Jason Mitchell - US grants

DESCRIPTION:(provided by applicant) The goal of the proposed research is to characterize the neural mechanisms underlying adaptive suppression of memory and memory-related judgments. Event-related fMRI will be used (a) to characterize the pattern of neural activity associated with encoding conditions that produce memory suppression, and (b) to identify which brain areas are predictive of successful memory suppression. Experiment 1 investigates the nature of illusory truth, in which perceivers have a difficult time suppressing their tendency to remember previously-presented statements as true. Experiment 2 directly tests some predictions, derived from my earlier work, about the role of selective rehearsal on the ability for subliminal cues to trigger standard directed forgetting effects. Finally, Experiment 3 attempts to bridge social psychology and cognitive neuroscience by examining how exposure to some social stimuli (e.g., pictures of elderly persons) can impact memory performance (an effect previously observed by Dijksterhuis, Aarts, Bargh, & van Knippenherg, 2000). We have adopted a functional imaging approach to these questions in order to examine specific predictions about the contributions of selective rehearsal and inhibition mechanisms in producing these suppression effects, tests of which are difficult or impossible to undertake in strictly behavioral research. We expect that against our current knowledge about the functional significance of many brain areas, these experiments will advance our understanding of the mechanisms giving rise to adaptive memory suppression, and not merely catalog the neural correlates of these effects.

[unreadable] DESCRIPTION (provided by applicant): Recently, cognitive neuroscience research has suggested the special status in the human brain of social cognitive processes such a representing the mental states of other people. Following from these earlier studies, the current research examines the functional neuroanatomy of social cognition along three distinct lines of inquiry. First, can neuroimaging data illuminate the mechanisms that give rise to well-known differences in memory and reasoning performance typical of social cognition (Expts 1 & 2)? Second, what constituent processes make up social cognition; that is, under what conditions are social cognitive processes engaged (Expt 3) are these processes sensitive to the type of social information being represented (Expt 4)? Finally, on the basis of extant neuroimaging work, novel predictions are tested regarding the status of social cognition as part of the default state of the human brain (Expts 5 & 6). Together, these experiments will improve current understanding of autism, a prevalent developmental disorder characterized by pervasive deficits in social cognitive processing, e.g., representing the mental states of other people. [unreadable] [unreadable]

Psychological scientists currently know little about how it is that one person infers the mental states of others even though successful social interaction requires that we be capable of inferring the content of another person's mind, an ability known as "mentalizing." This research involves the continued integration of theoretical questions from social psychology with the methods and tools of cognitive neuroscience. The first objective is to apply the methods of cognitive neuroscience to examine how perceivers mentalize about other people who differ from them along the "Big Three" dimensions of age, race, and sex. Researchers have suggested that two different routes to mentalizing may exist. First, perceivers may sometimes be able to "simulate" another person's mental states by imagining themselves in the same situation and assuming that others would share the same thoughts and feelings that they experience themselves. However, this simulationist strategy is only appropriate when the other person is sufficiently similar to self that he or she would indeed experience the same mental states as oneself. If the other person is dissimilar to the self (e.g., when someone has very different opinions or a very different cultural background0 perceivers frequently rely upon "precompiled" social knowledge in the form of stereotypes. Recently, researchers have used brain imaging techniques (e.g., fMRI) to suggest that a particular brain region : the medial prefrontal cortex (MPFC) : may show a tradeoff between mentalizing based on simulation and mentalizing based on stereotyping. The current project investigates the nature of this "division of labor" in the MPFC. In addition, this research examines the changes produced by several strategies for reducing stereotyping, as well as the dynamics associated with learning about the similarity (or dissimilarity) of another person to oneself. By illuminating the brain basis of social cognition, it represents a first step towards understanding the social dysfunctions evidenced by patients with disorders such as autism, conduct disorder, or sociopathy. The research also has the potential to contribute to societal attempts at reducing intergroup bias by suggesting new forms of education and public policy based on an enhanced understanding of the neural basis of stereotyping.

