Using data science to measure the impact of opioid agonist therapy in patients admitted with Staphylococcus aureus bloodstream infections

Abstract: This career development award will provide early career support for investigation of the management of infec- tious diseases in the setting of addiction in hospitals. The award will provide support for the candidate to develop expertise in the following areas: 1) addiction science research; 2) natural language processing; 3) machine learn- ing; 4) professional development; and 5) responsible conduct of research. For this, Dr. Goodman-Meza will be mentored by a multidisciplinary, cross-institutional team with expertise in addiction, infectious diseases, and data science. His primary mentor, Dr. Steve Shoptaw, has an extensive track record in addiction-related research and training of future independent investigators. His co-mentors include Dr. Alex Bui and Dr. Matthew B. Goetz. Dr. Bui is an expert in biomedical data science and heads NIH training programs in this field. Dr. Goetz has broad experience of productive infectious diseases clinical research within the Veterans Health Administration (VHA). The current opioid epidemic in the United States has been associated with an increase in infections, in particular hepatitis C and bacterial infections. Bacterial infections are the leading infectious diagnosis leading to hospitali- zation in individuals with an opioid use disorder (OUD), and incur significant healthcare expenditures. Despite the availability of opioid agonist therapy (OAT) in the form of methadone or buprenorphine, less than 20% of people with OUD actually receive OAT. Hospitalization for a bacterial infection may be an ideal time to initiate OAT, but the benefits of this practice are unknown. In this proposal, the candidate will assess the impact of initiating OAT in people who inject opioids admitted to the VHA due to a Staphylococcus aureus blood stream infection (bacteremia) – the most common bacterial pathogen among people who inject opioids. Using data already collected for 36,868 cases of S. aureus bacteremia (SAB) from the VHA electronic data repository, the candidate will address three research questions: 1) is a natural language processing algorithm (NLP) more ac- curate than a standard International Classification of Diseases (ICD) code-based approach at screening records to correctly identify individuals who inject opioids in a cohort of patients admitted with SAB; 2) what are the temporal and geographic trends of SAB in people who inject opioids and those who receive OAT at the facility- level; and 3) using a machine learning framework, what are the estimated impacts of OAT on patient centered outcomes – death, readmissions, leaving against medical advice, and subsequent outpatient engagement in OAT. These formative data will help the candidate to establish a productive early career as a physician-scientist and advise development of an OAT-delivery strategy to mitigate infectious complications of injection opioid use. Through this award, Dr. Goodman-Meza will establish himself as an expert physician-scientist at the intersection of infectious disease and addiction, poised to make significant contributions to this important area of medicine.

Project Number: 1K08DA048163-01

https://reporter.nih.gov/search/l7oGElned0OBY3RvfOgPgQ/project-details/9721752

 

Contact PI/ Project Leader

GOODMAN, DAVID, Doctor (dgoodman@mednet.ucla.edu)

 

Organization

UNIVERSITY OF CALIFORNIA LOS ANGELES

 

PUBLIC HEALTH RELEVANCE: Serious, life-threatening bacterial infections in people who inject drugs are increasing with the current national opioid epidemic. Hospitalization of people who use opioids for treatment of infectious complications may be an ideal time to initiate opioid agonist therapy (OAT), an evidence-based practice that has been historically underuti- lized. This project will use innovative data science methods to estimate the impact of initiating OAT in the hospital for patients with a history of opioid injection admitted for treatment of blood stream infections caused by Staph- ylococcus aureus in the Veterans Health Administration.

