Steven P. Woods, Psy.D. - US grants

DESCRIPTION (provided by applicant): Despite considerable scientific progress over the past 15 years, notable limitations persist in the theoretical and clinical significance of memory assessment in persons with HIV-1 infection. The overarching aim of this revised multidisciplinary project is to provide a conceptually-driven approach to delineating the impact of HIV-1 infection on prospective memory (ProM). ProM is a unique aspect of episodic memory sensitive to fronto-striatal damage that encompasses the complex processes of forming, monitoring, and executing future intentions vis-a-vis ongoing distractions. Consideration of ProM can enhance prediction of- and interventions related to - instrumental activities of daily living (lADLs). It is therefore surprising that ProM has not been evaluated in HIV-1, especially given the fronto-striatal neuropathogenesis of HIV-1-associated memory deficits and their impact on lADLs. Accordingly, this revised research application is guided by the following specific aims: 1) to clarify the nature, extent, and disease correlates of ProM impairment in HIV-1 infection; 2) to delineate the cognitive mechanisms of ProM impairment in HIV-1 using both clinical and experimental measures; and 3) to assess the efficacy of ProM in predicting lADLs (e.g., medication adherence) in HIV-1. We will recruit 200 HIV+ participants and 50 demographically comparable controls to evaluate the following primary hypotheses: 1) HIV-1 infection is associated with deficient executive control of encoding and retrieval within ProM; 2) ProM impairment is associated with advanced HIV-1 disease (e.g., viral load); and 3) ProM provides incremental validity relative to traditional cognitive tests in predicting lADLs, including medication adherence. This study promises to produce important conceptual and practical innovations regarding the nature and clinical assessment of HIV-associated cognitive disorders, and may ultimately facilitate the development of ProM-based interventions to minimize the impact of cognitive disorders on persons with HIV-1 infection, caregivers, and the health care system.

DESCRIPTION (provided by applicant): Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN) Interdisciplinary clinical research on the combined effects of substance abuse and HIV infection on brain structure and function is of considerable relevance to public health initiatives. However, there are presently very few laboratories conducting such research and no current training programs dedicated to preparing the next generation of investigators in clinical research at the intersection of addictions and neuroAIDS. Accordingly, we propose to establish a new Ruth L. Kirschstein National Research Service Award Institutional Training Grant (NRSA T32) entitled, Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN). The aim of TRAIN is to prepare a steady state of four pre-doctoral students and two post-doctoral fellows in clinical neuropsychology for multidisciplinary academic careers focused on the central nervous system (CNS) effects of substance abuse and HIV infection. We will recruit a highly qualified and culturally diverse cohort of trainees that demonstrate promise toward achieving productive academic careers. The TRAIN program will emphasize research training in three primary, interrelated CNS outcomes, which were selected because of their salience and public health relevance as clinical features of HIV-infected substance abusers: (1) neurocognitive impairment (e.g., decision-making, memory); (2) everyday functioning (e.g., medication adherence, vocational outcomes); and (3) structural and functional neuroimaging (e.g., diffusion tensor imaging). Students and fellows will be actively engaged in individualized, flexible career development plans that will include applied research training, didactics (e.g., formal class work and structured seminars), and targeted clinical experiences. An accomplished faculty with strong training interests and a long history of collaborative research will be available to mentor the trainees. The TRAIN faculty consists of 20 mentors across multiple academic disciplines that possess considerable expertise in neural injury, neuroimaging, neuropsychology, and everyday functioning in substance abuse and HIV infection. TRAIN will be led by Dr. Steven Paul Woods and Co-Directors, Drs. Igor Grant and Robert K. Heaton, who will oversee all of the training, scientific, and administrative aspects of the program, including a rigorous process of internal and external evaluation. The TRAIN program will be housed within the Department of Psychiatry at the University of California, San Diego, where it will benefit from a resource rich academic environment that includes a strong substance abuse and neuroAIDS research infrastructure, most notably the NIDA-funded Translational Methamphetamine AIDS Research Center (TMARC). In summary, TRAIN will bring together a bright and diverse cohort of pre- and post-doctoral trainees, an accomplished multidisciplinary team of mentors, an effective administrative structure, and broad array of academic resources to prepare the Nation's next generation of academics who will advance the science and practice of substance abuse and neuroAIDS.