DESCRIPTION (provided by applicant): Current projections suggest that, by the year 2030, the population of older adults in the United States will be nearly twice what it was at the beginning of the 21st century, with one-fifth to one-quarter of Americans over 64 years of age. A sizeable amount of research in psychology has documented the cognitive difficulties that individuals may experience as they grow older, such as declines in episodic memory or other kinds of executive functions. However, recent data have also suggested that normal aging may be accompanied by declines not only in such cognitive functions, but also in the processes supporting social and emotional behavior. At the same time, clinical and social psychologicals have long observed that healthy socio-emotional functioning forms an important basis for well-being throughout one's life, correlating with both mental and physical health. Despite such suggestions that changes in socio-emotional processing may be an important aspect of aging, little is currently known about the underlying cognitive and neural basis of social cognition in this population or the precise nature of the social and emotional changes that may characterize normal aging. To this end, the main goal of the proposed research program is to investigate the cortical mechanisms and cognitive processes underlying social and emotional processing in healthy older adults. Guided by extant research, we propose examining two domains in which aging-related socio-emotional changes may be predicted: (1) the ability to infer the mental states of other people, i.e., mentalizing and (2) the ability to engage in cognitive regulation of one's affective experiences, i.e., emotional self-regulation. The proposed experiments have been designed to use a combination of behavioral and functional neuroimaging methods to study social and emotional processing in normal aging. The intended studies build on three distinct lines of extant research: (i) prior explorations of the functional neuroanatomy associated with making inferences about the mental states and behavior of other people (i.e., mentalizing);(ii) prior explorations of the functional neuroanatomy associated with voluntary regulation of negative emotional experience;and (iii) recent demonstrations that the brain systems important for both functions may be compromised in normal aging. Our goal is two-fold. First, we aim to examine potential aging-related changes in both social processing (such as inferring what another person is thinking or feeling) and control of one's emotions, as indexed by well- characterized behavioral tasks. Second, we aim to link such behavioral declines to changes in the underlying functional neuroanatomy previously associated with mentalizing and emotion-regulation tasks. Current projections suggest that by the year 2030, the population of adults over the age of 64 in the United States will be nearly twice what it was in 2002. Although a good deal of research in psychology has documented the cognitive difficulties that accompany healthy aging (e.g., declines in memory), more recent data have also suggested that older adults may experience changes in their social and emotional functioning (e.g., becoming less socially motivated and more socially isolated). Using a combination of cognitive experiments and brain imaging (fMRI), the proposed experiments will examine the functional basis of social and emotional behavior in older adults, with an eye towards better understanding the nature of aging-related changes in these central human faculties.

Functional magnetic resonance imaging (fMRI) has become the most common tool for cognitive neuroscience, because it provides a safe, non-invasive, and powerful means to image human brain function. Based on recent rates of publication, there are currently more than 2000 fMRI studies being performed every year worldwide. The aggregation of data across multiple studies can provide the ability to answer questions that cannot be answered based on a single study. For example, using datasets from multiple domains one can start to investigate to what degree a region is selectively engaged in relation to a particular mental process, as opposed to being generally engaged across a broad range of tasks and processes. In addition, it provides the ability to integrate across specific tasks to obtain stronger empirical generalizations about mind-brain relationships, and to better understand the nature of individual variability across different measures. Recent work in neuroimaging analysis has focused on the application of methods such as machine learning techniques to understand the coding of information at the macroscopic level, and network analysis techniques to understand the interactions inherent in large-scale neural systems. The availability of a large testbed of high-quality fMRI data from published studies would also provide an important resource for the development of these and other new analytic techniques for fMRI data. However, sharing of raw fMRI data is challenging due to the large size of the datasets and the complexity of the associated metadata, and there is currently no infrastructure for the open sharing of new fMRI datasets.

This project, OpenfMRI, will provide a new infrastructure for the broad dissemination of raw data within cognitive neuroscience, addressing a critical need by providing an open data sharing resource for neuroimaging. The initial project is already online at http://www.openfmri.org with a limited number of datasets. The full project will greatly expand this repository by providing access to a large number of fMRI datasets from several prominent neuroimaging labs, spanning across a broad range of cognitive domains. Utilizing the substantial computational resources of the Texas Advanced Computing Center, the project will also perform standard fMRI analyses on all data in the repository using a common analysis pipeline, thus providing directly comparable analysis results for all of the studies in the database. The OpenfMRI project will support the development of infrastructural elements to make sharing of data by additional investigators more straightforward.

The repository of data that will be created by the OpenfMRI project will also serve as an important resource for teaching by providing students with the ability to replicate the analyses from published studies using the same data. By providing any researcher in the world with the ability to acquire large fMRI datasets, it will also provide all researchers with the ability to work with the same state-of-the-art datasets, regardless of institution. By creating the infrastructure for open sharing of research data, the project will also enhance the impact of other NSF-funded neuroimaging research projects by providing an infrastructure that can be used to make their data available. The planned work has the potential to benefit society by improving education, health, and human productivity through an increased understanding of mental function and its relationship to brain function.

