation seeks to examine the relationship between alcohol consumption patterns and sexuality among male and female emerging adults (ages 18-29) in New York City (NYC). We will undertake a longitudinal, prospective, mixed methods study, guided by the following three aims: (1) Test a new theoretical model, Conflict-Motivation Theory (CMT), which focuses on the role of sexual conflict in predicting risk-taking among emerging adults in the context of alcohol use. (2) Examine the role of developmental and individual (e.g. neurocognitive maturation, decision-making ability), social (e.g. social norms, attitudes, personal beliefs and values), and contextual (e.g. partner characteristics, alcohol dose, and setting) factors in shaping both sexual conflict and the associations among conflict, alcohol consumption, and risk-taking outlined in CMT. (3) Examine and identify the specific roles of gender (including gender roles, and sexual double standards), sexual orientation (including sexual identity and internalized homophobia), and race/ethnicity in shaping both sexual conflict and the associations among conflict, alcohol consumption, and risk-taking outlined in CMT. To achieve these aims, we will recruit and enroll 400 emerging adults into our study (stratified by gender, sexual orientation, and race/ethnicity) using Respondent Driven Sampling and conduct assessments of conflict, alcohol consumption patterns, and sexual risk-taking behaviors three times over the course of two years. Data analyses will utilize structural equation modeling, path analyses, and univariate and multivariate growth curve modeling to determine the relationships between these factors as a means of understanding the relationship between alcohol and sexuality and of evaluating the use of CMT to explain this relationship. Quantitative assessments (administered via Audio-CASI) will be complemented by our use of qualitative techniques to provide us with episode-specific data to help realize the relationships that we are assessing as well as to further understand contextual aspects of the relationship (e.g., reasons for combining alcohol and sexual activity, social contexts of drinking and sexual activity, etc.). Mixed-methods strategies will be used to examine the qualitative and quantitative data together in order to further test the proposed theoretical framework (CMT) and to better understand and explicate potential implications for intervention development. PUBLIC HEALTH RELEVANCE: The findings of this study will facilitate a more nuanced understanding of the reciprocal relationship between alcohol consumption patterns and sexuality, which will, in turn, inform prevention and intervention efforts. Specifically, the findings will inform preventions, interventions, and treatments designed to decrease alcohol use, abuse, and the problems associated with alcohol consumption and also inform efforts to decrease risky sex practices, alcohol-related sexual victimization, and the negative consequences often associated with combining alcohol and sexual activity.

DESCRIPTION (provided by applicant): Pre-exposure prophylaxis (PrEP) refers to daily or intermittent oral administration of antiretroviral drugs designed to protect high-risk HIV-negative individuals from infection. As PrEP is, at present, the most promising biomedical HIV prevention tool, the Centers for Disease Control and Prevention (CDC) released interim guidance for health care providers in January 2011, and is expected to soon release detailed public health guidelines for its use. However, in order for PrEP to become an effective prevention tool, three critical factors must be addressed: a) acceptability, i.e., individuals who would benefit from PrEP must know about it and be willing to take it; b) adherence, i.e., individuals who choose to PrEP as a prevention strategy must take the pills as prescribed; and c) implementation, i.e., processes and protocols must be developed to allow for the integration of PrEP delivery and programs into real world settings in a way that is feasible, scalable, and realistic. The proposed project is a two-phase study, conducted in collaboration with the largest LGBT community health provider in New York City (NYC). This project will focus on three specific aims: 1) Identifying social and behavioral factors that are likely to influence PrEP implementation, acceptance, and use/adherence by MSM in NYC, including factors at individual-, community-, and organizational-levels; 2) Examining social and behavioral factors associated with disparities in access to prevention and care services among MSM in NYC that might directly impact PrEP implementation programs and policies; and 3) Evaluating an intervention in which PrEP is introduced, provided, and supported as part of a prevention package delivered in an community health center. To achieve these aims, the project will enroll high-risk MSM to test a two-stage behavioral intervention. First, eligible participants will be randomized to receive either basic information about PrEP availability or a targeted intervention designed to increase PrEP uptake. Second, participants who accept PrEP (regardless of condition) will be randomized to receive either basic adherence information or an enhanced PrEP adherence intervention. Participants will be followed quarterly for 12 months. Outcome variables will include: PrEP uptake, PrEP persistence, PrEP adherence (measured through self-report and biological measures), STI incidence, and self-reported risk behavior. The project is particularly innovative in that it combines an efficacy and effectiveness trial, testing a new intervention in the setting in which it would most feasibly be delivered, and pioneering a new approach to community-based collaboration and study design that can accelerate the pace of implementation science. The proposed project has the potential to exert a sustained and powerful influence not only on the effectiveness of PrEP interventions for MSM, but also on dissemination and scalability of a targeted intervention within community-based settings and in a manner that reduces disparities in access and maximizes cultural competence and acceptability.

