Cohort Studies of HIV/AIDS and Substance Use (U01 Clinical Trial Not Allowed)

The purpose of this Notice of Funding Opportunity (NOFO) is to support the continuation of NIDA's HIV Cohorts Program, encouraging existing and new sites to address new emerging and/or high priority research on multidisciplinary aspects of HIV/AIDS and substance abuse in alignment with NIH-HIV research priorities in order to inform policy or practice. Purpose The National Institute on Drug Abuse (NIDA) supports a program of longitudinal cohort studies that addresses the intersection of HIV and substance use. This program is a multidisciplinary platform to support basic, epidemiologic, and clinical research on HIV and HIV-associated co-morbidities and co-infections among populations with substance use and substance use disorders (SUDs) and to address research questions at the individual and population level. The purpose of this notice of funding opportunity (NOFO) is to support the continuation of NIDA's HIV Cohorts Program, encouraging existing and new sites to address new emerging and/or high priority research on multidisciplinary aspects of HIV/AIDS and substance use in alignment with NIH-HIV research priorities in order to inform policy or practice. Cohort sites supported under this program are required to report to and collaborate with a NIDA funded Coordinating Center, including participating in research agendas addressing NIDA’s high priority areas. Background Since the start of the HIV epidemic, cohort studies of people living with HIV (PLWH) and key populations at risk for HIV acquisition have made important contributions to the understanding of HIV virology, seroconversion dynamics, the natural and treated histories of HIV infection, the impact of HIV-associated co-morbidities (e.g., HCV) and complications including the role of substance use and SUDs. Longitudinal cohorts of at-risk individuals can provide crucial information about acute or early phases of infection, as well as disease transmission. Cohort studies provide a continuous source of data collection with the ability to address new or emergent public health problems, changes in drug use patterns and uptake of screening, prevention, or new treatments. Cohorts can also add to the understanding of processes such as aging, co-morbidities, social dimensions of HIV and substance use epidemics, as well as structural factors such as state and local policies, health insurance, and availability of relevant services. Research Objectives and Scope Research by each site should focus on high-risk populations or PLWH, who use substances. This RFA will seek applications from investigators working with HIV populations most affected by HIV (i.e., those at highest risk or living with HIV) in the United States. These can include sexual and gender minorities, racial/ethnic minorities, people involved in the criminal justice system and sex workers. Cohort populations should reflect social and economic characteristics of affected populations. Rural and metropolitan populations are welcome. This initiative also targets priority jurisdictions identified by the Ending the HIV Epidemic (EHE) initiative, although other jurisdictions will be considered with an epidemiologic justification (e.g., rural counties affected by opioid epidemics). Applicants must demonstrate the capacity to: Be responsive to changes to substance use and HIV epidemics, such as new substance use patterns, introduction of new substances; emergent co-morbidities including infectious diseases such as Mpox, COVID-19 and others, changes to public health policies, or to HIV/substance use treatments or prevention strategies. Applicants are strongly encouraged to include research that focuses on HIV-associated infectious co-morbidities (e.g., HCV, other sexual-transmitted disorders [STD]) and HIV-associated non-infectious co-morbidities, such as neurocognitive or other central nervous system impairment, mental health disorders and relevant medical disorders. [Note: The main focus of research should be the intersection of HIV and Substance Use, with co-morbidities as co-factors.] Partner with the end-user of the knowledge/data that would be generated (e.g., prevention specialists, Public Health officials, health departments, justice systems, policymakers, community organizations, etc.) and should thoroughly explain how the knowledge would be used to inform decisions and implement change. The involvement of the end-user is to ensure that the proposed data and methods will be useful. The partnerships with key end-users can be existing, or new relationships initiated based on success of previous stakeholder engagement and preparation to implement proposed work in a new setting. Collect data that can be used to inform policy and practice and include collaborations with potential end-users of cohort data such as those involved in HIV planning processes (e.g., EHE, Ryan White, CDC prevention funding) as well as service providers and provider organizations (e.g., health systems, federally qualified health centers [FQHCs], harm reduction sites). Participate in the collection of common data elements and biospecimens and participate in activities related to multi-site research such as data