DESCRIPTION (provided by applicant): Social isolation has considerable effects on human functioning. However, despite the well-established effects of social isolation on physical and mental health, remarkably little is known about the proximal cognitive and neural changes that produce such deleterious outcomes. Studies that have manipulated social isolation report contradictory findings-social isolation can at times increase engagement toward social cues but also diminish engagement with others. The present research aims to reconcile these contradictory findings by testing the hypothesis that social isolation has opposing effects on two different brain systems!one of which leads to hypersensitivity to social stimuli and one of which leads to a reduction in the value associated with social engagement. In doing so, this program of research also makes us of a newly-developed strategy for manipulating social isolation. To date, most researchers have manipulated disconnection as exclusion or ostracism. However, such operationalizations only capture forms of social disconnection that involve rejection, but do not examine an extremely prevalent naturally- occurring form of social isolation: sheer lack of contact with others!social deprivation. To address this shortcoming of earlier research, we will manipulate social isolation as acute social deprivation, in which individuals are actively restricted from contact with others for a relatively long period of time. This operationalization presents an innovation in simulating the common experience of merely being alone rather than being actively rejected by others. The proposed research will use magnetic resonance imaging (MRl) to test the effect of social deprivation on several aspects of social cognition, including th tendency to perceive social cues such as mental states and emotional expressions and the valuation of social rewards. As such, this research aims to shed light on a pervasive cause of isolation that researchers have typically studied only with nonhuman animals (e.g., rats) or in already socially deprived individuals (e.g., prisoners). We propose two experiments that test three specific aims. The first experiment tests the extent to which social deprivation increases social cue detection and mind perception, consequently increasing activation in brain regions associated with social cognition. The second experiment tests the extent to which social deprivation decreases the value associated with social rewards, consequently decreasing activation in brain regions involved in reward processing. In addition, arterial spin labeling and functional connectivity analyses will be administered on brain scans taking during periods of rest during these studies. These methods allow us to test the hypothesis that social deprivation will lead to increased basal metabolic activity and increases the coordinated activity in the brain's default network, a network involved in social cognition.

DESCRIPTION (provided by applicant): Current estimates indicate that between 58% and 78% of MSM in the US acquire HIV from their main partners within the context of a same-sex relationship (e.g., male couples). Studies with male couples have examined which factors, including sexual agreements, impact their risk for acquiring HIV. Many male couples in the US form a sexual agreement: an explicit agreement made between two partners about what sexual and other behaviors may occur within and outside of their relationship. By nature, couples' sexual agreements have direct implications toward their risk for HIV and other STIs. Because few HIV prevention interventions exist for male couples, new and novel approaches that consider the relational context of male couples are urgently needed to significantly improve HIV prevention. To help fulfill this critical gap, the proposed 3-year study aims to develop and pilot theoretically derived, web-based HIV prevention toolkit for at-risk HIV-negative male couples in the US. Through the completion of modules, the interactive HIV prevention toolkit will guide and assist at-risk HIV-negative male couples who currently practice unprotected anal intercourse (UAI) - the primary sexual risk behavior for HIV acquisition among MSM - form an explicit sexual agreement that integrates interval testing for HIV and STIs and prevention messaging while uniquely meeting the needs of their relationship. The web-based prevention toolkit will consist of two components: an interactive website that contains theoretically-based modules for couples to complete while forming their agreement, and a corresponding smartphone application (app) that will contain a copy of the agreement along with a list of GPS- enabled sexual health resources, such as where they can test for HIV and STIs, and access free safer sex supplies and biomedical approaches to prevention. Development of the prevention toolkit will occur through 3 phases. In Phase 1, we will conduct individual- and couple-level interviews in Detroit and Atlanta with 30 HIV- negative male couples who practice UAI and currently have a sexual agreement (15 open, 15 closed) to obtain feedback about the content in the prevention toolkit modules, derived from our extensive previous HIV prevention studies about male couples' sexual agreements and relationship dynamics. Feedback obtained from Phase 1 will be integrated to improve the content of the modules, and used by the software company to design the first version of prevention toolkit. Phase 2 will include conducting 2 focus groups, one in Detroit and one in Atlanta, with 7 HIV-negative male couples to pilot test the content of the modules, and obtain feedback about the appeal and ascetics of the interactive exercises and components of the prevention toolkit. By integrating findings from Phase 2, further refinements will be made to the prevention toolkit before beginning to pilot test the intervention. For Phase 3, a small prospective RCT with a 6-month follow-up period will be conducted via the Internet with a national convenience sample of 160 at-risk HIV-negative male couples to determine whether couples who receive the intervention (i.e., prevention toolkit) will form and adhere to their sexua agreement, increase their testing rates for HIV and STIs, and abstain from or decrease their occurrences of UAI with casual MSM partners when compared to couples in the control group. The proposed study is innovative because technology is appropriately used to maximize reach and impact while uniquely tailoring to the needs of each couple. We anticipate our pilot intervention will show promise for reducing male couples' HIV risk, which would then be further tested for efficacy through a larger RCT.