? DESCRIPTION: Sustained release antiretrovirals (ARVs) for HIV prevention have tremendous potential to reduce rates of new infections, especially among high-risk individuals. Long-acting injectable (LAI) ARVs for PrEP have the potential to address several key barriers inherent in daily oral PrEP, including obviating the need for daily adherence and reducing disclosure concerns. Following successful protection experiments in the macaque model, Phase II trials of the LAI formulation of GSK-744 will begin in 2014, to be followed by Phase III efficacy trials in 2016. The proposed project is based on the premise that identifying key structural, behavioral, and social dynamics of LAI PrEP products and programs can make a significant impact on the future success of the prevention strategy and the speed with which an effective product is rolled out to the highest risk populations. This proposal builds on the investigators' expertise and involvement in both daily oral PrEP trials and LAI PrEP trials in the US to focus on structural, behavioral, and social factors that might inform optimal delivery of long- active ARV formulations for prevention. The project takes a multi-modal approach to identifying relevant healthcare system delivery factors, provider dynamics, and patient preferences that might impact long-acting ARV intervention delivery, including gathering data from three sources: a) patients participating in Phase II and Phase III LAI PrEP trials; b) patients and providers participating in an demonstration-implementation project for oral PrEP; and c) participants and providers from a population most likely to be targeted for LAI PrEP -- young men who have sex with men (YMSM) of color at highest risk for HIV infection. By triangulating data from these three sources, this project will provide vital information to guide both demonstration projects and broader-scale implementation efforts. The specific aims of this project are to: 1) Identify structural, behaviora, and social factors that might influence patient-level factors relevant to implementation of LAI ARV formulations for HIV prevention, such as uptake, persistence, and adherence to follow-up; 2) Identify structural, behavioral and social factors that might influence systems-level factors relevant to implementation of LAI ARV formulations for HIV prevention, such as provider training, protocol development, access, referral, prescription, and monitoring; and 3) Identify specific barriers and facilitators to the implementation of an LAI PrEP HIV prevention program for one of the top priority populations in the US -- highest-risk young men who have sex with men (YMSM). Our proposed deliverables are time-linked to product development milestones and include: 1) recommendations for social and behavioral measures to include in Phase III trials; 2) empirically-based guidelines that can form a blue-print for future demonstration and implementation efforts; and 3) specific recommendations for provider education, clinical guidance, and strategies for optimizing delivery of LAI PrEP to the populations at highest risk for infection. The proposed project will ensure that we are ready to fully realize the potential of new LAI ARV technology, maximizing its ability to make a significant and sustained impact on the epidemic.

