Keith J. Horvath, Ph.D. - US grants

DESCRIPTION (provided by applicant): The HIV epidemic continues to be a significant public health threat in the United States (US), particularly as HIV-positive (HIV+) individuals live longer as a result of improved treatments. However, poor adherence to highly active antiretroviral therapy (HAART) is common, and has a high societal cost in terms of medical expenditures associated with suboptimal adherence. The long-term objective of this proposal by a new investigator is to increase medication adherence among HIV+ individuals in the US. To achieve this, the specific aims are to: 1) conduct formative research on medication adherence and its risk factors among Internet-using HIV+ persons, 2) design a peer support Internet-based HIV medication adherence intervention grounded in the Information-Motivation-Behavioral Skills theory;and 3) pilot the online intervention to assess intervention feasibility and procedures, as well as to obtain population parameters to calculate more precise power and design estimates for a future randomized controlled trial. We propose to develop core intervention components that include user-driven personal profiles that enable participants to communicate with one another and receive peer support, medication self-monitoring and e-mail and text message reminders, and tailored IMB-related feedback that address common problems of adherence. All intervention features will be highly mobile to allow for utilization in contexts in which adherence problems arise. Innovation in this project includes the use of a theoretically-grounded and empirically-derived Internet- based intervention to address HAART adherence, with incorporation of peer interaction and self-monitoring features that have not been widely used in HIV-related online interventions. The PI is experienced in Internet-based HIV-related intervention research, and has assembled a strong multidisciplinary team - representing Epidemiology and Community Health, Psychology, Computer Science, and Pharmacy - to develop the first of its kind intervention. The HIPS Program environment has a national reputation in online HIV prevention studies, and has developed extensive protocols for human subjects'considerations, including data security and cross-validation protocols, which are identified barriers to effective Internet- based research. The significance to HIV treatment adherence research of this proposal includes the development of a comprehensive approach to theoretically-grounded online intervention development and implementation, empirically-based in formative research to understand the risks and needs of Internet-using HIV+ individuals and the use of technology standards for future adherence efforts. The significance of this project to public health involves the development and pilot testing of the first online HAART medication adherence intervention for Internet-using HIV+ individuals that, if successful, can be easily adapted for a more definitive subsequent randomized controlled trial. PUBLIC HEALTH RELEVANCE: The proposed project is to a) conduct formative research on medication adherence and its risk factors among Internet-using HIV-positive individuals and b) design and pilot a theoretically grounded, peer support online HIV medication adherence intervention. The impact of the proposed intervention at the individual level is the reduction of HIV viral load, thereby curtailing progression to AIDS, and at the societal level, by reducing health care costs that result from poor adherence. Using the Internet to deliver the intervention will allow it to be distributed widely and adapted for use with a variety of populations.

DESCRIPTION (provided by applicant): Stimulant use is prevalent among men who have sex with men (MSM) and is associated with sub-optimal adherence to antiretroviral therapy (ART), poor clinical outcomes, and sexual risk-taking. Moreover, MSM represent a unique population, whose intervention needs vary from their heterosexual counterparts. For these reasons, HIV-positive stimulant-using MSM (HIV+ SU-MSM) require ART adherence interventions tailored to their unique context, concerns, and lifestyle. Despite this urgent need, no technology-based ART adherence interventions specifically tailored to the needs of HIV+ SU-MSM have been developed and assessed for feasibility and acceptability with this population. We will use a three-phase approach to develop and assess the feasibility and acceptability of a smart phone application (app) ART adherence intervention tailored to the needs of HIV+ SU-MSM and grounded in the Information-Motivation-Behavioral Skills (IMB) model. Aim 1 will consist of 4 online focus groups (8-10 men each) to identify smart phone app contents and functions to maximize interest among HIV+ SU-MSM in downloading an ART adherence app, initiating its use, and maintaining engagement with the app over time. In addition, focus group participants will be asked to describe their ART adherence informational, motivational and behavioral skills needs. Lessons from the focus groups will be used in Aim 2 to develop a novel smart phone app tailored to HIV+ SU-MSM to improve their ART adherence. Intervention components will consist of tailored informational messages, a motivational personal intervention guide, medication reminders, ART and drug use self-monitoring, self-reflection and strategy rehearsal. The intervention will be usability tested among five participants prior to finalizing the look and content. The developed intervention will be pilot tested among 76 HIV+ SU-MSM in Aim 3. HIV+ SU-MSM randomized to the intervention group (n=38) will participate in the smart phone app intervention for 60 days, while control group (n=38) participants will receive treatment-as-usual through their existing medical care. Group adherence outcomes will be compared at baseline, post-intervention, and 3- and 6-month follow-up. Among participants randomized to the intervention group, daily patterns during the intervention period will be examined to assess app component use, percent of ART doses taken, rating of suggested strategies to overcome adherence barriers, experiences of drug cravings and use of stimulants. These and other feasibility (e.g. days per week accessing the intervention, overall retention) and acceptability (e.g., self-reported acceptability and user engagement) measures will be collected throughout the study period to inform a subsequent large scale RCT trial. The primary significance of the proposed research to public health is to improve ART adherence among substance-using populations and reduce rates of HIV transmission among MSM. If found effective, the smart phone app intervention will be readily available for scale-up for national dissemination through partnering with HIV clinics in high-burden regions, and in low-resource and rural areas.