 

 

Project Start Date: 15-June-2019

Project End Date: 31-May-2024

Budget Start Date: 15-June-2019

Budget End Date: 31-May-2020

 

NIH Categorical Spending

Funding IC:  NATIONAL INSTITUTE ON DRUG ABUSE/ FY Total Cost by IC: $203,040

NIDA Clinical Trials Network: Big South/West Node

Abstract: The Big South/West Node of the NIDA Clinical Trials Network (CTN) represents an expansion of the Texas Node that has been a part of the CTN since 2005. With this expansion, the node will now be guided by the shared leadership of Madhukar H. Trivedi, MD of University of Texas Southwestern Medical Center (UTSW) Steven Shoptaw, PhD of UCLA, and Jennifer S. Potter, PhD, MPH, of UT Health Science Center at San Antonio (UTHSCSA). This fourth competing renewal application builds on our successful track record of leading CTN trials, being good network partners by providing excellent sites for multi-site studies, high productivity in publishing, and training the next generation of scientists. During the 2015-2020 funding cycle, our team developed and led: the largest pharmacotherapy trial for the treatment of methamphetamine use disorder to date (extended-release naltrexone plus high-dose bupropion; CTN0068 ADAPT-2), an in-depth study of the causes of death in a cohort of people living with HIV/HCV and substance use disorder (CTN0064A1), and an implementation study to develop and deploy universal screening for opioid use disorder and measurement based care using buprenorphine (CTN0090 MBC4OUD). Finally, a study testing transcranial magnetic stimulation (TMS) as a treatment for stimulant use disorder has been approved for development, in collaboration with the Southern Consortium Node (CTN0108). For this renewal application, we capitalize on the experience of the Multiple PIs, who collectively have expertise in the treatment of stimulants, the treatment of and public health response to the opioid crisis, and the treatment and care of HIV. Additional investigators bring content expertise spanning addiction science and clinical care, translational science, dissemination and implementation science, informatics, and trial implementation. The expanded Big South/West Node is named to denote the importance of including geographic regions in the South that have historically not been represented within the CTN (i.e., Arkansas, Oklahoma, Louisiana). This geographical expansion provides greater access to diverse patient populations (e.g., diverse racial and ethnic groups; underinsured; underserved; native [American Indian] and immigrant groups) within diverse settings (e.g., rural, urban). Our existing partnerships with primary care networks, large health care systems, and use of electronic health records (EHR) to positively impact substance use, has been further broadened to include multiple statewide networks and resources in new partner states. Our research agenda includes a focus on the fourth wave of the opioid epidemic, building upon the expertise of our investigators in treating stimulant and opioid use disorders, and the changing needs of the regions we serve. Our team has experience with innovative study designs that target all areas of the translational science continuum, and equip our Node to successfully and significantly improve the care of persons who misuse substances.

Project Number:2UG1DA020024-16

https://reporter.nih.gov/search/qtTbPx5VBkmjMkHnI3pnDQ/project-details/10057104

 

Contact PI/ Project Leader

SHOPTAW, STEVEN J, PROFESSOR (sshoptaw@mednet.ucla.edu)

 

Organization

UT SOUTHWESTERN MEDICAL CENTER

 

PUBLIC HEALTH RELEVANCE: Substance use, particularly the use of stimulants and opioids in the fourth wave of the opioid epidemic, are a major public health problem. Research is needed to develop new substance use disorder treatments and to determine how to best broadly disseminate the treatments that are currently available and effective. The National Institute on Drug Abuse’s National Drug Abuse Treatment Clinical Trials Network (CTN) and the Big South/West Node will contribute their expertise to solving the substance use problems impacting our Southern region as well as nationally.

 

 

Project Start Date: 01-September-2005

Project End Date: 28-February-2025

Budget Start Date: 01-June-2020

Budget End Date: 28-February-2021

 

NIH Categorical Spending

Funding IC:  NATIONAL INSTITUTE ON DRUG ABUSE/ FY Total Cost by IC: $4,398,040

Resiliency Education to Reduce Depression Disparities

Abstract: Depression is the leading cause of adult disability and common among lesbian, gay, bisexual (LGB) adults. Primary care depression quality improvement (QI) programs can improve outcomes for minorities more significantly than for nonminorities, but they are seldom available in safety-net systems. We build on findings from Community Partners in Care (CPIC) and Building Resiliency and Increasing Community Hope (B-RICH). CPIC compared depression QI approaches across healthcare and social /community services in communities of color. CPIC included healthcare and “community-trusted” programs (e.g., homeless, faithbased) to work as a network to address depression, compared to individual-program technical assistance. In CPIC, both conditions improved mental wellness, mental health quality of life, and depression over 12 months. B-RICH, a randomized study, evaluated lay delivery of a seven-session, CBTinformed resiliency education class versus case management on patients’ depressive symptoms over three months, in unpublished but completed analyses. The proposed demonstration supplements the resiliency class with a mobile/interactive voice response case management tool to reinforce class content and depression care reminders (BRICH+).