harmonization by working in concordance with the Data Coordinating Center. All sites are expected to collaborate and share all their data at least twice a year with the Data Coordinating Center. Assess variables that reflect system and structural factors that can affect HIV acquisition, utilization of prevention or treatment services, HIV viral suppression, substance use and/or factors that can influence dissemination of emergent prevention and care interventions. Research projects should address populations and research questions not captured by other HIV studies currently funded by NIH, including those co-funded by NIDA such as the WIHS/MACS Combined Cohort Study (MWCCS), the Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) or the NIAID Limited Interaction Targeted Epidemiology (LITE) cohorts while also being able to work with these outside cohorts on research questions where complementary of age, patterns of substance use, etc., may be desirable. Common Scientific Agenda and Collaboration with Data Coordinating Center: All sites are expected to collaborate and share all their data, at least twice a year, with the Data Coordinating Center at the University of Washington which will provide technical assistance, support, and resources. Clinical data and biological samples collected via the cohort(s) are expected to be available for sharing and use by the scientific community. Sites will also be expected to participate in collaborative activities including at least one annual meeting and monthly/quarterly conference calls with the Data Coordinating Center. Common Scientific Agenda All sites are also expected to participate in a common scientific agenda. The scientific areas listed below outline high priority research areas for NIDA that should be accomplished by each site during the five-year award period. There needs to be a clear justification of the clinical assessments, specimen collections, surveys and other measures, the frequency of participant visits and sampling from the cohort studies. Applications may propose additional research areas that are contemporary and are of high significance to the cooccurring HIV and substance use epidemics. Substance use and SUDs: drug use trends, types of drug use and frequency in relation to HIV risk and outcomes, risks associated with overdose related death HIV-related co-morbidities (HCV, Neurocognitive disorders) COVID-19; MPox and other sexually transmitted disorders), medical consequences, epidemiology, prevention, treatment, and outcomes in acute and chronic HIV Implementation: HIV and SUD services, uptake, and delivery. Point-of-care rapid testing, referral, and treatment, geocoding HIV viral loads: in relation to substance use, treatment, and co-morbidities Treatment: HIV and SUD treatment uptake and adherence, linkage to care Social determinants of health: socioeconomic factors, social support, trauma/violence, stigma, discrimination, life transitions, and food insecurity and the mechanisms of action through which they may affect health outcomes among people living with or at risk of HIV acquisition Brain and CNS: behavioral and psychiatric abnormalities, neurocognitive alterations in the context of substance use and HIV Genomic and phenotypic data in the context of HIV, co-morbidities, and substance use Research Strategy: Sites funded under this RFA will serve as a national resource for research addressing the intersection of HIV and substance use in the United States. Applications should include multidisciplinary teams and should select key populations at risk for HIV acquisition or populations of PLWH. Variables should reflect substance use in the study population with particular attention to its relevance for HIV acquisition, transmission, response to HIV treatment and/or viral suppression. Studies should address variables related to policy and practice such as HIV, substance use and other health care/public health service utilization, health insurance, key HIV risk populations and PLWH, people who experience marginalized social and sexual identities. Data collection should address stigma and discrimination as well as resource constraints (e.g., food, shelter, access to reliable transportation, access to reliable and private internet connectivity), particularly those which may limit participation in public health or health care services. Data collection should reflect current best clinical and methodologic practices and can include biospecimen collection, behavioral data from surveys or interviews, electronic health records and other methods that are consistent with study aims and objectives. The research strategy should include collaborations with potential end-users of cohort data such as those involved in HIV planning processes (e.g., EHE, Ryan White, CDC prevention funding) as well as service providers and provider organizations (e.g., health systems, FQHCs, harm reduction sites) or others (prevention specialists, Public Health officials, health departments, justice systems, policymakers, community organizations, etc.). Applications must thoroughly explain how the knowledge/data would be used to inform decisions, policy, practice and/or implement change. Applications need to address NIH and NIDA’s highest