Jane M. Simoni - US grants

New combination antiretroviral therapies have demonstrated unprecedented efficacy yet require strict adherence to complex dosing regimens to inhibit rapid virus replication and the generation of multi-drug resistant strains. The proposed project for a FIRST TIME R01 is a randomized, controlled intervention to enhance antiretroviral adherence among an inner city group of many current or former injection drug users -- a population at high risk of nonadherence. The study site is Jacobi Medical Center's AIDS Consultation Services in the Bronx, New York, where attending physicians will be working in collaboration with the PI. The intervention involves a peer support or "buddy" system that is practical, inexpensive, does not require extensive training or additional staff, and has the potential for widespread dissemination. Drawing on the social support literature and social learning theory, the intervention is designed to provide affirmational, emotional, spiritual, and informational support to target three key groups of factors that have been empirically demonstrated to affect adherence: self- efficacy, negative affective states, and knowledge of the medication regimen. Clinic staff will employ specific criteria to nominate patients as "buddies." They will undergo a 6-session training and be supervised and supported thereafter in a facilitated support group. The buddies will then be assigned to 75 patient "peers." The buddies will provide social support via thrice weekly phone calls and visits for 3-months in accordance with a protocol explained and rehearsed in their training. Adherence of these patients and 75 patients in a treatment-as-usual control condition from the same clinic population will be assessed with self-reports, 3-day recall telephone interviews at months 2 and 4, and the Medication Event Monitoring System (MEMS). All participants will be administered self-report inventories (assessing demographics and other potential moderators, social support, adherence, as well as the factors purported to relate to adherence) at baseline, at the end of the 3-month intervention, and at a 3-month follow-up. In addition to potentially demonstrating empirically the feasibility and efficacy of a peer support intervention, this study will expand current knowledge about the correlates of adherence in this population. Such knowledge has implications for the design of future interventions and clinical trials, where adequate adherence is necessary to insure the validity and reliability of findings regarding new HIV therapies.

DESCRIPTION (provided by applicant): New combination antiretroviral therapies have demonstrated unprecedented efficacy yet require strict adherence to complex dosing regimens to inhibit rapid virus replication and the generation of multi-drug resistant strains. This proposal for a COMPETING CONTINUATION OF A FIRST TIME R01 is a randomized, controlled intervention to enhance antiretroviral adherence among inner city outpatients at a public hospital clinic in Seattle, WA. The intervention tests the relative efficacy of a "buddy" system and a pager intervention against standard of care in a 2 X 2 factorial design. Both interventions are practical, relatively inexpensive, do not require extensive training or additional staff, and have the potential for easy and widespread dissemination. Conceptually based in the social support literature and social learning theory and supported by findings from the original buddy project and preliminary studies of the pager intervention, the current project is designed to test the effects of providing affirmational, emotional, spiritual, and informational support to target key groups of mediators known to affect adherence: self-efficacy, negative affective states, substance abuse, knowledge of the medication regimen, and remembering doses. The buddy intervention involves clinic staff nominating adherent patients as "buddies" who undergo a brief training and receive regular supervision thereafter. The buddies provide social support to fellow patients in accordance with a protocol explained and rehearsed in their training. The pager intervention employs two-way pagers that prompt participants with descriptions of doses and special instructions and provide information about the medications. Adherence of 240 patients will be assessed with self-reports, pharmacy refills, 3-day recall telephone interviews at months 2 and 4, and the Medication Event Monitoring System (MEMS). All participants will be administered face-to-face interviews (assessing demographics and other potential moderators, social support, adherence, and the proposed mediators) at baseline, at the end of the 3-month intervention, and at a 3-month follow-up. This study will provide useful data on rates and correlates of adherence in this at-risk population, on various adherence assessment methodologies, and on the efficacy of two interventions with high exportability.