 

Multilevel Integration Strategies to Enhance Service Provider Networks in Vietnam

Abstract: Globally, organizational and system interventions are needed to provide integrated services to address the needs of people living with HIV who use drugs (PLHWUD), including other comorbid conditions. Community health and service workforce can be mobilized to promote service integration, which is particularly critical in low- and middle-income countries. We develop and pilot test multilevel integration strategies in Vietnam, including structural changes for better treatment coordination, strengthening treatment provider networks for improved service collaboration, and involving community health workers to support those in need throughout the treatment cascade. The study is conducted in six provinces in Vietnam. In Phase 1, we conduct formative studies with 20 PLHWUD, 24 clinic providers from HIV and drug use treatment facilities, and six directors of Provincial AIDS Centers. Based on the findings, we establish a provincial coordination team at each participating province. In Phase 2, we implement and pilot test an agency-level intervention by training 72 service providers working at various HIV and drug treatment centers to enhance the coordination and networking among the providers and to improve interactions with their patients. Agency-level aggregated data are collected and compared at the baseline and at 12-months after the intervention. In Phase 3, we implement and pilot test our intervention strategies that focus on community health workers working at commune health centers to enhance their networking and collaboration with clinic providers at the treatment facilities. The intervention focuses on improving their communication skills to outreach and motivates PLHWUD living in the community to link them to and support them to stay in care. To assess intervention outcomes, we will recruit 80 commune health workers (CHW) and 240 PLHWUD from 40 commune health centers (CHC). Intervention outcomes on PLHWUD and CHW will be compared at baseline and every three months for one year.

 

Project Number: R01DA041008(2017)

https://reporter.nih.gov/search/1nF2mB6R7E6QQoc1W9IG1A/project-details/9276658

 

 

Contact PI/ Project Leader

LI, LI, (lililili@ucla.edu)

 

 

Organization

UNIVERSITY OF CALIFORNIA LOS ANGELES

 

 

PUBLIC HEALTH RELEVANCE: There is an urgent need to provide integrated services for People Living with HIV who use drugs (PLHWUD). This study addresses the need by developing and implementing multilevel strategies focusing on strengthening provider networks and partnerships between HIV and drug treatment clinics, as well as between treatment agencies and community health centers. Study findings are expected to inform global efforts in service integration, as enhancing community capacity and partnerships are likely to be a relevant and sustainable strategy in other low- and middle-income countries.

 

 

FOA:  RFA-DA-15-013Study Section: ZDA1-HXO-H(10)R

 

 

Project Start Date:30-September-2015

Project End Date: 31-May-2020

Budget Start Date: 01-June-2017

Budget End Date: 31-May-2018

 

 

NIH Categorical Spending

Funding IC: NATIONAL INSTITUTE ON DRUG ABUSE / FY Total Cost by IC: $501,180

A Comprehensive Community-Based Strategy to Optimize the HIV Prevention and Treatment Continuum for Youth at HIV Risk, Acutely Infected and With Established HIV Infection