priority areas of research: Research Priorities | NIH Office of AIDS Research NIDA HIV Priority Areas Sites should consider their capacity to address areas of interest such as the following: System and structural level factors that lead to HIV acquisition Social determinants of HIV and substance use, including factors that increase exposure to HIV and substance use New or emerging substance use patterns and recovery approaches Long-term HIV/substance use outcomes and medical consequences such as those associated with aging and HIV Capturing the effects of systemic interventions to increase prevention, diagnosis, and treatment, including differences in HIV testing service, utilization, etc. that occur in different settings such as community organizations, FQHCs, and health systems. In addition, sites are strongly encouraged to: Expand existing populations: Increasing the representation of PLWH, ensuring the representation of sexual and gender minorities, ethnic/racial minorities and people with lived experiences, factors that contribute to HIV risk and poor treatment outcomes such as homelessness, engaging in sex work, and criminal justice involvement. EHE priority jurisdictions should be addressed in the application with epidemiologic justification provided for non-EHE jurisdictions such as rural areas affected by opioid epidemics. Demonstrate their capacity to recruit and follow populations of adequate sample size and power (i.e., >500). Smaller sample sizes need justification with respect to local epidemiology and factors such as population and service density. Sites with established cohorts should demonstrate their capacity to, and describe plans to, refresh samples and continue to recruit participants and comply with the NIH data sharing policy. The Research Strategy should: Describe how substance use in the population will be characterized i.e., specific drugs used, level and history of use, form of administration, continuum cascade of substance use, and/or changing patterns over time including initiation. Describe methods for the recruitment, enrollment, and retention of cohort participants, describing previous experience with recruitment and retention of longitudinal samples. Describe the data collection methods and their appropriateness for the variables of interest, as well as the primary analyses of data, providing a rationale for the analytic methods selected and the statistical power for major analyses. Include specific proposed data elements, such as clinical data, summary health histories, biologic specimens, socio-behavioral data, or treatment variables that will support the study aims Given the requirement of data sharing across cohort sites, the discussion should address how proposed data elements could incorporate common or shared platforms. Provide justification of the priority research domains for the cohort study and for the approaches to achieving the study aims. The study rationale should indicate how the cohort will address gaps in current NIH-funded HIV cohort research (e.g., MWCCS, CNICS, LITE) and indicate where it might complement existing cohort research. Describe experience with participation in multi-site research, particularly where data sharing was integrated into the research. Applications also should describe the administrative and organizational structure for the project and how it will facilitate attainment of the aims and objective of the proposed research. Where biospecimens are routinely collected, applications should describe procedures for processing, storage, and sharing for use by the scientific community. Document alignment with EHE plans or other appropriate HIV service plans (e.g., CDC/Ryan White planning processes) and provide a plan for engaging local decision makers, as well as document how cohort data can inform local decisions about resource allocation and service delivery. For renewal applications, applicants should provide a rationale for continued funding including information regarding any new data collection. Renewal applicants must provide plans to demonstrate program relevance and to ensure representation of current HIV/substance use epidemic patterns. Applications Not Responsive to this NOFO include: The following types of applications will be considered non-responsive and will be returned without review: Studies that do not have the capacity to adhere to data sharing requirements and data harmonizing activities with the data coordinating center (transferring data, common data elements or biorepository data sharing) as specified above. Studies with less than 500 participants without adequate justification. Applications with a primary focus on research related to end organ or systemic disease related to comorbidities such as cardiac, liver, or chronic kidney diseases, hypertension, and bone disorders. Studies that do not focus on HIV infection and substance use and/or outcomes. Plan for Enhancing Diverse Perspectives (PEDP) This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP) as described in NOT-MH-21-310, submitted as Other Project Information as an attachment (see Section IV). Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material. The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.