? DESCRIPTION: Sustained release antiretrovirals (ARVs) for HIV prevention have tremendous potential to reduce rates of new infections, especially among high-risk individuals. Long-acting injectable (LAI) ARVs for PrEP have the potential to address several key barriers inherent in daily oral PrEP, including obviating the need for daily adherence and reducing disclosure concerns. Following successful protection experiments in the macaque model, Phase II trials of the LAI formulation of GSK-744 will begin in 2014, to be followed by Phase III efficacy trials in 2016. The proposed project is based on the premise that identifying key structural, behavioral, and social dynamics of LAI PrEP products and programs can make a significant impact on the future success of the prevention strategy and the speed with which an effective product is rolled out to the highest risk populations. This proposal builds on the investigators' expertise and involvement in both daily oral PrEP trials and LAI PrEP trials in the US to focus on structural, behavioral, and social factors that might inform optimal delivery of long- active ARV formulations for prevention. The project takes a multi-modal approach to identifying relevant healthcare system delivery factors, provider dynamics, and patient preferences that might impact long-acting ARV intervention delivery, including gathering data from three sources: a) patients participating in Phase II and Phase III LAI PrEP trials; b) patients and providers participating in an demonstration-implementation project for oral PrEP; and c) participants and providers from a population most likely to be targeted for LAI PrEP -- young men who have sex with men (YMSM) of color at highest risk for HIV infection. By triangulating data from these three sources, this project will provide vital information to guide both demonstration projects and broader-scale implementation efforts. The specific aims of this project are to: 1) Identify structural, behaviora, and social factors that might influence patient-level factors relevant to implementation of LAI ARV formulations for HIV prevention, such as uptake, persistence, and adherence to follow-up; 2) Identify structural, behavioral and social factors that might influence systems-level factors relevant to implementation of LAI ARV formulations for HIV prevention, such as provider training, protocol development, access, referral, prescription, and monitoring; and 3) Identify specific barriers and facilitators to the implementation of an LAI PrEP HIV prevention program for one of the top priority populations in the US -- highest-risk young men who have sex with men (YMSM). Our proposed deliverables are time-linked to product development milestones and include: 1) recommendations for social and behavioral measures to include in Phase III trials; 2) empirically-based guidelines that can form a blue-print for future demonstration and implementation efforts; and 3) specific recommendations for provider education, clinical guidance, and strategies for optimizing delivery of LAI PrEP to the populations at highest risk for infection. The proposed project will ensure that we are ready to fully realize the potential of new LAI ARV technology, maximizing its ability to make a significant and sustained impact on the epidemic.

7. PROJECT SUMMARY Transgender women (TW) are disproportionately impacted by HIV and have some of the highest incidence and prevalence rates in the US and around the world. PrEP has tremendous potential to reduce rates of HIV infection among TW; however, there is a striking lack of research on PrEP in this population. Data are urgently needed regarding the unique needs, concerns, HIV risk behavior patterns and health care utilization dynamics that impact PrEP initiation, persistence, and adherence among TW. In addition, more data are needed on adherence behavior and drug concentrations among TW, especially in the context of community concerns about drug-drug interactions (DDIs) between antiretrovirals and the estrogen formulations most commonly used by TW. This R21 study is based on the scientific premise that current gaps in the research literature limit the effective utilization of PrEP among TW, and that a better understanding of PrEP uptake, adherence and TFV levels in TW is critical to the development of optimal HIV prevention programs. The project leverages an existing cohort of TW on PrEP at an LGBT-focused community-based health center, in order to better understand and improve PrEP implementation efforts with this population. The specific aims of this R21 project are to: (1) Identify factors associated with PrEP initiation and persistence among a sample of TW with access to health care; (2) Identify correlates, motivators, and predictors associated with objective (i.e., TFV-DP levels) and self-report measures of PrEP adherence among a cohort of TW taking PrEP for at least three months; and (3) Examine the association between self-reported adherence, TFV-DP concentrations, and estradiol levels among TW on PrEP over a 6-month period. To accomplish these aims, we will conduct two complementary exploratory studies. First, we will conduct a detailed retrospective case/control chart review study, comparing 160 TW women who chose to initiate PrEP to 160 yoked TW who refused PrEP in the same 12-month period. Second, we will conduct a prospective cohort study, in which we will follow two cohorts of patients for 6- months: 1) TW who have been on PrEP for at least 3 months (n = 100); and 2) TW who have had access to PrEP services for at least 3 months but have refused PrEP (n = 50). Data collection will include medical record review, HIV/STI testing, self-reported and objective measures of PrEP adherence (i.e., measurement of TFV- DP concentrations), measurement of hormone levels and mode of administration (e.g., patch, tabs, injectable), and self-report survey data on psychosocial variables at enrollment, 3-month, and 6-month follow-up. In addition, we will enroll a subsample of TW using injectable estradiol to examine TFV-DP and hormone concentrations at trough (i.e., injection visit) and peak (i.e., 4-days post injection) levels to identify any potential fluctuations. This study would be the first to explore PrEP initiation, persistence, and adherence among a large cohort of TW in a real world setting and is poised to have an immediate, significant and sustained impact by identifying critical factors necessary to intervention to improve PrEP implementation and reduce HIV incidence.