Abstract: America’s increasing HIV epidemic among youth aged 12-24 and our concurrent failure to identify, link to care, and achieve viral suppression among youth living with HIV (YLH) suggests the need to identify novel community-based strategies to leverage gateways and settings where high risk and infected youth can be engaged in HIV prevention and treatment. Scientific successes reducing HIV viral reservoirs among acutely infected infants, stopping HIV transmission from HIV-infected adults with undetectable viral loads, and documenting the efficacy of Treatment as Prevention (TASP) suggest strategies to reduce the trend of increasing adolescent HIV infections. This U19 will evaluate the usefulness of these advances for youth aged 12-24 at the highest risk of acquiring HIV- gay, bisexual, transgender youth (GBTY) and homeless youth (HY) – as well as youth living with HIV (YLH) in two HIV epicenters (Los Angeles and New Orleans). All GBTY and HY at five gay-identified community-based organizations (CBO) and homeless shelters will be screened over 18 months. From these screenings, a cohort of 220 YLH and 1,500 highest risk seronegative GBTY and HY will be formed. Over 24 months, this cohort will be repeatedly tested at four month intervals for sexually transmitted infections (STI) and serious drug use, and with 4th Gen HIV tests if seronegative, in order to identify acutely infected youth, engage youth in medical care, and monitor outcomes. Youth are triaged to: Study 1: Acute infection. Using 60 ARV-naive YLH with established infection as controls, we expect to identify 36 YLH with acute infection. All youth with acute infections will be aggressively treated with at least four highly potent antiretroviral therapies (ARV) and repeatedly assessed to examine if prolonged viral suppression is achieved, with reduced viral reservoirs to potentially allow ARV- free HIV remission. Study 2: Stepped care for YLH. Adapting strategies to manage chronic illnesses, we will conduct a RCT comparing a Standard Care Arm (repeated assessments every four month and an Automated Messaging and Monitoring Intervention [AMMI]) to Stepped Care. In the Stepped Care Arm, increasingly more intense interventions are delivered if viral load is detectable: a) the Standard Care Arm; b) an AMMI that is tailored to comorbidities of the specific YLH; or c) a Coach to support during crises, make treatment referrals, and brief interventions. Dried blood spots will monitor viral load and, on a small sample, ARV adherence over time. Study 3: Engaging seronegative youth in the HIV Prevention Continuum. Youth will be randomized to either: a) an AMMI Arm; b) Peer-Support plus AMMI Arm; c) eNavigator and an AMMI arm; or d) Peer-Support plus eNavigator plus AMMI Arm. Each condition aims to optimize the HIV Prevention Continuum. An interdisciplinary team of basic, clinical, and applied researchers with expertise in HIV, STI, behavioral interventions, biomedical interventions, CURE research, perinatal HIV, and a history of participating and coordinating multi-site RCT is participating on this U19 from six universities.

 

Project Number: 5U19HD089886-02

https://reporter.nih.gov/search/HbqgtLEtKUG1ysdAGWkuMQ/project-details/9353195

 

 

Contact PI/ Project Leader

ROTHERAM-BORUS, MARY JANE, PROFESSOR (ROTHERAM@UCLA.EDU)

 

 

Organization

UNIVERSITY OF CALIFORNIA LOS ANGELES

 

 

PUBLIC HEALTH RELEVANCE: Project Narrative HIV among youth has doubled in the last 15 years, with incidence expected to increase 39% by 2020. If acutely infected youth can be identified and treated during the period when their infectivity to others is 5-to 10-fold, we can reduce this expected rise as well as improve youth’s long-term health, reflected in smaller viral reservoirs. The set of studies in this U19 tests a comprehensive set of strategies for acutely infected youth, youth with established infection, and seronegative youth at highest risk of acquiring and transmitting HIV –with policy implications for communities and the Centers for Disease Control and Prevention.

 

 

FOA:  RFA-HD-16-035Study Section: ZHD1-DSR-N(50)1

 

Project Start Date:30-September-2016

Project End Date: 31-May-2021

Budget Start Date: 01-June-2017

Budget End Date: 31-May-2018

 

 

NIH Categorical Spending

Funding IC: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT/ FY Total Cost by IC: $3,738,607

Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO)