DESCRIPTION (provided by applicant): China is facing an HIV/AIDS crisis. Although treatment, including free medication, is increasingly available, reports of nonadherence are already surfacing. Within the current window of opportunity, there is an urgent need for research for the development of adherence enhancement programs, which will bolster the efficacy of the medication regimens and thwart the development and transmission of drug resistant virus. The proposed R34 application in response to PAR-03-078 involves a 3-year developmental project to design and pilot a culturally appropriate, clinical feasible, and generalizable program. This project is a multidisciplinary collaboration among experienced investigators at the University of Washington, expert consultants across the U.S., researchers from China's CDC, and care providers at Ditan Hospital in Beijing. The primary aims of the project are to (1) Conduct qualitative research including in-depth interviews and focus groups with patients, their family and caretakers, and providers to determine common barriers and likely facilitators to antiretroviral adherence, which will further guide intervention development; (2) Design a culturally sensitive and theoretically driven adherence program suitable for the Chinese HIV-Positive population, including development of an intervention manual and training materials; (3) Pilot test the program on 10 patients; and (4) After adjustments based on findings from the pilot, implement a preliminary randomized controlled trial (RCT) of 60 patients with 2 arms (minimal vs. enhanced intervention) to assess feasibility and initial efficacy. Although the exact nature of the intervention will depend upon findings from the qualitative phase of the project, research from studies based in the West as well as preliminary work in country suggest the potential acceptability and usefulness of a comprehensive program involving such components as informational group meetings, one-on-one psycho-educational counseling with nurses, DOT provided by family members, alarm reminders, and peer support.

DESCRIPTION (provided by applicant): The sister cities of El Paso, Texas and Ciudad Juarez, Chihuahua situated on the U.S.-Mexico border face a potential explosion in the HIV epidemic. Although antiretroviral therapy (ART) is increasingly available and accessible, preliminary studies indicate that poor adherence and depressive symptomatology detract from its potential success. There no reports in the literature of empirically supported treatments that specifically target this populations. This application, prepared in response to PAR-07-341: HIV Treatment Adherence Research, proposes a 3-year R34 to adapt culturally and then pilot test an empirically supported cognitive-behavioral therapy program for adherence and symptoms of depression (CBT-AD). Additionally, we will assess the feasibility and efficacy of a novel medication monitoring and reminder system (MedSignals(r)) in the form of an electronic pillbox with monitoring and reminding functions that is available in a Spanish-language version. Preliminary work has demonstrated the need for this type of support and the intervention's effectiveness in a different population. In line with the principles of community-based participatory research, researchers at the University of Washington have partnered with a local AIDS service organization (La Fe) as well as faculty at the University of Texas at El Paso to develop the research and mental health infrastructure in the region and design a sustainable treatment program. Specific aims of the study include, first, conducting formative research to adapt the CBT-AD intervention. This qualitative phase of the project will involve the institution of a community advisory board, focus groups, and key informant interviews, and will adhere to the CDC's Map of Adaptation Process. The second aim is to conduct a 2x2 randomized controlled pilot trial among 60 HIV+ Latino adults with depressive symptomatology and suboptimal adherence, comparing the CBT-AD and/or the electronic pillbox to treatment as usual. Our hypotheses are grounded in a conceptual model proposing that the CBT-AD will improve problem solving ability and decrease depressive symptomatology, which will directly improve biomedical outcomes of HIV-1 RNA viral load and CD4 as well as indirectly improve biomedical outcomes through increased motivation, improved memory, and better medication adherence. The electronic pillbox is hypothesized to directly improve on-time adherence after increasing the salience of environmental cues. The innovation and significance of the project lie in the evaluation of a novel technology and the development of a theoretically grounded mental health and adherence treatment specifically geared toward low-income Latinos. Evaluating and implementing generalizable and sustainable mental health and adherence interventions such as the ones proposed are urgently needed in the region to improve HIV treatment outcomes and thwart the development and transmission of drug resistant virus.