7. PROJECT SUMMARY This project collaborates with the New York City Department of Health and Mental Hygiene (NYC DOHMH) to develop and test a field-based comprehensive sexual health intervention for HIV-exposed contacts notified by its Partner Services (i.e., HIV contact tracing) program. Individuals reached by PS programs are highest priority for linkage to HIV prevention/care services: 10-20% are newly diagnosed with HIV as a result of PS notification and the remainder are eligible and high priority for PrEP. Because they seek out highest-risk individuals in the field, PS programs have the potential to significantly reduce existing disparities in PrEP uptake and timely HIV care initiation by reaching populations that are currently under-engaged by traditional PrEP or HIV testing programs. The new Partner Services-Sexual Health (PS-SH) intervention offers a comprehensive sexual health package that includes HIV testing, STI testing, ARV/PrEP education and immediate medication start to all individuals receiving contact notification (i.e., being notified of a recent exposure to HIV). NYCDOHMH is collaborating on this research project to enable a scientifically rigorous test of the intervention?s efficacy and produce the highest quality data on implementation dynamics, cost-effectiveness, and affordability to inform dissemination and adaptation of the intervention, should it prove effective. The specific aims are to: (1) Pilot and refine a field-based comprehensive sexual health intervention delivered through the NYC DOHMH Partner Services Program. Under this aim, we will pilot the intervention in five highest prevalence NYC neighborhoods for 6-months (n = ~60), examine feasibility and acceptability, and refine the intervention process and protocols for the trial to test effectiveness at scale. (2) Examine the effectiveness of the Partner Services-Sexual Health (PS-SH) intervention in improving rates of HIV testing, linkage to HIV prevention/care, and PrEP uptake among highest risk contacts recently exposed to HIV. Under this aim, we will conduct a cross-sectional stepped wedge cluster randomized trial in which 12 clusters of NYC neighborhoods are exposed to the intervention sequentially, with three clusters moving from control to intervention every 6 months (n = 1150). Primary outcomes are HIV testing, timely PrEP/ARV uptake, and linkage to PrEP/HIV care. Secondary outcomes are STD testing and receipt of STD treatment (if indicated). (3) Conduct preliminary analyses of economic outcomes, including cost-allocation and affordability to allow other jurisdictions to make decisions about implementation. These analyses will include per-outcome cost-estimates, and will develop a blueprint for economic evaluation of the intervention including incremental cost-effectiveness and budget impact analyses for application locally and nationally. The proposed project is poised to have a significant and sustained impact on the field by: a) addressing a critical gap in the prevention/care continuum to reduce persistent disparities in the epidemic; and b) pioneering a collaborative implementation science approach to accelerate the dissemination of evidence-based practice models across the United States and internationally.