Abstract: In response to RFA-DA-17-019 we propose to establish a Coordinating Center for the NIDA Cohorts entitled “C3NPO” to manage and stimulate use of the data generated to address high priority research on HIV/AIDS in the context of substance abuse. Our focus is cutting-edge science powered by the cohorts’ combined sample size of approximately 12,500 participants. We bring together a team of researchers with global leadership in substance use, HIV prevention, clinical science and co-morbidities, immunology, modeling, and bioethics to work with NIDA program scientists to stimulate the highest impact science across NIDA-funded cohorts that have compiled unique repositories of varied and rich data. Our proposal uniquely combines academic and professional research management expertise that will stimulate, manage, and support scientific collaboration. We will enable internal and external investigators to cultivate the data from these cohorts in new and innovative scientific directions. Our bioinformatics capacity is uniquely strong in the area of specimen management, having developed the industry gold standard software that will greatly facilitate sharing of specimens across the cohorts. Our leadership bridges NIDA’s interests with the perspectives and concerns of the cohorts by having a cohort PI/research scientist (Pamina Gorbach, University of California, Los Angeles) partnered with an experienced HIV network bioinformatics management leader (Suzanne Siminski, Frontier Science & Technology Research Foundation (FSTRF). We will leverage other funded research initiatives though our External Scientific Advisory Board (ESAB) such as NIDA-supported efforts to harmonize measures for substance use research and combine that with data linking strategies. We have the endorsement of all cohort PIs that Consortium leadership is best led from another cohort PI to enhance team science and support for our team as the leaders. The collaborative character of this proposing team offers the potential for new developments in bioinformatics techniques that allow integration of diverse and ever more massive sets of behavioral, clinical, and laboratory data for use by cohort and outside researchers. Thus, our proposal will address NIDA’s 2016-2020 Strategic Plan priority focus areas and cross-cutting themes (https://www.drugabuse.gov/about-nida/2016-2020-nida-strategic-plan) by leveraging technology, driving innovation, promoting collaboration, and encouraging data and resource sharing. The strategy will develop infrastructure that allows cross-disciplinary, large-scale analyses leading to the highest impact HIV science on substance use.

 

Project Number: 1U24DA044554-01

https://reporter.nih.gov/search/92PpxIlw3kOeKuNh6d751Q/project-details/9386691

 

 

Contact PI/ Project Leader

GORBACH, PAMINA MAE , PROFESSOR (PGORBACH@UCLA.EDU)

SIMINSKI, SUZANNE

 

 

Organization

UNIVERSITY OF CALIFORNIA LOS ANGELES

 

 

PUBLIC HEALTH RELEVANCE: Our U24 “Collaborating Consortium of Cohorts Producing NIDA Opportunities” (C3NPO) proposal brings together a team of researchers with global leadership in substance use, HIV prevention, clinical science and co-morbidities, immunology, modeling, bioethics, and bioinformatics to work with NIDA program scientists and stimulate the highest impact science across NIDA-funded HIV cohorts. The collaborative character of this proposing team offers the potential for new developments in bioinformatics techniques that allow integration of diverse and ever more massive sets of behavioral, clinical, and laboratory data for use by cohort and outside researchers. Thus, our proposal will address NIDA’s 2016-2020 Strategic Plan priority focus areas and cross- cutting themes by leveraging technology, driving innovation, promoting collaboration, and encouraging data and resource sharing.

 

 

 

Project Start Date: 01-May-2017

Project End Date: 31-March-2022

Budget Start Date: 01-May-2017

Budget End Date: 31-March-2018

 

 