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.

? DESCRIPTION (provided by applicant): Studies show substantial benefit to reduce morbidity and excess mortality for people living with HIV (PLWH) who adhere to antiretroviral therapy (ART), and to lower the probability of forward transmission to sexual partners. Despite efforts to maintain engagement of PLWH along the treatment cascade, it is estimated that only 19-25%% of PLWH and 27% of MSM in the US maintain suppressed viral load (VL). Several technology- based ART adherence interventions have demonstrated efficacy, however all have been individually delivered and have failed to leverage Web 2.0 features. While peer-to-peer social support is a recommended strategy to improve ART adherence and has enormous immediate appeal as a generalizable intervention approach, no peer-to-peer social support ART adherence interventions have been tested in a full-scale efficacy trial. The Thrive with Me (TWM) intervention is a technology-delivered peer-to-peer social support intervention grounded in the Information, Motivation, and Behavioral Skills (IMB) model for HIV-positive MSM. In addition to asynchronous peer-to-peer support capabilities, the TWM intervention provides participants with ART adherence self-monitoring tools, medication dose reminders, and HIV-related informational content. A pilot study of the TWM intervention demonstrated feasibility and acceptability of this approach; results showed that the TWM intervention group self-reported improvement in adherence at follow-up compared to the usual care control group, with greatest gains evident among recent drug users. Based on the encouraging findings of TWM study and the need for novel, evidence-based effective ART adherence interventions, we propose the following study aims. Primary aims (Aims 1 and 2) are to examine the efficacy of the online and mobile- enabled TWM intervention in a full-scale randomized controlled trial. HIV-positive MSM with detectable VL residing in New York City will be randomized to receive the TWM intervention or an information-only HIV/ART intervention for a 5-month period. Recruitment will be stratified by recent drug use, such that half will report recent illicit drug use. VL, validated self-reported AR adherence, and intervention utilization measures will be collected at baseline, post-intervention, and 5-, and 10-month follow up. We hypothesize that participants in the TWM intervention will demonstrate significant improvements in self-reported ART adherence and VL at each follow-up time point compared to control participants, with greatest improvements among recent drug users. Aim 3 (a secondary aim) is to examine the effects of the intervention on theory-based change processes (i.e., IMB factors and social support) for improving VL, ART adherence, and substance use outcomes. The proposal is innovative for its use of mobile and online technology as an ART adherence intervention delivery tool, and for being the first technology-delivered peer-to-peer support ART adherence intervention. The public health significance of the proposed study is that it advances ART adherence intervention for persons in greatest need of intervention and, if effective, may be quickly scaled up for dissemination.