DESCRIPTION (provided by applicant): Despite current testing promotion efforts to critically reduce the rate of new HIV infections in the US, men who have sex with men (MSM) may not be aware of the need or motivated to test for HIV/STIs at regular intervals. Current HIV testing guidelines recommend at least annual testing, with more regular testing (every 3 to 6 months) for those with identifiable risk factors, including substance use and having multiple or anonymous sex partners. However, recent studies show that one-third of US MSM have not tested for HIV in the past year, despite the trend of increasing unprotected sex between 2005 and 2011 in this population. To address this gap, we propose a 3-year study to develop and pilot test a tailored, theoretically-based (in the Information- Motivation-Behavioral Skills model) smartphone application (or app) intervention to facilitate regular HIV testing among a diverse nation-wide sample of MSM who are at-risk for HIV. Derived from our extensive HIV prevention research with MSM, core components of the smartphone app intervention will include: a) regular assessment of risk behaviors via personal profile; b) tailored recommendations for frequency of HIV testing based on individual's risk patterns and profile; c) GPS-enabled HIV testing location finder; d) motivational messages addressing critical barriers to testing; and e) a graphically appealing interface tailored to the unique cultural and social preferences of MSM. The study will be conducted in 3 phases with corresponding aims. In Aim 1, 6 focus groups of high-risk MSM will be conducted in 2 US cities (Minneapolis, MN and Detroit, MI) to determine which app features and functions are most likely to support downloading, initiating use, and sustaining engagement over time of the tailored HIV/STI testing app. The smartphone app will be developed in collaboration with our technology partner in Aim 2, and usability tested among 6 members of the target population in Detroit, MI and Minneapolis, MN. Finally, the goal of Aim 3 is to assess the feasibility and acceptability of the smartphone app intervention to promote regular HIV testing at tailored, prescribed intervals among racially and ethnically diverse US MSM. A national sample of 120 at-risk HIV-negative/unknown MSM who have not been tested for HIV in the past year will be randomly assigned to either the experimental (n=60) or control condition (n=60) and followed for 6 months, with assessments at baseline, 3- and 6-months. The control condition will be a non-tailored, information-only version of the HIV testing app. In addition to feasibility and acceptability measures, preliminary effect estimates will be calculated to inform a subsequent R01 trial. This proposed study would help advance science of HIV prevention interventions by harnessing smartphone app technology to promote regular testing among US MSM who at-risk for acquisition of HIV. Findings will inform the development and implementation of a large, national RCT study to test for efficacy. If effective in the subsequent R01 trial, the intervention will be readily available for scale-up for national dissemination by partnering with clinics, community-based organizations, and websites used by MSM in the US.