DESCRIPTION (provided by applicant): With the requested Midcareer Investigator Award in Patient-Oriented Research (K24), I plan to (a) mentor a multi-disciplinary and socio-demographically diverse group of graduate students and early career investigators in behavioral aspects of global HIV research and (b) expand my own capabilities to conduct research on international online HIV interventions. I have been consistently productive and successful in obtaining funding for my program of patient-oriented research. Moreover, I have a long history of supporting mentees and helping them secure their own funding, with several currently holding K23 and other awards. However, teaching, clinical, and administrative obligations have limited the time I can commit to mentoring. The award will allow me to further devote my time and resources to mentoring (from 5% to 25% effort for mentoring and 25% for career development and research). Moreover, it would move me closer to my longer term goals of becoming an internationally recognized leader in global HIV and mental health research and developing more systematic and formalized mentoring programs both at the University of Washington and at the national level. The University of Washington (the top-funded public institution in the country) and the Clinical Area in the Department of Psychology (currently ranked #1) provide excellent environments for this award. At the UW, there is a large pool of diverse and well qualified mentees, for whom I have outlined specific plans for selecting, mentoring, and involving in my own active ongoing program of research. Plans include continuing and formalizing individual- and group-based support for a cohort of diverse graduate students from across campus as well as physicians, nurses, and behavioral scientists at the junior faculty level. This support will be integrated with ongoing programs at the College level and through the Institute of Translational Health Sciences (ITHS) and the School of Medicine. A diverse group of collaborators--senior mentors who are esteemed and established researchers in their respective fields--have committed their support to this award. My career development activities will involve intensive training in online technologies for intervention research, language development, and mentorship/leadership training. Planned activities capitalize on existing resources at the UW, including my involvement in an ongoing R25-funded training program for Native American scientists, the Center for AIDS Research's Sociobehavioral and Prevention Core, and ITHS. The newly proposed research involves a 4-phase study of an online counseling intervention targeting men and women newly diagnosed with HIV in Beijing, China. This comprises qualitative formative work, a cross-sectional survey, development of a multi-modular online intervention with social networking capabilities, and a pilot randomized controlled trial of the intervention. PUBLIC HEALTH RELEVANCE: This award will assist in increasing the availability of a diverse group of researchers successfully studying behavioral aspects of HIV, which is crucial to combating this global pandemic. Additionally, it will assist in the career development of a mid-career investigator who aims to develop an online program to assist individuals struggling with a new HIV diagnosis in settings where access to mental health counseling is limited.

DESCRIPTION (provided by applicant): Worldwide, there are over 33 million persons living with HIV/AIDS (PLWHA). One of the main concerns among PLWHA who are parents is whether, when, and how to disclose their diagnosis to their children. In low resource, high-stigma settings like China, parents are desperate for guidance in disclosing yet HIV care providers remain professionally unprepared to intervene. In this R21 application, prepared in response to RFAHD- 12-205 Disclosure of HIV-Status to Children in Low- and Middle-Income Country Settings (R21), we propose to conduct formative work; develop an innovative, culturally appropriate disclosure-support counseling intervention for parents with adolescent children; and pilot test it in Shanghai, China. Facilitated by nurses assisted by HIV+ parent peers, the intervention will likely involve 2-3 sessions over 3 months and be administered at the clinic. Grounded in Murphy's familial disclosure model, it will comprise 3 components: individualized assessment, decision-making and support, and disclosure planning and action. Final content will be determined by the formative work, prior research, and theory on familial disclosure. A low-burden intervention that capitalizes on expanding the nurses' role, the intervention has the potential for widespread implementation to better meet the needs of PLWHA in limited-resource settings. This project is a multidisciplinary collaboration among experts in familial adaptation to HIV and child development as well as behavioral research in China. Public health officials from China and care providers will be involved from Shanghai Public Health Clinical Center (SPHCC) - the proposed study site. The team has decades of combined experience conducting HIV behavioral research in China, with preliminary research pointing to the significance and innovation of this approach and their ability to work collaboratively and successfully with Chinese investigators. The work will leverage funding from the PI's K24 Mid-Career Development Award, during which preliminary qualitative data for the study were collected. Specific aims of the 2-year project are to (1) develop a disclosure support intervention by (1a) forming provider and peer advisory boards, (1b) analyzing qualitative data, and (1c) manualizing the final counseling protocol; and (2) pilot test the disclosure support intervention by (2a) evaluating acceptability and feasibility with a preliminary randomized trial among 20 families with at least one HIV-positive parent and one child 13-17 years of age and (2b) assessing outcomes in parents (quality of life and mental health indicators, adherence, social support, and disclosure stress, efficacy, readiness, and completion); children (behavior, psychological well-being); and families (parent-child relationship, family communication). The intervention will be compared to treatment as usual, with baseline (0 mos.), immediate post-intervention (3 mos.), and 3-month follow-up (6 mos.) assessments. Public Health Relevance: This application proposes to develop a nurse-delivered, peer-assisted intervention targeting parents living with HIV in China. The goal is to assist parents in deciding whether, when, and how to disclose their HIV diagnosis to their children, in order to improve psychological functioning of themselves and their children, management of the parents' HIV disease, and overall family functioning. The intervention will be designed to address the need in low-resource settings, where there are few highly trained mental health professionals.