NIH Categorical Spending

Funding IC: NATIONAL INSTITUTE ON DRUG ABUSE  / FY Total Cost by IC: $999,893

HIV Testing, Linkage, and Retention in Care: Contextual Factors and Disparities

Abstract: The purpose of this study is to determine if associations exist between the contexts in which people obtain healthcare (i.e., healthcare context) or live (i.e., residential context) and each of five outcomes (HIV testing, receipt of test results, linkage to HIV/AIDS care, retention in HIV care and HIV viral load). The epidemiology of HIV/AIDS among racial/ethnic minorities (specifically, Blacks and Latinos) and older adults (i.e., 50 and older) suggests they may encounter barriers that contribute to disparities in early detection of HIV and in their prognoses. Hence, we will also examine disparities in the outcomes by race/ethnicity and older age (age >50). Drawing on the sociobehavioral sciences, the study will inform clinical practice in ways that promote equity in care across diverse groups, neighborhood conditions and stages of adulthood. The study’s primary Specific Aims are to: (1) Examine relations between healthcare context, residential context and HIV testing during primary care visits using logistic regression multilevel models with random effects based on primary care patients’ electronic medical records; and, (2) Examine relations between healthcare context, residential context and receipt of HIV test results and linkage to HIV/AIDS care, respectively, among managed care enrollees newly diagnosed as HIV-positive using multilevel logistic regression and Cox proportional hazards models with random effects. The secondary Specific Aim is to determine if racial/ethnic- or age-related (i.e., aged <50 vs. >50 years) disparities exist in these relationships. Building on our work on HIV testing and care, and guided by a model integrating the Public Health Critical Race Praxis and Behavioral Model of Healthcare Utilization, the four-year study based on the electronic medical records (EMRs) of adults enrolled in the largest managed care organization in the region. We will pool data over five years (2007-2011) to examine HIV testing among all patients presenting for primary care, and to examine receipt of HIV test results, linkage to and retention in HIV/AIDS care as well as HIV viral load among all patients newly diagnosed as HIV-positive. The study will comprise four multilevel analyses of patients’ residential contexts (e.g., neighborhood HIV prevalence) and healthcare contexts (e.g., characteristics of the patient population) relative to HIV testing during primary care visits (Aim 1), receipt of HIV test results and linkage to HIV/AIDS care among those diagnosed as HIV-positive (Aim 2), retention in HIV/AIDS care and HIV RNA viral load up to one-year post diagnosis. We will use personal and geospatial codes in the EMRs to link to: (1) files containing detailed information on each provider (e.g., demographics, specialty); (2) public data from the Centers for Disease Control and Prevention on HIV prevalence and HIV test sites in each zip code; (3) 2010 Census socioeconomic data (e.g., concentrated poverty) for each zip code; and, (4) global positioning system software to calculate the distance from a patient’s home to their provider. This interdisciplinary, inter- institutional collaboration leverages the expertise of a diverse team of new and seasoned investigators.

 

Project Number: 5R01NR014789-04

https://reporter.nih.gov/search/IbMfJxDXuUq2-aD5SULsNw/project-details/9215532

 

 

Contact PI/ Project Leader

FORD, CHANDRA L , POSTDOCTORAL SCHOLAR (clford@ucla.edu)

 

 

Organization

UNIVERSITY OF CALIFORNIA LOS ANGELES

 

 

PUBLIC HEALTH RELEVANCE: The goal of the proposed research is to learn why adults, especially racial/ethnic minorities and older adults, who have insurance may nevertheless not receive HIV testing or HIV/AIDS care at the recommended levels. The study compares MCO enrollees based on their medical records, assigned providers and neighborhood social conditions to see if certain patients have a harder time getting testing or care because of the type of provider they see or because of where they live.

 

 

 

Project Start Date: 10-April-2014

Project End Date: 28-February-2019

Budget Start Date: 01-March-2017

Budget End Date: 28-February-2019

 

 

NIH Categorical Spending

Funding IC: NATIONAL INSTITUTE OF NURSING RESEARCH  / FY Total Cost by IC: $371,958

STI Screening as a Combined HIV Prevention Platform for MSM in Peru

Abstract: Periodic counseling, testing, and treatment for rectal sexually transmitted infections (STIs) provides a multi- dimensional platform to integrate behavioral and biological HIV prevention strategies for men who have sex with men (MSM) in Peru. Rectal STIs like gonorrhea and chlamydia are key risk factors for HIV acquisition among MSM, both as indirect behavioral markers of recent unprotected receptive anal intercourse (URAI), and as inflammatory factors that increase cellular risk for HIV co-transmission. However, there have been no prospective studies of interventions addressing the specific behavioral and biological risk factors associated with rectal STI transmission or the potential impact on HIV transmission risk of integrating rectal GC/CT screening with other prevention services. We will use nucleic acid testing to screen 750 behaviorally high-risk MSM for rectal gonorrheal and/or chlamydial (GC/CT) infection. GC/CT-positive subjects will receive single-dose antibiotic treatment and either single-session Personal Cognitive Counseling (PCC) (n=50) or standard post-test counseling (n=50). A GC/CT-negative control group (n=50) will also be enrolled to compare biological outcomes including changes in levels of inflammatory cytokines following rectal STI. Aim 1: To adapt a Personalized Cognitive Counseling (PCC) model for use with MSM in Peru. Aim 2: To adapt and pre-test the SJEI and behavioral assessment instruments for use with MSM in Peru. Aim 3: To pilot a combined HIV prevention intervention based on rectal STI counseling, testing, and treatment for MSM in Peru. Estimates of feasibility/acceptability of the intervention, GC/CT prevalence/re-infection rate and the effect on behavioral and biological mediators of HIV infection will be used to plan an R01 evaluation of rectal STI surveillance as HIV prevention for MSM in Peru.