Abstract Young men who have sex with men (YMSM), especially those who are Black and Hispanic/Latino, are disproportionately impacted by new HIV infections. Pre-exposure prophylaxis (PrEP) is one of the most effective HIV prevention tools, however its benefits are directly correlated with medication adherence to sustain adequate tenofovir (TFV) levels in blood. Recent studies (ATN 110 & 113) show that young MSM prescribed PrEP struggle with adherence, especially when healthcare appointments are reduced from monthly to every 3 months, and most fail to maintain protective drug levels via PrEP over time. This has prompted calls for youth- specific interventions consisting of peer support groups and frequent healthcare interactions for YMSM on PrEP. The proposed study responds directly these recommendations by developing and pilot testing a mobile peer support intervention to improve PrEP adherence and retention in PrEP care for YMSM ages 18-29 years, called ?PrEP it Together? (or PrEP iT!). PrEP iT! is grounded in the principles of the Technology Adoption Model and the Information, Motivation, and Behavioral Skills (IMB) model and includes virtual peer interaction and support, youth-centered PrEP and sexual health information, adherence reminders and self-monitoring, text message follow-up for youth whose adherence may be faltering, healthcare appointment reminders, healthcare provider interactions, and gamification components to optimize engagement. First, we will develop the PrEP iT! mobile intervention through focus groups with YMSM and refine iterations through input from a community advisory board (CAB). Four focus groups will be conducted to gain feedback on an existing mobile platform from which PrEP iT! will be adapted. Next, a CAB of YMSM will provide regular feedback during the iterative intervention design process. Usability testing with 6 members of the target population will be conducted, culminating in a final version of PrEP iT! Second, in preparation for a subsequent R01 trial, we will conduct a pilot randomized controlled trial to assess the feasibility, acceptability and preliminary impact of the PrEP iT! intervention for YMSM. Eighty YMSM recently initiating or restarting PrEP will be randomized to receive either PrEP iT! or usual care for 6 months, with biological and self-reported outcomes collected at baseline, and 3- and 6-month follow-up time points. Intervention use data will be collected to assess which intervention components impact study outcomes. Exit interviews of 10 YMSM will be conducted to further refine the intervention for a larger trial. PrEP iT! is innovative because it is the first intervention to use mobile phone technology to facilitate virtual peer support for YMSM on PrEP. The study advances PrEP science by addressing critical gaps (adherence & retention) in PrEP care among YMSM, and is sustainable because it will be built on an open source platform that may be integrated into clinical and community settings serving YMSM. If the PrEP iT! intervention is demonstrated to be effective, it may be quickly scaled up for wide-scale dissemination.

Abstract Among men who have sex with men (MSM), there is a resurgent epidemic of methamphetamine (meth) and other stimulant use that fuels new HIV infections and compromises the benefits of HIV treatment as prevention. Although MSM living with HIV who use meth can achieve viral suppression, prior research from our team and others has documented that recent stimulant use amplifies immune dysregulation in treated HIV infection. MSM living with HIV are also more likely to report amplified behavioral risk such as condomless anal intercourse that increases risk for HIV acquisition and onward HIV transmission. The scientific premise of this administrative supplement is that co-occurring meth and HIV will create a double jeopardy for the novel coronavirus (COVID-19) pandemic. In order to examine the potentially synergistic effects of meth and HIV for the COVID-19 pandemic, we will enroll 200 MSM in a seroprevalence study testing for IgM and IgG antibodies to the novel coronavirus (SARS-CoV-2). Using an intact groups design, participants will be enrolled based on meth use (user versus non-user) by HIV status (positive versus negative). Among men living with HIV, only those who report an undetectable viral load will be enrolled. Among men who are HIV-negative, only those who are not currently taking pre-exposure prophylaxis (PrEP) will be enrolled. There will be 50 participants enrolled per group: METH+HIV+, METH+HIV-, METH-HIV+, and METH-HIV-. The primary hypothesis is that those with co-occurring meth use and HIV (METH+HIV+) will display the greatest seroprevalence of SARS-CoV-2 relative to meth or HIV alone (METH+HIV- or METH-HIV+) or controls (METH-HIV-). We will also examine the extent to which co-occurring meth and HIV are indirectly linked to higher SARS-CoV-2 seroprevalence via alterations in gut-immune dysregulation, smoking behaviors, and decreased adherence to social distancing guidelines. This supplement will provide some of the first data regarding whether and how those with co- occurring meth use and HIV are more vulnerable to SARS-CoV-2 infection. This represents a crucial first step to identifying high priority populations that will directly inform the development bio-behavioral interventions to mitigate risk for COVID-19. These findings will also inform targeted public health efforts to ?flatten the curve? of community-level SARS-CoV-2 transmission in this rapidly evolving COVID-19 pandemic.