DESCRIPTION (provided by applicant): With the requested Midcareer Investigator Award in Patient-Oriented Research (K24), I plan to (a) mentor a multi-disciplinary and socio-demographically diverse group of graduate students and early career investigators in behavioral aspects of global HIV research and (b) expand my own capabilities to conduct research on international online HIV interventions. I have been consistently productive and successful in obtaining funding for my program of patient-oriented research. Moreover, I have a long history of supporting mentees and helping them secure their own funding, with several currently holding K23 and other awards. However, teaching, clinical, and administrative obligations have limited the time I can commit to mentoring. The award will allow me to further devote my time and resources to mentoring (from 5% to 25% effort for mentoring and 25% for career development and research). Moreover, it would move me closer to my longer term goals of becoming an internationally recognized leader in global HIV and mental health research and developing more systematic and formalized mentoring programs both at the University of Washington and at the national level. The University of Washington (the top-funded public institution in the country) and the Clinical Area in the Department of Psychology (currently ranked #1) provide excellent environments for this award. At the UW, there is a large pool of diverse and well qualified mentees, for whom I have outlined specific plans for selecting, mentoring, and involving in my own active ongoing program of research. Plans include continuing and formalizing individual- and group-based support for a cohort of diverse graduate students from across campus as well as physicians, nurses, and behavioral scientists at the junior faculty level. This support will be integrated with ongoing programs at the College level and through the Institute of Translational Health Sciences (ITHS) and the School of Medicine. A diverse group of collaborators--senior mentors who are esteemed and established researchers in their respective fields--have committed their support to this award. My career development activities will involve intensive training in online technologies for intervention research, language development, and mentorship/leadership training. Planned activities capitalize on existing resources at the UW, including my involvement in an ongoing R25-funded training program for Native American scientists, the Center for AIDS Research's Sociobehavioral and Prevention Core, and ITHS. The newly proposed research involves a 4-phase study of an online counseling intervention targeting men and women newly diagnosed with HIV in Beijing, China. This comprises qualitative formative work, a cross-sectional survey, development of a multi-modular online intervention with social networking capabilities, and a pilot randomized controlled trial of the intervention.

Abstract Preserving the health of patients living with HIV and achieving an end to the HIV epidemic depend upon expanding ART access and assuring treatment success. In Haiti, the country most heavily impacted by HIV/AIDS in the Caribbean region, use of ART has scaled up dramatically; however, concerning levels of attrition, sub-optimal adherence, and suspected treatment failure have been observed. Building upon preliminary research establishing the validity of an electronic medical record (EMR)?based alert, the proposed research project will develop and pilot test a provider-based intervention using an electronic alert together with brief ART adherence counseling to improve ART adherence and reduce the incidence of ART treatment failure. This innovative intervention leverages the existing nation-wide iSanté EMR system and offers potential for wide-scale impact on care delivery and patient adherence, by targeting scarce personnel and resources toward those most in need. The aims of the project are to: 1) conduct formative research on the potential role of EMR alerts and healthcare providers in ART adherence counseling in Haitian HIV primary care clinics; and 2) conduct a preliminary clinical trial of the iSanté Plus intervention. The research study involving mixed methods will take place in two large public-sector ART clinics in Port-au-Prince, where the multidisciplinary MPI research team has establish relations during a decade of prior collaborations. A formative evaluation phase using mixed methods will examine provider and patient beliefs and attitudes toward the EMR-based alert and provider-based ART adherence counseling. This work will inform the design and development of the iSanté Plus intervention. A pilot study of the feasibility and acceptability of the intervention using a quasi-experimental study design will be carried out in one intervention and one control ART clinic. Outcomes of interest include retention in care, ART adherence, incidence of ART treatment failure by WHO immunologic and clinical criteria (all measured using routine EMR data), and HIV viral suppression (measured using HIV-1 viral load testing in a sub-sample of patients). Patient information, motivation, and behavior will be examined as mediating factors. Approximately 130 Haitian, Creole-speaking patients over age 18 who have recently initiated a first-line ART regimen are expected to be enrolled in the study and to be followed for 9 months. While the study design and sample size will not be powered to measure effectiveness of the intervention, the trial will establish feasibility, acceptability, and study procedures relevant for a larger-scale trial using a cluster randomized or stepped-wedge study design at a national level in Haiti.