Project Number: 5R01MH105272-03

Mechanisms of Cardiac Dysfunction in HIV and the Effect of Statins

Abstract: Contemporary cohorts of people living with HIV (PLWH) have a ~ 2.5-fold increased relative risk of heart failure versus matched controls. The predominant type of heart failure among PLWH is heart failure with a preserved ejection fraction (HFpEF). This type of heart failure is typically preceded by diastolic dysfunction, a condition in which the left ventricle of the heart stiffens, resulting in delayed relaxation and increased filling pressures. Among PLWH, the prevalence of diastolic dysfunction is strikingly high: 43%. Once diastolic dysfunction has progressed to overt HFpEF, no good therapeutic options exist. Thus, strong imperatives exist to test rational, safe strategies which may preserve diastolic function and prevent progression to overt heart failure among aging PLWH on ART. There are two key processes which likely contribute to the development of diastolic dysfunction in HIV. The first is myocardial fibrosis, a condition in which excess collagen is deposited in the myocardial structural space. The second is myocardial steatosis, a condition in which triglycerides are ectopically deposited within cardiomyocytes. Myocardial fibrosis and myocardial steatosis are both increased among PLWH, in relation to diastolic dysfunction. We postulate that PLWH without overt heart failure, statin therapy will reduce the progression of myocardial fibrosis and myocardial steatosis, preserving cardiac function. Our primary hypothesis is that statin effects to dampen systemic immune activation and inflammation will translate to reduced in situ myocardial inflammation and, in turn, reduced myocardial fibrosis. We will also test an alternate hypothesis that statin effects to improve lipid metabolism will result in reduced ectopic fat deposition in the heart. Cardiac magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) represents a gold-standard approach with which to test our hypotheses. We propose an observational cardiac MRI/MRS-based study, CARDIAC-MR, integrated with an ongoing randomized trial of pitavastatin vs. placebo (REPRIEVE). From 8 REPRIEVE sites, we will co-enroll 130 PLWH aged 40-75 without known heart failure. Outside of REPRIEVE, we will orchestrate additional study visits at entry and 24 months. At these visits, participants will undergo cardiac MRI/MRS, as well as targeted metabolic and immune phenotyping. Our work will answer scientific questions relevant to heart failure prevention in HIV which will not otherwise be addressed in REPRIEVE. If we confirm our hypothesis that statins forestall progression of myocardial fibrosis and/or fat among PLWH, we will have found the first effective strategy to preserve cardiac function in HIV. Even in the case of null statin effects on fibrosis/fat, our baseline characterization of pathologic pathways predisposing to cardiac dysfunction will help identify future targeted strategies geared toward heart failure prevention in HIV. Given that heart failure is a highly morbid, age-related comorbidity to which PLWH are particularly vulnerable, our work will have significant clinical implications to improve the lives of at-risk individuals aging with HIV.

 

Project Number: 1R01HL137562-01A1

https://reporter.nih.gov/search/lk4QlpSW3k6NH9JxPR4g4Q/project-details/9409760

 

 

Contact PI/ Project Leader

NEILAN, TOMAS G, ASSISTANT PROFESSOR (tneilan@partners.org)

 

 

Organization

MASSACHUSETTS GENERAL HOSPITAL

 

 

PUBLIC HEALTH RELEVANCE: Individuals living with HIV have higher rates of heart failure than individuals without. We will identify why individuals living with HIV develop heart failure and test whether statins, a type of drug typically used to lower cholesterol, can protect the heart muscle and improve the way the heart functions among individuals with HIV.