PROJECT SUMMARY Full Research Project 1 ? Liver Cancer Long-Term Adherence to Monitoring/Treatment in Underserved Asian Americans with Chronic HBV TU FCCC: Grace X. Ma, PhD (Co-Leader) and Nestor Esnaola, MD, MPH (Co-Leader, URM ESI) HC: Sarit A. Golub, PhD (Co-Leader) and Chibuzo Enemchukwu, MD (Co-Leader, URM ESI) Although Asian Americans make up 6% of total U.S. population, they account for over 50% of Americans with chronic hepatitis B (CHB), which is associated with 75% of hepatocellular carcinoma (HCC), the most common type of liver cancer. Asian Americans as a liver cancer disparity population are 8-13 times more likely to develop liver cancer with 60% higher death rate than non-Hispanic whites (NHWs). Research indicates that blood tests every six months and an abdominal ultrasound every 12 months, combined with antiviral treatment (e.g. entecavir or tenofovir) when appropriate, is the gold standard of care to reduce the risk of liver disease (including HCC). However, adherence to monitoring and antiviral treatment guidelines among Asian American patients with CHB is as low as 40% to 53%. Poor healthcare access and significant cultural barriers may prevent long-term adherence to monitoring and optimal treatment, placing Asian Americans at a disproportionately high risk for HCC and increased healthcare costs. Building on previous studies on a patient navigator-led intervention to improve monitoring and care among noncompliant Asian American with CHB, conducted by our established academic-clinical-community research team, we developed and pilot tested a virtual patient navigation toolkit system (VPN toolkit) to replace our traditional patient navigator-led CHB management. Since our preliminary data and other studies indicate that text messaging (TM) interventions have potential to significantly improve adherence to treatment across illnesses, we propose to test the effectiveness of TM versus enhanced mHealth intervention (VPN Toolkit + TM) designed to help sustain and improve long-term adherence (i.e., 24 months follow ups) to monitoring and antiviral treatment guidelines, thereby reducing cancer health disparities among underserved at-risk Asian Americans with CHB leveraging our existing cohort of CHB patients. The specific aims are: 1) Evaluate the comparative effectiveness of TM vs VPN+TM for improving long-term adherence to monitoring (doctor visit and blood tests) every six months (6- , 12-, 18-, and 24-month follow-ups) and ultrasound (at 12 and 24 months); 2) Compare the effectiveness of TM vs VPN+TM in improving and sustaining medication adherence (measured through self-report and electronic monitoring) among Asian Americans with CHB who meet antiviral treatment guidelines; 3) Examine mediators of intervention effectiveness, including dose-response (i.e., utilization of the TM and VPN toolkit), information (knowledge), motivation, and self-efficacy. Our comparative study of mHealth approaches will demonstrate how technology-based interventions can be integrated most effectively into real-world clinical settings to reduce HBV-related liver cancer disparities. If effective, this VPN+TM intervention is a highly disseminable intervention with the potential to have a significant impact on reducing viral-related cancer disparities among underserved Asian Americans and other highest-risk populations.

7. PROJECT SUMMARY/ABSTRACT There are a myriad of new HIV pre-exposure prophylaxis (PrEP) drug formulations and delivery modalities under clinical development, and it is expected that a range of biomedical HIV prevention options will soon be available. To enable these options to have maximum public health impact there is an urgent need to create biobehavioral infrastructure (i.e., empirically validated knowledge, guidelines, and tools) that will: a) allow the integration of these new options into existing PrEP delivery systems; b) support adherence and retention in an emerging HIV prevention service system; and c) promote health equity by ensuring that new prevention options expand HIV prevention coverage to highest priority populations. However, limited research exists that integrates lessons from existing implementation efforts for oral PrEP and develops data-driven tools that can be used by research and clinical practice to accelerate diffusion of proven prevention strategies. In response to that need, the specific aims of this project are to: (1) Synthesize intervention components of PrEP service delivery models in seven federally designated Ending the HIV Epidemic (EtHE) hotspot counties across the US, representing diverse geographical contexts, patient populations, and delivery settings; (2) Operationalize a set of PrEP service delivery process and outcome metrics than can be used to assess fidelity to service delivery models for daily oral PrEP and emerging modalities and measure progress toward enhancing biomedical prevention uptake, persistence, and equitable coverage; and (3) Define universal and modality- specific pre-implementation and implementation activities necessary for settings to integrate emerging prevention options into clinical practice. This project builds on the past work of the investigative team in oral PrEP demonstration and implementation projects, development/testing of novel prevention modalities, and dissemination of evidence-based implementation tools for clinical practice. To accomplish our aims, we will apply two seminal theoretical models from the implementation science literature, and collaborate with seven clinical partners in seven EtHE hotspots across the US, as well as a CDC-funded Capacity Building Assistance (CBA) provider who delivers PrEP training and technical assistance to sites across the country. The knowledge generated by this project will not only advance the field of implementation science, but also create tangible tools that can help clinics, heath systems, and policy decision makers improve PrEP implementation outcomes at a population level. This project has the potential to make a significant and sustained impact on the quality of future implementation efforts, and the speed with which new modalities are effectively disseminated to highest priority populations.

