NIDA IRP Clinical Core support of the NIDA IRP HIV Clinical Program

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

The NIDA IRP HIV portfolio includes projects geared towards 1) reducing the incidence of HIV; 2) better understanding the link between HIV and substance use disorders (SUD); and 3) addressing HIV-associated comorbidities, coinfections, and complications. NIDA IRP HIV projects seeking to reduce the incidence of HIV and supported by the NIDA IRP OCD include HIV testing, counseling, and referral to treatment for research participation at the NIDA IRP. Another NIDA IRP HIV project supported by the NIDA IRP OCD is designed to reduce the incidence of HIV and address HIV comorbidities, coinfections, and complications. In 2024/2025, the Office of the Clinical Director (OCD), Intramural Research Program (IRP), National Institute on Drug Abuse (NIDA), NIH provides clinical research support to (6) independent Laboratories/Clinical investigators, (6 Senior Investigators/Branch Chiefs) and a Core/Facility Head. Details to specific HIV-focused support are detailed next. In one project, Dr. Thorsten Kahnt and team are investigating cognitive impairments persisting in people living with HIV despite anti-retroviral therapy, but these impairments remain under-characterized and it is unclear whether they include deficits in model-based control of behavior. HIV is common in people with substance use disorder (SUD) but the combined impact of HIV and SUD on cognition remains unclear. The olfactory system is uniquely vulnerable to neurodegeneration and overlaps with brain regions involved in decision making. This planned project will compare olfactory function and model-based behavior in people living with HIV and controls with and without a SUD, and relate these measures to biomarkers of neurodegeneration. In another project, Dr. Yihong Yang and team are investigating the combined impact of comorbid chronic cocaine exposure in people living with HIV (PLWH) on brain aging and neurocognitive impairment (NCI). A brain aging model was built based on network-wise cortical metrics in the brain MRI of Human Connectome Project in Aging using a machine learning approach. The model is going to be applied to a community cohort of HIV-infected and uninfected participants with or without cocaine use to predict their brain ages. Preliminary results show that both HIV infection and chronic cocaine use contribute to accelerated brain aging and increased risk of neurocognitive impairment, and chronic cocaine use further exacerbates neurobiological aging in PLWH. Dr. Yang and team are also conducting a project investigating whether cocaine use impacts HIV-related decision-making impairments through structural alterations in reward processing brain regions. An Iowa Gambling Task (IGT) is used to examine risk decision making and structural MRI is used to assess brain morphology. Decision-making parameters is derived using the Value Plus Persistence computational model through hierarchical Bayesian estimation. Structural metrics will be extracted using FreeSurfer, focusing on orbitofrontal cortex (OFC) and nucleus accumbens (NAcc), regions critically involved in reward and decision-making. Preliminary results show that cocaine use impacts HIV-related decision-making deficits through orbitofrontal cortex and nucleus accumbens alterations. Dr. Brenda Curtis and team are conducting a project that leverages national surveys and large-scale social media data to uncover emerging links between cannabis use, HIV risk, and PrEP adherence. By combining traditional epidemiology with novel social media analytics, this project is aimed at generating insights that lay the groundwork for personalized interventions. Dr. Leggio's Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section (a NIDA laboratory joint with NIAAA) is conducting two cohort studies to examine emerging pharmacotherapies (baclofen and spironolactone) and their potential health benefits for people living with HIV (PLWH), in addition to alcohol and other substance use disorder (ASUD) outcomes. For each study, the co-primary aims are whether the drug under investigation leads to 1) improvements in direct HIV-related biomarkers, i.e. decrease in HIV RNA levels and/or increase in CD4 count, 2) improved retention on antiretroviral therapy (ART), 3) improvement in liver function as measured by clinically relevant biomarkers of liver damage and function (FIB-4, AST, ALT, GGT, bilirubin, alkaline phosphatase, albumin, prothrombin time); 4) improvement in physical health (details below) and physiological frailty (VAC index); and 5) reduction in pain level. We will also examine whether the medication under investigation in each study leads to a reduction in alcohol drinking (as measured by the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C)) and/or a reduction in substance use disorder (SUD)-related outcomes (e.g., opioid use, incident opioid use disorder (OUD) diagnoses, and all cause hospitalization). The NIDA IRP OCD also supports a full-time Data Scientist / Biostatistician, whose roles include the development of IRB-approved secondary analyses related to the NIDA IRP HIV Portfolio that take full-advantage of the HIV-related data collected during the past 2 decades in the NIDA IRP. These efforts are currently under way and include exploratory and hypothesis-driven projects aimed at conducting cutting-edge work that will focus on the intersection between HIV risky behaviors, HIV infection, HIV-related comorbidities (e.g., HCV, liver diseases, etc.) and SUD. The NIDA IRP OCD also provides participant screening and support services for all HIV Portfolio study candidates. Furthermore, since 2022, the NIDA IRP OCD has worked to support community outreach, with a special emphasis on underserved populations. Of note, these are communities at higher risk of HIV and HIV-related comorbidities and complications. Important new efforts of the NIDA IRP Office of Clinical Director (OCD) are focused and re-directed in supporting the new revamped NIDA IRP HIV clinical portfolio by providing the necessary scientific, research, biostatistical (including data management and analysis), clinical, managerial, and administrative support and infrastructure necessary to start up and initiative the conductance of this quite significant new volume of clinical HIV projects in the NIDA IRP Clinical Portfolio. Dedicated clinical care and research support for these studies in the NIDA IRP HIV Portfolio is provided by the NIDA IRP OCD. Additionally, the NIDA OCD, through resources dedicated specifically to the NIDA IRP HIV Portfolio, supports all laboratory testing, radiology, consult, inpatient, and emergency care needs of all participants in NIDA IRP HIV Portfolio studies through a contract with Johns Hopkins. The NIDA IRP OCD provides human subjects protection and participant safety monitoring through human regulatory support, oversees the Data Safety and Monitoring Board (DSMB), the Intramural Research Program Auditing Committee (IRPAC), and assists clinical investigators with regulatory compliance support of the NIDA IRP HIV Portfolio. The NIDA IRP OCD also facilitates the advertising, outreach, and compensation efforts needed to generate unique specific advertising and recruitment materials for all potential candidates for NIDA IRP HIV Portfolio projects.