ABSTRACT ?Hierarchical influences on PrEP use, willingness and readiness among male couples? The incidence of HIV continues to increase among men who have sex with men (MSM) continues to increase. Moreover, between one- and two-thirds of MSM in the US acquire HIV from their main partners while in a relationship (i.e., male couples). Although a growing interest in male couples' relationships has emerged in HIV prevention research, few studies have been conducted about their attitudes, support, current use and unsuccessful attempts of obtaining of pre-exposure prophylaxis (PrEP). PrEP ? a daily regimen of ART (i.e., Truvada?) taken by those who are HIV-negative to prevent the acquisition of HIV ? is a promising biomedical approach to preventing new HIV infections among MSM and male couples alike. To date, most research studies have investigated how individual-level factors are associated with MSM's attitudes to use PrEP. Currently, two of CDC's three guidelines for administering PrEP pertain to those who are in a relationship yet very few studies have explored men's perceptions of how casual and main partners affect their PrEP uptake and even fewer studies have collected data from both men of the couple. Beyond the dyadic level of being in a relationship, there is the potential for community and social network factors to shape PrEP attitudes, support, and uptake, but these influences are also largely currently under-explored. To respond to this critical gap in understanding how relational/dyadic, community and social network factors affect PrEP uptake among male couples, we propose to conduct a novel two-year mixed method project to collect in-person, quantitative dyadic data from 100 self-reported HIV-negative and 100 self-reported HIV-discordant male couples in Miami, FL and Detroit, MI. From this sample of 200 dyads, a subsample of participants and their main partner (~N=40 dyads/n=80 men) will be interviewed, individually and simultaneously, about their unsuccessful attempts to obtain PrEP and the factors associated with these unsuccessful attempts. Our purposive English or Spanish speaking sample will be drawn from targeted electronic advertisements on a range of social media used by MSM. The advertisements will reflect the diversity of the MSM populations in these two cities and who are most severely impacted by HIV (e.g., Black and Hispanic MSM, younger MSM). To address how different levels of factors may impact PrEP uptake among male couples, our study will be guided by Bronfenbrenner's Ecological Model paired with advanced analytic methods. Our project's overall aim is to examine how individual, dyadic, social network and community factors shape support, willingness, current use, and unsuccessful attempts to adopt PrEP among a diverse sample of 100 concordantly HIV-negative and 100 HIV-discordant male couples from two U.S. cities that lack substantial PrEP resources. The proposed findings will highlight which hierarchal factors and actor-partner effects reinforce PrEP support, willingness, current use, and unsuccessful attempts among at-risk male couples. Findings from this novel, efficient study will help inform the development of effective PrEP messaging for male couples and will also shape the development of future dyadic interventions.

? DESCRIPTION (provided by applicant): Despite between one- and two-thirds of US men who have sex with men (MSM) acquire HIV from their primary 4 same-sex relationship partner (i.e., male couples), most HIV prevention efforts have targeted MSM at the 5 individual- and community-levels. Substance use is also an important Public Health issue that affects HIV 6 acquisition and transmission among MSM; substances are often used to enhance pleasure and sustain 7 engagement in sexual behaviors including condomless anal sex (CAS). Findings from the few studies 8 conducted with male couples indicate their use of substances with sex negatively impacts their relationship 9 dynamics and behaviors related to HIV prevention, including CAS with casual MSM partners and poor 10 treatment adherence. Although these findings suggest the need to intervene for prevention, less is known 11 about how primary partners within the male couple influence one another's use of substances, the different 12 context(s) in which they use substances, and how their usage directly affects their risk for HIV and dynamics of 13 the relationship. To that calling, we propose to conduct a 4-year mixed method study that is theoretically 14 grounded to examine how male couples' use of substances affects their relationship and risk for acquisition 15 and/or transmission of HIV. We will use venue-time sampling to recruit 225 substance-using male couples, 16 diverse in terms of HIV status and relationship length, from community and Internet venues in South Florida. 17 We will collect qualitative and quantitative longitudinal dyadic data over a 6-month period to examine the 18 associations between intrapersonal, interpersonal and contextual factors in general and with event level 19 substance use. Participants will complete in-person ACASI at 3 time points (baseline, 3 and 6 months), and 20 daily ecological momentary assessments (EMA) during months 2 and 5. Every third reported substance use 21 event will be supplemented with an in-depth phone interview. All data will be collected independently from each 22 partner of the couple, and couples' substance use and HIV serostatus will be verified at baseline, 3 and 6 23 months. Longitudinal quantitative data obtained from the ACASI and EMA will be analyzed using 24 mixed/multilevel models, including actor-partner effects. Qualitative content analysis, specifically latent and 25 manifest content analysis, will be used to identify and describe the major themes and sub-themes that emerge 26 from the phone interview data. We will use standard mixed methodology to integrate the quantitative and 27 qualitative findings to elucidate how primary partners' influence one another's use of substances and risk for 28 HIV, and how their usage affects dynamics of their relationship. Under the direction of Mitchell, he and his 29 team of senior co-investigators will disseminate these findings, and apply them toward development of a 30 couples-focused HIV and substance use preventive intervention for use in a future project.