There is a strong resurgence of methamphetamine and other stimulant use in the United States (US). HIV- positive stimulant-using men who have sex with men (HIV+ SUMSM) may have greater difficulties navigating the HIV care continuum as well as display substantially elevated viral load (VL), amplified HIV transmission risk, and faster clinical HIV progression. While behavioral interventions show promise for achieving durable reductions in unsuppressed VL over time among HIV+ SUMSM, those residing outside of urban centers experience difficulties accessing services for HIV and substance use. For these reasons we propose a two-arm RCT of a 6-month mHealth intervention for HIV+ SUMSM, called Supporting Treatment Adherence for Resilience and Thriving (START). We will test the efficacy of START to improve VL suppression at 6 months (primary outcome) and determine whether any gains are maintained at month 12 (secondary outcome). START integrates two theoretically-grounded, evidence-based interventions (APP+ and ARTEMIS) with the goal of optimizing the effectiveness of treatment as prevention (TasP). HIV+ SUMSM (n=350) will be recruited and randomized to START or control to assess the following aims: Aim 1a. Test the efficacy of START for achieving a higher proportion of SUMSM who are virally suppressed at 6 months (primary outcome) compared to a website with referrals to HIV treatment information and substance use treatment resources (control condition). Aim 1b. Test the efficacy of START for maintaining viral suppression gains at 12 months, decreasing stimulant use and sexual risk, and increasing theory-based psychological processes (e.g., behavioral skills, positive affect). Aim 2. To assess the cost and cost-effectiveness of START, relative to the control condition, in achieving and/or maintaining viral suppression, including net savings with respect to averted healthcare utilization. During Phase I, we will integrate APP+ and ARTEMIS into a single START intervention platform using an iterative integration process that includes feedback through online focus groups with SUMSM. Phase I will conclude with usability testing among 10 HIV+ SUMSM to ensure a smooth transition to Phase II where we will conduct an RCT to test the efficacy of START. We will use home-based dried blood spot (DBS) collection to assess lab-quantified VL. All men will receive their respective condition for 6 months, with quarterly assessments until month 12. DBS specimens to measure VL will be collected at baseline, 6 and 12 months. The cost analysis will be framed from the provider perspective to estimate ?real world? costs of providing START to give stakeholders a sense of feasibility for broader implementation, given existing resources and reimbursement mechanisms. The proposed project is highly significant since optimizing TasP with HIV+ SUMSM is among the highest NIH and National HIV/AIDS Strategy priorities. START is innovative because it is scalable to reach a broader population of HIV+ SUMSM and may be adapted to clinic- and community-based settings.