7.1. PROJECT SUMMARY/ABSTRACT -- CORE Project One of the fundamental challenges to effective implementation of HIV prevention interventions is the engagement of clients who are eligible for and would benefit most from them. This Core Project is focused on this critical implementation problem: the need to develop and test novel implementation strategies that increase engagement, uptake, and sustainment of proven HIV prevention interventions, including rapid testing, PrEP/PEP, and iART. Based on a review of the research literature and data collected directly from community members in their EHE high priority jurisdictions, the New York City Health Department (NYC HD) has identified three core determinants of this HIV prevention implementation problem: (1) clients? anticipated and experienced stigma and discrimination limit acceptability and uptake; (2) providers? implicit and explicit bias limit offers and dissemination; and (3) systemic emphasis on siloed services and risk-based eligibility limits access and availability. In response to this problem, the NYC HD has chosen an implementation strategy called the GOALS Approach to Sexual Health, which is designed to: a) universalize and normalize HIV prevention conversations and interventions; and b) disseminate a client-centered, gender-affirming, non-discriminating, anti-stigmatizing and trauma-informed approach to sexual history and HIV prevention conversations. This Core Project uses a two-phase cluster-randomized, stepped-wedge implementation trial to evaluate adoption of the implementation strategy in 20 agencies funded by the NYC HD. Based on an implementation science model, we will examine outcomes at three levels: a) implementation outcomes (e.g., rates of HIV testing, PrEP uptake, immediate linkage of newly diagnosed patients to care); b) service outcomes (e.g., equitable distribution of HIV prevention interventions to highest priority populations); and c) patient outcomes (e.g., impact on city-wide HIV incidence, engagement in care, and viral suppression). Secondary analysis will also be conducted on hypothesized mechanisms (i.e., mediators) as defined in the program?s logic model, including dimensions of provider competence and patients? experience. Model fidelity data will be collected on enactment of the GOALS Approach implementation strategy by the NYC HD, and its ability to successfully implement the strategy at each of the individual agencies. Finally, qualitative data will be collected to assess barriers and facilitators to implementation at both the health department and agency levels to inform future adaptation and dissemination of the implementation strategy. 7.2. PROJECT SUMMARY/ABSTRACT -- COLLABORATIVE Project One of the most persistent challenges in health care provision is quality. It is often easy to determine which or how many services are being provided to clients by a given agency or program, but it is far more difficult to determine how well these services are being delivered, or what aspects of service delivery have the greatest impact on outcomes. This Collaborative Project is based on the scientific premise that quality can be defined, measured, and supported by a re-envisioning of health department contract practices, and that an implementation science approach can evaluate this innovative strategy and identify its strengths and weaknesses for broader dissemination. In this Collaborative Project, we address the persistent problem of quality through: a) an implementation strategy that defines quality in HIV prevention services and operationalizes a logic model through which higher quality services will address known barriers and inequities at the community-, system-, and client-levels; b) a data collection and quality improvement and management (QIM) strategy that focuses on quality and quality metrics as incentive-based deliverables in HIV prevention contracts; c) a training and technical support system that works with agencies to identify challenges to quality service provision and supports them to identify and enact approaches to address those challenges; and d) a collaborative research design that measures initiation, adoption, and sustainment of each component of this implementation strategy, and applies a programmatic logic model to examine the impact of each component on hypothesized determinants, mechanisms, and outcomes. The New York City Health Department (NYC HD) has selected a Quality-Based Financing (QBF) model to fund its HIV prevention contracts (in contrast to a traditional fee-for-service model) as an implementation strategy to decrease inequities in access, utilization, and outcomes for HIV prevention services, and to equitably decrease the HIV incidence among NYC?s highest priority populations. This Collaborative Project has four main objectives: (1) conduct an interrupted time series (ITS) analysis to evaluate the impact of implementing the QBF model; (2) qualitatively explore factors that potentially explain differences in successful implementation of QBF across different agencies; (3) Identify factors significantly associated with differential effectiveness of the QBF model using longitudinal multiple regression analysis; and (4) Measure model fidelity and monitor QBF implementation at the level of the health department and funded agencies.