SUMMARY / ABSTRACT Gay, bisexual, and other men who have sex with men (MSM) continue to be the group most heavily impacted by HIV in the United States, despite stability or decline in infections among other groups. Up to two-thirds of MSM acquire HIV from their main partner (i.e., male couples). Given the multitude of available HIV prevention options, HIV-negative and HIV-discordant male couples may experience anxiety and decisional conflict in determining which HIV prevention methods to use in their relationship. Moreover, uptake of different evidence- based preventive strategies (e.g., PrEP, nPEP, couples- and individual-level HIV/STI testing) remains subpar in these two groups of male couples, which inhibits the overarching goal to reduce HIV and STI incidence. Patient-centered decision aids (PtDAs) have been shown to reduce decisional conflict and increase uptake of preventative behaviors; however, there are no existing couples-based HIV prevention PtDAs to assist male couples in choosing and then using their selected strategy(ies). The overarching goal of this two-year, mixed method project is to develop and examine the to develop and examine the feasibility, acceptability, and preliminary efficacy of a tailored, web-based interactive PtDA to encourage a convenience sample of 45 at-risk male couples in new relationships to develop a prevention plan, and order and use their selected prevention strategies based on their plan. Method: All project activities will be web-based. First, semi-structured, individual qualitative interviews will be conducted with both partners of 45 male couples (n=90 men), who are in new relationships, to examine perceived barriers and facilitators of partners? decision-making processes to use prevention strategies in their relationship (Aim 1). Findings from Aim 1 will be combined and applied to the proposed outline, design, and experience of the PtDA with the web development company, consultant, and community advisory board (CAB). The CAB and investigative team will then test the prototype and alpha version of the PtDA before beginning Aim 2 with the beta version of it. With the use of a different convenience sample of 45 eligible male couples in new relationships (Aim 2), the feasibility, acceptability, and preliminary efficacy of the PtDA will be assessed to determine whether couples developed a prevention plan for uptake and/or continued use of their selected HIV preventive strategy(ies). Dyadic data will be captured via: 1) brief, quantitative, pre- and post-intervention assessments taken at baseline and 2 months; 2) selections made within the PtDA; 3) pictures provided by participants about use of strategies; 4) semi-structured individual, exit interviews conducted at 2 months. The sample ? for both aims ? will be stratified (e.g., race/ethnicity, couples? HIV-status). Significance: If acceptability of the HIV prevention PtDA is high and shows initial promise to improve uptake and use of evidence-based strategies, our findings will support follow-up with a R01 application to test the intervention efficacy in a fully powered randomized controlled trial with a larger diverse sample of at- risk male couples in new relationships throughout the U.S.

Couples HIV testing and counseling (CHTC, known as Testing Together) entails both partners of the couple receive counseling, test for HIV/STIs, and obtain their test results together. The majority of studies involving heterosexual couple-based HIV risk reduction interventions in the US, including CHTC, have been conducted with specific subgroups (e.g., drug-users) and/or occurred in a specific location (e.g., methadone clinics). Although these projects have demonstrated effectiveness for reducing HIV risk, implementation and uptake of CHTC to capture a wider range of mixed-sex couples is critical as heterosexual sexual transmission accounts for 25% of new HIV infections in the US. As such, additional research is needed to identify barriers and facilitators of CHTC uptake among mixed-sex couples. Offering CHTC to a larger number and wider range of couples would help increase identification of serodiscordant dyads, link newly diagnosed partners to HIV care and treatment, and promote the uptake of other primary prevention strategies (e.g., condoms, PrEP) among those who receive a HIV-negative test result. CHTC also enables couples to create a risk-reduction strategy based on their joint HIV test results, and sexual health and relational preferences. However, implementation and training needs of HIV test counselors must also be considered to increase uptake of CHTC among more mixed-sex couples in the US. Thereby, we propose to conduct a novel, mixed method, two-year project with a nation-wide sample of 300 mixed-sex couples, and 25 HIV test counselors who provide CHTC, as well as 25 HIV test counselors who are CHTC untrained/naïve. All study activities will occur online through established protocols by using HIPAA-compliant web servers, survey software, and video portals. Led by an established PI, expertise of the team includes qualitative, quantitative, and mixed methods, dyadic data analysis, online research, CHTC, and HIV risk-related behaviors, complemented with the necessary experience of working with couples and HIV test providers. To begin, we will conduct a nation-wide, cross sectional survey to collect quantitative dyadic data from 300 mixed-sex couples to assess their willingness to use CHTC and associated factors (Aim 1). We hypothesize that couples will fall into 3 groups on whether both, neither, or only one partner (i.e., discrepant) is willing to use CHTC. Among these 300 couples, we will then randomly select 30 couples to conduct qualitative interviews with equal representation from each of these 3 groups to explore and contextualize their perceived barriers and facilitators toward using CHTC; both partners will be interviewed separately and simultaneously (Aim 2). Finally, we will conduct qualitative interviews with 50 HIV test counselors (25 provide CHTC, 25 untrained) to examine and identify their implementation and training needs to provide CHTC to more mixed-sex couples (Aim 3). Our findings will help identify what additional implementation and training needs are required for HIV test counselors, as well as the strategies to increase willingness to use CHTC to achieve greater uptake of CHTC among more mixed-sex couples in the US.

