NIDA research is advancing progress against HIV

Studies at the intersection of HIV and substance use can shape prevention, treatment, and care.

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The HIV epidemic is so entwined with the crisis of drug addiction that they are sometimes referred to as a syndemic. Drug intoxication can impair judgment and increase impulsivity, raising the risk of exposure to situations associated with HIV acquisition and transmission.  Drug use can also weaken immune function and interfere with health care engagement—factors that together accelerate HIV transmission and disease progression. Recent HIV clusters in the United States have consistently been associated with overlapping structural, social, and health-related factors—including housing instability, psychosocial stressors, limited access to care, and injection drug use, highlighting the complex realities faced by people navigating multiple barriers to care.

NIDA is one of the largest funders of HIV research at NIH, supporting research across the continuum of basic to implementation science. This work has had significant impact. It was NIDA-funded science two decades ago that established the importance of medications for opioid use disorder and other addiction treatment as an essential component of HIV care for people living with substance use disorders (SUDs). Subsequent NIDA-funded research demonstrated the principle of HIV treatment as prevention: Greater delivery of HIV treatment in people who inject drugs led to reduced HIV viral load and transmission in the community.

The intersection of HIV and substance use continues to shape research priorities at NIDA. One of these priorities is to create bridges across the research continuum that can advance effective, evidence-based HIV and substance use interventions across biological, clinical, and structural levels.

An example of one such project is the SCORCH program (Single Cell Opioid Responses in the Context of HIV), which represents a major investment in cutting-edge neuroscience, leveraging single-cell genomics to map how HIV infection and SUDs—particularly opioid, methamphetamine, and cocaine use disorders—alter brain function at the level of individual cell types. By generating and openly sharing large-scale transcriptomic and epigenomic datasets, SCORCH enables researchers worldwide to identify the specific cellular pathways through which drugs and HIV interact, including mechanisms that may drive viral persistence, neurocognitive impairment, and addiction. This work is revealing potential targets for new therapies that could simultaneously address addiction and HIV-related brain complications while also establishing a shared scientific infrastructure built on FAIR (findable, accessible, interoperable, reusable) data principles to accelerate discovery across disciplines and institutions.

A recent SCORCH study by a team at Icahn School of Medicine at Mount Sinai illustrates just how powerful this approach can be in uncovering the biological linkages of substance use and HIV. Using single-cell sequencing of human brain tissue, investigators were able to examine how individual brain cell types, particularly dopamine-producing neurons and microglia, are altered in people with HIV and SUDs. They found that while neurons themselves are not directly infected by HIV, they show significant changes in gene activity related to stress, inflammation, and signaling, suggesting that the virus indirectly disrupts brain function. At the same time, microglia—the brain’s resident immune cells and a key site of HIV persistence—show heightened inflammatory and immune responses, which can contribute to ongoing neural injury and may help sustain viral reservoirs in the brain. 

Importantly, the study also found that substance use can amplify many of these same pathways, particularly those related to neuroinflammation and cellular stress, pointing to overlapping biological mechanisms through which HIV and drugs like opioids or cocaine jointly affect the brain. HIV and drugs interact within specific populations of neurons in ways that can worsen cognitive impairment, reinforce addiction-related circuitry, and complicate treatment and long-term health outcomes. These findings are significant because they move us beyond broad observations to precise, cell-level insights, helping identify new targets for therapies with potential to reduce brain inflammation, protect neural function, and disrupt HIV persistence in the central nervous system.

Ensuring that evidence-based interventions are effectively implemented and sustained in real-world settings is a major priority across NIH. Effective HIV prevention and treatment strategies must account for the full context of people’s lives, including behavioral health, social conditions, relationships, and access to supportive care. Complementing SCORCH’s basic science efforts, the CONNECT program (Collaborative Network to End the HIV Epidemic and Address Addiction in the Criminal Justice System) focuses on how we deliver SUD and HIV care to one of the populations facing disproportionate barriers to HIV and SUD care. People involved in the criminal justice system experience high rates of SUD and elevated risk for HIV, yet they often face fragmented care, particularly during transitions such as community reentry—a period associated with heightened vulnerability and disruptions in continuity of care. The criminal justice system also represents a critical point of engagement for people who may face barriers to accessing healthcare. Launched in 2024, CONNECT is developing and testing scalable models that integrate prevention, diagnosis, and treatment with evidence-based SUD services across criminal justice and community settings. These models address core implementation challenges related to engagement, continuity of care, and coordination across systems.  

Designed to bring together researchers, service providers, people with lived and living experience with HIV, SUD, and/or the criminal justice or legal system, and partners across the criminal justice system to improve how we deliver HIV and substance use disorder services for people involved in the criminal justice system, CONNECT includes ten interconnected awards: eight academic regional research hubs conducting multisite hybrid implementation-effectiveness clinical trials across diverse, high-burden communities; a data coordination and dissemination center that supports collaboration, data harmonization, and translation of findings into practice; and a patient engagement resource center that ensures research is informed by the lived and living experiences of people most affected. Together, these components will generate actionable, community-informed evidence on how to expand access to medications, behavioral interventions, digital tools, and patient-centered care within criminal justice settings, while also building the infrastructure and partnerships needed to sustain these efforts. By aligning science, systems, stakeholder engagement, and community partnerships, CONNECT is helping lay the groundwork for more effective and equitable delivery of HIV and SUD services nationwide.

It is also crucial to build the pipeline of next-generation research in the HIV-drug addiction space. NIDA supports early-career investigators working at the intersection of HIV and SUDs through coordinated funding, training, and workforce development initiatives designed to foster innovation and strengthen the future research workforce. Among those is our Avenir Award Program for SUDs and HIV, which supports exceptionally creative new and early stage investigators. The three Avenir-award-winning projects in 2025 focused on developing and implementing innovative, real-world strategies to expand access to integrated HIV and SUD care for high-risk, underserved populations—particularly those in safety-net, community, and criminal justice system settings. 

Ending the HIV epidemic will require coordinated, integrated approaches that simultaneously address HIV prevention and treatment, substance use disorders, and the structural and behavioral factors that contribute to HIV risk. By integrating biological, behavioral, and systems-level research, NIDA is working to better understand the intersection of substance use and HIV and to translate that knowledge into more effective, equitable strategies to prevent HIV transmission and improve outcomes for populations disproportionately affected by HIV and substance use.