Abstract Advances in HIV prevention and treatment such as PrEP, medical male circumcision, and more potent antiretroviral therapies may be primarily biomedical in nature, but they require substantial behavioral considerations for optimal uptake. Moreover, the 2015 White House National HIV/AIDS Strategy specifically identifies screening and treatment of mental health and substance use disorders as critical to reducing disparities, reducing morbidity and mortality associated with HIV, and preventing new HIV infections. Both domestically and globally, mental health has been closely tied to substance use disorders, which impact adherence and retention in care. A combination of behavioral and biomedical expertise, therefore, is required to successfully address the HIV epidemic worldwide, with NIH funding priorities reflecting this need. Emanating from the former Sociobehavioral Prevention Research Core, this newly re-imagined Behavioral Science Core (BSC) consists of diverse, multidisciplinary faculty with relevant expertise in behavioral science who will provide CFAR investigators with critical expertise not currently available locally. The overall goal of the BSC is to catalyze behavioral science research that will contribute to curbing the global HIV epidemic and improve outcomes along the continuum of HIV prevention and care. Specific aims are: 1: Promote and support collaborative, interdisciplinary HIV research that integrates cutting-edge behavioral science by constructing a behavioral science infrastructure within the CFAR that will maintain an online database of CFAR behavioral resources and investigators, organize symposia to promote local and regional cross- disciplinary collaboration, and facilitate coordinated and collaborative responses to relevant funding opportunities; 2: Provide technical assistance related to behavioral science to the diverse community of CFAR investigators, with a particular focus on the development and evaluation of intervention strategies, behavioral theory, and measurement of mental health and substance use; 3: Provide training and assistance in the use of qualitative methods, especially to inform the development and evaluation of behavioral interventions, including a workshop series and a mobile Qualitative Methods Laboratory fully equipped with video- and audio-recording capability for use by CFAR investigators for usability testing, acceptability assessment, cognitive interviewing, focus group sessions, and in-depth qualitative interviews; 4: Provide mentorship, education, and training on behavioral science integration to early- and mid-stage investigators, with a priority on underrepresented racial/ethnic minorities by convening a monthly Junior Investigator Group as well as (in collaboration with Developmental Core) offering consultations for relevant New Investigator Award (NIA) applicants, participating in mock peer reviews, and supporting eligible faculty in applying for training awards and mentoring successfully.