? DESCRIPTION (provided by applicant): Despite between one- and two-thirds of US men who have sex with men (MSM) acquire HIV from their primary 4 same-sex relationship partner (i.e., male couples), most HIV prevention efforts have targeted MSM at the 5 individual- and community-levels. Substance use is also an important Public Health issue that affects HIV 6 acquisition and transmission among MSM; substances are often used to enhance pleasure and sustain 7 engagement in sexual behaviors including condomless anal sex (CAS). Findings from the few studies 8 conducted with male couples indicate their use of substances with sex negatively impacts their relationship 9 dynamics and behaviors related to HIV prevention, including CAS with casual MSM partners and poor 10 treatment adherence. Although these findings suggest the need to intervene for prevention, less is known 11 about how primary partners within the male couple influence one another's use of substances, the different 12 context(s) in which they use substances, and how their usage directly affects their risk for HIV and dynamics of 13 the relationship. To that calling, we propose to conduct a 4-year mixed method study that is theoretically 14 grounded to examine how male couples' use of substances affects their relationship and risk for acquisition 15 and/or transmission of HIV. We will use venue-time sampling to recruit 225 substance-using male couples, 16 diverse in terms of HIV status and relationship length, from community and Internet venues in South Florida. 17 We will collect qualitative and quantitative longitudinal dyadic data over a 6-month period to examine the 18 associations between intrapersonal, interpersonal and contextual factors in general and with event level 19 substance use. Participants will complete in-person ACASI at 3 time points (baseline, 3 and 6 months), and 20 daily ecological momentary assessments (EMA) during months 2 and 5. Every third reported substance use 21 event will be supplemented with an in-depth phone interview. All data will be collected independently from each 22 partner of the couple, and couples' substance use and HIV serostatus will be verified at baseline, 3 and 6 23 months. Longitudinal quantitative data obtained from the ACASI and EMA will be analyzed using 24 mixed/multilevel models, including actor-partner effects. Qualitative content analysis, specifically latent and 25 manifest content analysis, will be used to identify and describe the major themes and sub-themes that emerge 26 from the phone interview data. We will use standard mixed methodology to integrate the quantitative and 27 qualitative findings to elucidate how primary partners' influence one another's use of substances and risk for 28 HIV, and how their usage affects dynamics of their relationship. Under the direction of Mitchell, he and his 29 team of senior co-investigators will disseminate these findings, and apply them toward development of a 30 couples-focused HIV and substance use preventive intervention for use in a future project.