DESCRIPTION (provided by applicant): HIV-associated neurocognitive disorders (HAND) are common in the era of combined antiretroviral therapy (ART) and are a significant burden on public health resources. Yet current standard-of-practice methods for screening and ascertaining the everyday functioning impact of HAND are generally insensitive, outdated, and/or highly impractical for routine use in clinic, which may adversely affect health outcomes by leaving many individuals with syndromic HAND undiagnosed and untreated. Advances in Internet technology may provide an especially germane, naturalistic, user-friendly, and contemporary platform upon which to develop the next generation of everyday functioning assessments for HAND. Of note, the everyday functioning independence of individuals living with HIV infection is increasingly dependent on navigation of the World Wide Web to engage medical (e.g., pharmacy and health information), household (e.g., shopping and banking), and even psychosocial (e.g., social networking) resources. As such, the ecological validity and viability of the next generation of everyday functioning outcomes in neuroAIDS necessitates the development of Internet-specific performance- based tasks in order to enhance diagnosis and treatment of HAND. The aim of this R21 is to validate a series of novel, innovative tasks of everyday functioning (i.e., household shopping, financial management) that use a realistic, state-of-the-art web-based approach to evaluating HAND. The portability and health-relevance of these assessments are enhanced by a developmental aim that will engineer and pilot a naturalistic online health literacy search measure and a pharmacy refill and communication task on a mobile platform. We propose to recruit 100 persons with HIV infection (with a 50% prevalence of HAND) and 50 seronegative subjects from ongoing studies within the UCSD HIV Neurobehavioral Research Program (HNRP), thereby leveraging the comprehensive clinical characterization of these subjects at no cost to this grant. It is hypothesized that HIV infection will be associated with worse real world functioning on these web-based tasks, which will correlate with well-validated measures of health literacy (e.g., knowledge), neurocognition (e.g., executive dysfunction), and everyday functioning (e.g., medication management). It is expected that the web-based assessments will improve the diagnostic classification of HAND as compared to current standard- of-practice approaches. Accordingly, this R21 application proposes an important first step in determining whether Internet technology can be used to more accurately and effectively determine the real world impact of HIV infection. PUBLIC HEALTH RELEVANCE: People living with HIV infection commonly experience declines in cognitive functions (e.g., attention and memory) and related difficulties in managing their daily affairs (e.g., financial management) that represent a major burden to public health. HIV-infected individuals are increasingly using the Internet to manage their health (e.g., pharmacy), household (e.g., shopping and finances), and even psychosocial (e.g., social networking) affairs, but we presently have no clinical or research tools to detect the nature or extent of problems with this critical aspect of health and daily functioning. This study therefore takes an important first step in determining whether Internet technology can be used to more accurately and effectively determine the real world impact of HIV infection by developing web-based tests of health and household management.

DESCRIPTION (provided by applicant): Medication adherence rates among youth living with HIV are inadequate to effectively manage the disease, and novel interventions grounded in basic behavioral sciences are needed. Emerging evidence suggests that prospective memory (PM) could represent an important piece of the puzzle. PM is defined as the neurocognitive capacity to successfully form, maintain, and execute an intention at a particular point in the future in response to a specific cue. In response to PA-11-063, this proposal plans to translate basic cognitive neuroscience regarding PM into a more potent adherence intervention for YLH, a population at high risk for poor cognitive function, substance abuse, and poor adherence. While text message reminders are an increasingly popular adherence support, evidence of efficacy is equivocal particularly for the maintenance of adherence after reminders end. By using basic cognitive neuroscience to enhance the potency of technology- based interventions to improve PM for adherence tasks, we hope to achieve both greater initial gains as well as sustained improvements in adherence for youth with and without substance abuse. Although a larger trial is necessary to determine if substance abuse will moderate the effects of the intervention, the goal of this proposal is to develop a potent adherence intervention that can be used universally in this high-risk population. PA-11-063 specifies three phases of intervention development: 1) defining intervention target; 2) characterizing intervention effects; 3) assessing feasibility and refinement. In Phase 1, we will conduct theory-driven laboratory studies to improve three components of PM using a within-subjects design and traditional cognitive neuroscience tasks (strategic encoding, monitoring, and cue salience) in 60 youth from clinics where the co- PIs are based (San Diego and Detroit). In Phase 2, we will translate promising Phase 1 PM interventions to the youth's natural context to target adherence by combining them text messaging, and test for signals of efficacy using a multiple baseline design for YLH with suboptimal adherence (N=24; 12 with substance abuse and 12 without). In Phase 3, we will conduct a pilot randomized clinical trial comparing the technology-based PM adherence intervention to text message reminders (N=60).

Ensuring the successful development of the next generation of innovative research ideas and young scientists is critical to the continued advancement of high-impact translational science in neuroAIDS and addictions. Building on TMARC's success in supporting pilot studies and junior investigators during the past funding period, we propose to establish a formal Pilot and Developmental (PAD) Core for the renewal. The PAD Core will enable TMARC to expand the scope, rigor, and effectiveness of its already strong investment in serving as a resource-efficient incubator for innovative pilot studies and shaping individually-tailored developmental activities for trainees and junior investigators that will foster their professional growth in neuroAIDS and addictions research. Leadership of the PAD Core is multidisciplinary and brings considerable prior experience in training and the administration of developmental activities. The developmental program will assist trainees and junior investigators in matching with appropriate mentors and accessing TMARC scientific resources. The pilot grant program will involve annual calls for applications, which will Undergo formal scientific review by a nationally-recognized panel of external experts, the resource economy of which will be facilitated by linking the TMARC PAD Core to that of the HIV Neurobehavioral Research Center. After external review, the TMARC scientific leadership will evaluate highly rated proposals for their relevance to the Center's over-arching translational scientific aims and available resources before final funding recommendations are offered to NIDA program staff. In the current application, the PAD Core anticipates proposing 5 novel pilot studies for Year 1 that address issues germane to TMARC's METH/HIV aims, including real-world functioning (ludicello), cerebrovascular imaging (Croteau), social cognition (Sanders), cellular aging (Schrier), and vasculopathy (Soontornniyomkij). Each pilot: a) underwent a rigorous review process; b) is led by a junior investigator; c) has the potential to support external grant applications; and d) leverages the transdisciplinary resources of the Cores and Projects that support it. Abstracts of the Pilot Studies are found in the following pages.