Project Summary In 2017, UNAIDS estimated that 23% of diagnosed persons living with HIV (PLWH) were not accessing antiretroviral therapy (ART), and 18% of PLWH taking ART had unsuppressed viral loads. The development of sustained-release or long-acting injectable antiretroviral therapy (LAI ART) is an important technological advance that could increase ART uptake and adherence by providing new options to support viral load suppression. Research is urgently needed to understand factors that will drive end-user acceptability, so that developers can iteratively formulate more desirable products and funders can identify and prioritize the products most likely to have high uptake and sustained use. This proposal has the following aims: (1) To design and pilot test a discrete choice experiment (DCE) to identify product and delivery attributes related to LAI ART acceptability among patients in the United States (US), based on our prior work and key informant interviews; (2) To recruit 200 ART naïve-individuals and 500 ART-experienced individuals in Seattle and Atlanta for a DCE to estimate LAI ART product preferences and identify patient characteristics associated with acceptability among these two key potential end-user groups; and (3) To design and pilot test a similar DCE instrument for use in Kenya, then recruit 200 ART naïve-individuals and 500 ART-experienced individuals in Nairobi to learn about patient preferences in the region most impacted by the HIV epidemic. Innovations in the proposed research include a focus on novel LAI ART products in development, inclusion of two patient perspectives (i.e., those just starting treatment and those considering a switch), and exploration of how individual characteristics including prior ART adherence and treatment outcomes influence patient preferences. Our multidisciplinary team includes clinical researchers, behavioral scientists, and health economists with expertise in DCE design and modeling from the University of Washington (UW), RTI International, and Emory University in the US, and from Kenyatta National Hospital in Kenya. The proposed work will take place at two AIDS Clinical Trials Group clinical research sites in the US (i.e., the UW AIDS Clinical Trials Unit in Seattle and the Ponce de Leon Center in Atlanta), and at two HIV clinics within Kenyatta National Hospital in Nairobi, which has been a site for collaborative research with the UW?s Kenya Research and Training Program for over 25 years. Supported by preliminary studies conducted as part of an ongoing UM1 project to develop LAI ART (AI120176, Ho/Collier, NIAID Targeted Long-Acting Combination Antiretroviral Therapy), the proposed work will advance LAI ART product development efforts by providing key estimates of acceptability and patient preferences, enabling funders, product developers, and policy makers to optimize products for the greatest likelihood of uptake, adherence, and long-term viral suppression.

The Indigenous people of the Americas experience persistent and dire health disparities related to HIV/AIDS. Despite the glaring disparities, there is a paucity of culturally grounded research addressing their biomedical and socio-behavioral health concerns. A strong network of highly trained Indigenous scholars dedicated to culturally relevant HIV prevention research would contribute to ameliorating HIV-related health disparities among Indigenous people. This competitive renewal application, in response to PAR-17-485: NIMH Research Education Mentoring Program for HIV/AIDS Researchers (R25), proposes a third iteration of the Indigenous HIV/AIDS Research Training Program (IHART). IHART3-Itza will develop a cadre of culturally grounded Native scholars capable of serving as PIs on extramurally funded HIV/AIDS-related prevention and disparities studies with Indigenous populations. The IHART3-Itza program is based on the success of the first 10 years of IHART (IHART and IHART2-Lauhoe), the only Native-specific HIV/AIDS research education mentorship program in the US. IHART3-Itza extends the reach of the original IHART programs from American Indians/Alaska Natives, Native Hawaian/Pacific Islanders, underrepresented racial/ethnic groups, and non-Natives working in Indian Country to include as well the historically underserved Indigenous Latinx Populations (ILP). ILP include people originally or descended from Indigenous communities in Mexico and Central and South America. Whereas IHART2 focused primarily on newly postdoctoral scholars, IHART3-Itza will target more experienced early- stage investigators (5-10 years post-Ph.D.) interested in developing novel expertise in HIV prevention research. Finally, the program will target recruitment of scholars residing in or working in the US HIV hot spot regions of the Southeast and West. IHART3-Itza will continue to employ a successful 360 degree co- mentorship approach with flexibility for program Fellows and Mentors to co-identify HIV training, career development, and cultural needs of the Fellow. To achieve the overall objectives of IHART3-Itza, we will select 15 Fellows (3 per year over 5 years) who will undergo a structured 24-month intensive year-round mentorship program that includes: (a) an annual 2-day Summer Research Institute, 5-day writing retreat, and 3-day Scientific Roundtable and grant writing workshop; (b) other training opportunities (webinars; 4 quarterly seminars; on-site mentor shadowing opportunities; and support for participation in HIV/AIDS training institutes and scientific conferences); (c) statistical, editorial, and technical assistance for developing grant applications and writing manuscripts for publication); (d) seed funding ($22,000 for pilot studies); and (e) network development (via mentor networks and website). By the end of the 24-month program, Fellows will have written a pilot grant application, obtained human subjects approval, designed and implemented a funded pilot study, published HIV/AIDS-related articles, submitted and presented HIV-related conference abstracts to national conferences, and begun to develop an HIV-related NIH grant application.