 

 

Project Start Date: 01-July-2017

Project End Date:31-March-2021

Budget Start Date: 01-July-2017

Budget End Date: 31-March-2018

 

 

NIH Categorical Spending

Funding IC: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE/ FY Total Cost by IC: $708,470

Siempre Seguire: A Pilot Intervention to Improve Coping With Discrimination and Adherence Among HIV-Positive Latino MSM

Abstract: HIV-related disparities in diagnosis and disease outcomes persist among Latinos, and Latinos living with HIV show a lower percentage of viral suppression compared to the general HIV-positive population. A growing body of work suggests that stigma and discrimination contribute to health disparities, especially among people living with HIV, who may experience discrimination due to multiple stigmatized identities related to HIV- serostatus, race/ethnicity, and sexual orientation. Internalized stigma and discrimination may lead to health- related disparities by increasing detrimental physiological stress responses, resulting in maladaptive coping and poor health behaviors, including non-adherence to treatment. Moreover, the chronic stress of discrimination may weaken immune function, leading to worse HIV outcomes, including increased HIV viral load. In the proposed research, we will integrate adherence skills-building strategies into a recently developed intervention, Siempre Seguiré, a 7-session group cognitive behavioral therapy (CBT) intervention for HIV- positive Latino men who have sex with men (LMSM) that aims to improve adaptive coping responses to discrimination. In a small pilot of 30 participants, the intervention was associated with improved coping at follow-up as compared to baseline. However, this pilot did not include a control group, did not address or examine HIV-related behaviors and outcomes such as adherence, retention in care, and viral load suppression, and had a very low sample size. Thus, in the proposed research, we will conduct a larger pilot study in which preliminary effects on HIV outcomes can be assessed. The specific aims are: (1) To modify and refine Siempre Seguiré, a newly developed culturally congruent CBT group intervention for HIV-positive LMSM, to include strategies for antiretroviral treatment adherence and retention in HIV care; and (2) To conduct a small randomized pilot of Siempre Seguiré to examine feasibility and acceptability, as well as to explore preliminary effects on: (a) coping responses to discrimination; and (b) antiretroviral treatment adherence, viral load suppression, and HIV care retention, among LMSM living with HIV. In Phase 1, we will work with HIV treatment adherence intervention experts and key stakeholders, including a community advisory board, to refine our pilot intervention as needed and update our manual to integrate information and skills building regarding HIV treatment adherence and retention in care. In Phase 2, we will conduct a small randomized controlled trial of 80 participants (40 intervention participants divided evenly over 4 intervention groups vs. 40 wait-list control participants). To our knowledge, our study will be the first to test an intervention that addresses coping with discrimination from multiple identities. Our proposed research is consistent with the Institute of Medicine report, The Health of Lesbian, Gay, Bisexual, and Transgender People, which recommends developing interventions to address racial disparities and mental health effects of discrimination among sexual minorities.

 

Project Number:  1R34MH113413-01A1

https://reporter.nih.gov/search/NfaaiDsLWUizEGUyXRmd4w/project-details/9407123

 

 

Contact PI/ Project Leader

BOGART, LAURA M, SENIOR BEHAVIORAL SCIENTIST (LBOGART@RAND.ORG)

 

 

Organization

RAND CORPORATION

 

 

PUBLIC HEALTH RELEVANCE:  Latinos in the U.S., especially those who are men who have sex with men, show HIV-related disparities, tending to be diagnosed at a later disease stage, leading to delays in care entry and antiretroviral treatment use, and lower rates of viral suppression. No culturally congruent interventions have been developed to address stress resulting from discrimination, a key contributor to disparities in HIV outcomes among Latino men who have sex with men. We propose to integrate adherence skills-building into a recently developed intervention that addresses coping with discrimination among Latino men who have sex with men.

 

 

Project Start Date:01-August-2017

Project End Date: 31-May-2020

Budget Start Date: 01-August-2017

Budget End Date: 31-May-2018

 

 

NIH Categorical Spending

Funding IC: NATIONAL INSTITUTE OF MENTAL HEALTH/ FY Total Cost by IC: $194,834