1 SUMMARY / ABSTRACT 2 3 Sexual minority men in Lima, Peru are disproportionately impacted by HIV, and a substantial proportion of these 4 men acquire HIV while in a relationship (i.e., cisgender male couples). Studies conducted by members of the 5 investigative team found that cisgender male couples? use of evidence-based HIV/STI prevention strategies (e.g., 6 ART, PrEP, routine HIV/STI testing, condom use) are sub-optimal to reliably prevent acquisition and/or 7 transmission of HIV and other STIs given their current engagement in sexual risk behaviors. To date, no couples- 8 based HIV/STI prevention interventions are available in Lima or elsewhere in Peru. The overarching goal of the 9 proposed 3-year project is to help fill this critical gap in Peru?s HIV/STI prevention services. To start, we 10 conducted a mixed method pilot project to assess the acceptability of the PI?s theoretically-grounded eHealth, 11 couples-based HIV/STI prevention toolkit intervention with 42 cisgender male couples in Lima (14 concordant 12 HIV-negative, 16 discordant, 12 concordant HIV-positive). 90% of couples reported high acceptability of the 13 intervention, and liked the agreement builder activity the most. Couples told us they wanted more information 14 about HIV treatment as prevention (PrEP, ART, TasP/U=U) and how to strengthen and manage their own and 15 familial relationships (cultural context). They also wanted the intervention to be accessible on different web- 16 connected devices. Additional findings revealed only 33%-50% of couples included evidence-based HIV/STI 17 prevention strategies in their agreement. To help improve couples? uptake and continued use of evidence-based 18 prevention strategies, our solution is to integrate an electronic algorithm into the agreement builder activity to 19 provide them with tailored recommendations that align with their engagement in sexual behaviors and 20 relationship profile. Methods: Via the proposed R34, our next steps are to apply the remaining stages of the 21 ADAPT-ITT model with elements of human-centered design to adapt our couples-based intervention. We will 22 then conduct a 6-month pilot RCT with a waitlist control to assess the feasibility, acceptability, and preliminary 23 impact of the adapted intervention with 60 cisgender male couples, stratified by their dyad HIV serostatus, on 24 outcomes of: a) formation and adherence to a tailored risk-reduction plan and agreement; b) relationship 25 functioning (e.g., communication); c) use of evidence-based HIV prevention strategies; and d) HIV/STI incidence 26 over time. Our proposed approach is rigorous with scientific premise as mixed methods and a pilot RCT with 27 a waitlist control will be used to achieve our Specific Aims. Our project is also timely and practical with key 28 stakeholder buy-in, suggesting the high Public Health significance of our proposal. Our findings will reveal the 29 feasibility, acceptability and preliminary impact of the adapted toolkit intervention to reduce couples? HIV/STI risk 30 via sustained use of evidence-based HIV prevention strategies over time through their formation and adherence 31 to a tailored agreement and risk-reduction plan. Our next step will be to apply these findings (e.g., R01) to test 32 the intervention for efficacy. Our project is of interest to NOT-MH-20-019 and NOT-MH-20-020.

1 SUMMARY / ABSTRACT 2 3 Between one to two-thirds of new HIV infections among MSM are attributable to sex with main partners (i.e., 4 male couples).1,2 48% of HIV-positive MSM in 5 US cities who were HIV tested in CDC's NHBS project were 5 unaware of their status,3 suggesting the potential for high levels of unknown sero-discordance among male 6 couples. Research has also illustrated the role that relationship dynamics (e.g., HIV-specific social support, 7 constructive communication, sexual agreements) have in shaping male couples' risk for HIV4-41; this has also 8 been shown longitudinally, strongly suggesting that promoting positive relationship dynamics is a significant 9 intervention point for reducing HIV transmission among male couples.42-44 There is also evidence at-risk male 10 couples can work together towards shared HIV prevention and care-related goals, including PrEP and U=U/TasP 11 that rely on adherence and resultant viral suppression, leading to increased health and reduced likelihood of 12 onward HIV transmission.45-55 Innovative and tailored solutions are needed to meet the HIV prevention and care 13 needs of at-risk male couples. Our solution is to leverage our strong findings from the preliminary work we 14 conducted in the US (R34 pilot RCT & mixed method acceptability project)59-62 to propose a highly novel, 5-year 15 project to revise and update an existing, eHealth couples-based HIV/STI prevention toolkit intervention that 16 showed promise for reducing couples' HIV risk. The intervention is theoretically grounded in Couples 17 Interdependence Theory for health behavior change.63,64 We will first apply the remaining stages of the ADAPT- 18 ITT model65 with elements of human-centered design66-69 to incorporate at-risk, sero-concordant negative and 19 sero-discordant male couples' prevention and relationship needs while also including the latest science in 20 HIV/STI prevention. We will then conduct a 16-month RCT with 300 at-risk male couples using a delayed, 21 educational control condition of 8 months. Our Specific Aims are to: 1) examine efficacy of the intervention on 22 couples' a) formation and adherence to a risk-reduction plan and agreement, b) relationship functioning, c) self- 23 reported and biomarker confirmed indicators of risk (sexual behavior and STI), and engagement in HIV 24 prevention (PrEP adherence) and care (ART adherence); 2) evaluate use of the intervention over time by using 25 three different data sources; 3) explore moderating and mediating effects on couples' outcomes a-c. Our proposal 26 has high Public Health significance given the HIV disparities and importance of attending to couples' unique 27 relationship and prevention needs. Our innovative, accessible, and tailored intervention will fill a gap in current 28 prevention services by offering couples a personalized program. We believe results from the fully powered RCT 29 will show efficacy toward improving sustained HIV prevention outcomes among at-risk male couples in the US. 30 The scientific premise and rigor will further allow us to understand the processes that couples work together 31 to manage HIV/STIs in their relationships. Our next steps may include conducting a Type 1 Hybrid Trial to assess 32 for effectiveness and explore best practices for future implementation.70