There is a strong resurgence of methamphetamine and other stimulant use in the United States (US). HIV- positive stimulant-using men who have sex with men (HIV+ SUMSM) may have greater difficulties navigating the HIV care continuum as well as display substantially elevated viral load (VL), amplified HIV transmission risk, and faster clinical HIV progression. While behavioral interventions show promise for achieving durable reductions in unsuppressed VL over time among HIV+ SUMSM, those residing outside of urban centers experience difficulties accessing services for HIV and substance use. For these reasons we propose a two-arm RCT of a 6-month mHealth intervention for HIV+ SUMSM, called Supporting Treatment Adherence for Resilience and Thriving (START). We will test the efficacy of START to improve VL suppression at 6 months (primary outcome) and determine whether any gains are maintained at month 12 (secondary outcome). START integrates two theoretically-grounded, evidence-based interventions (APP+ and ARTEMIS) with the goal of optimizing the effectiveness of treatment as prevention (TasP). HIV+ SUMSM (n=350) will be recruited and randomized to START or control to assess the following aims: Aim 1a. Test the efficacy of START for achieving a higher proportion of SUMSM who are virally suppressed at 6 months (primary outcome) compared to a website with referrals to HIV treatment information and substance use treatment resources (control condition). Aim 1b. Test the efficacy of START for maintaining viral suppression gains at 12 months, decreasing stimulant use and sexual risk, and increasing theory-based psychological processes (e.g., behavioral skills, positive affect). Aim 2. To assess the cost and cost-effectiveness of START, relative to the control condition, in achieving and/or maintaining viral suppression, including net savings with respect to averted healthcare utilization. During Phase I, we will integrate APP+ and ARTEMIS into a single START intervention platform using an iterative integration process that includes feedback through online focus groups with SUMSM. Phase I will conclude with usability testing among 10 HIV+ SUMSM to ensure a smooth transition to Phase II where we will conduct an RCT to test the efficacy of START. We will use home-based dried blood spot (DBS) collection to assess lab-quantified VL. All men will receive their respective condition for 6 months, with quarterly assessments until month 12. DBS specimens to measure VL will be collected at baseline, 6 and 12 months. The cost analysis will be framed from the provider perspective to estimate ?real world? costs of providing START to give stakeholders a sense of feasibility for broader implementation, given existing resources and reimbursement mechanisms. The proposed project is highly significant since optimizing TasP with HIV+ SUMSM is among the highest NIH and National HIV/AIDS Strategy priorities. START is innovative because it is scalable to reach a broader population of HIV+ SUMSM and may be adapted to clinic- and community-based settings.

PROJECT SUMMARY In the US, Black women living with HIV/AIDS (WLHA) are less likely to be engaged in care, adherent to antiretroviral therapy (ART), and virally suppressed compared to White WLHA. Concurrently, Black women are also disproportionately affected by interpersonal violence ? physical, sexual, and/or psychological abuse by a current or former intimate partner or non-intimate partner ? which may co-occur with poor mental health and/or substance use disorders, further contributing to ART non-adherence, lower CD4 counts, and reduced viral suppression. Peer Navigation, while highlighted as a successful model of care in improving HIV care outcomes, requires resources that HIV service agencies often lack. A scalable and sustainable solution is the use of mobile health (mHealth) smartphone applications (?apps?). Although there has been an increase in mHealth interventions developed for HIV prevention and care among at-risk and HIV-positive MSM and youth, we are unaware of any to improve retention in care, ART adherence, and viral suppression among Black WLHA, nor any mHealth interventions that are responsive to Black women?s experiences with interpersonal violence. To address this gap, we will develop and pilot test a culturally tailored, trauma-informed smartphone app, called LinkPositively, for Black WLHA affected by interpersonal violence. Core components of LinkPositively include: a) Virtual Peer Navigation that includes phone and text check-ins and 4 weekly one-on- one video sessions to build skills to cope with barriers and navigate care; b) Social Networking platform to receive peer support; c) Educational and Self-care database with healthy living and self-care tips; d) GPS- enabled Resource Locator for HIV care and ancillary support service agencies; and e) ART self-monitoring and reminder system. Guided by the Theory of Triadic Influences and Syndemic Theory, the study will be conducted in 2 phases with corresponding aims. In Aim 1, 4 focus groups with Black WLHA with experiences of interpersonal violence, one focus group with peer navigators, and 4-6 key informant interviews with providers will be conducted to determine which app features, content, and functions are most likely to support downloading, initiating use, and sustaining engagement over time. Aim 1 will culminate in usability testing by Black WLHA affected by interpersonal violence (n=5), to finalize intervention components and procedures. In Aim 2, we will pilot test LinkPositively to assess feasibility and acceptability and determine preliminary effects of the intervention on HIV care outcomes (i.e., retention in care, ART adherence, viral suppression) and mechanism of change variables (i.e., social support, self-efficacy). Participants will be randomly assigned to either the intervention (n=40) or control (Ryan White standard of care, n=40) arm, with follow-up at 3- and 6- months. This study will benefit the advancement of HIV prevention science by harnessing technology to promote engagement in HIV care, while improving social support through peers and social networking ? all under the auspices of being trauma-informed for Black WLHA with experiences of interpersonal violence.