2022-2026 NIDA Strategic Plan
Priority Scientific Area #3: Accelerate Research on the Intersection of Substance Use and HIV

Substance use plays a significant role in HIV transmission and health outcomes for people living with HIV. The opioid crisis has been associated with marked increases in the number of people who inject drugs in the United States. This has resulted in several localized HIV transmission hot spots, driven by risky injection practices, poor support for syringe exchange programs, and limited access to OUD treatment. In addition, the resurgence in the use of psychostimulants, including methamphetamine, is associated with high-risk sexual behaviors that increase HIV infection. 

NIDA has long recognized the intertwined nature of substance use and HIV and for decades has supported innovative and multidisciplinary research in this area through traditional funding mechanisms, and through the Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research and the Avenir Award Program for Research on Substance Use Disorders and HIV/AIDS, to drive exceptional research. These mechanisms encourage cutting-edge, high-risk, high-payoff research with the potential to open new avenues of science and/or lead to breakthroughs in HIV/AIDS prevention and treatment interventions for people using drugs.

This work has led to significant scientific advances, including a seminal study demonstrating that scaling up HIV treatment in people who inject drugs results in reductions in community-level viral load and HIV transmission, and the finding that addiction treatment, especially medications for OUD, is a necessary part of HIV care for those with SUDs and leads to reduced viral load, increased infection-fighting CD4 cell count, and greater retention in HIV care. 

Despite scientific advances, rates of HIV in the United States and globally remain unacceptably high. Additional research is needed to understand the relationship between HIV, substance use, and SUD. This includes research to improve surveillance of HIV and its relation to drug use practices; mechanistic studies to determine how substance use affects HIV transmission and progression; development of combination therapies for HIV and SUDs; and identification and implementation of strategies scaling up evidence-based interventions, including SSPs and improved access to medications for OUD and HIV in diverse settings. 

Goal 3.1: Increase understanding of the etiology, pathogenesis, spread, and persistence of HIV/AIDS among people who use drugs

It is imperative to identify mechanisms by which drug use interacts with HIV to affect disease progression and pathology. For example, while HAART has reduced the prevalence of HIV-associated dementia, milder forms of neurological complications occur in people living with HIV, and emerging evidence suggests a relationship between drug use and accelerated or more severe nervous system complications in the presence of HIV. We also know that inflammation and immune activation are consequences of drug use and key drivers of neurological disorders and psychiatric comorbidities linked to HIV. Both HIV and HAART have been shown to alter gut microbial composition and thereby influence inflammation and immune activation in HIV-infected individuals. NIDA is focused on expanding knowledge to better understand how drug use, SUDs, HIV, HAART, and treatment for SUDs impact neuroinflammatory processes. Such research has the potential to yield new therapeutic targets and enhance treatment outcomes in people living with HIV and SUDs.

NIDA also encourages research in the areas of systems biology, epigenomics, nucleomics, and transcriptomics to address important questions related to mechanisms of HIV persistence in the presence of drug use or SUDs. Little is known about the impact of drug use on HIV reservoirs, including how drugs modulate epigenetic mechanisms that regulate HIV latency in the brain and lymphoid tissue, making this an important area of investigation. These efforts can provide foundational knowledge for the development of strategies to effectively treat or cure HIV/AIDS in people using drugs. Novel approaches are also needed to develop HIV and SUD drugs that can cross the blood-brain barrier and reach brain targets.

Key Focus Areas

  • Assess the role of drug use in HIV infection and pathology in the central nervous system.
  • Determine how drug use or substance use therapies interact with HIV and HAART to affect inflammation and immune responses.
  • Elucidate mechanisms by which drug use affects HIV latency.
  • Use basic science findings to guide therapeutic strategies.
Goal 3.2: Prevent new infections and transmission of HIV among people who use drugs and their sexual and/or injection partners

People who inject drugs are more likely to be living with HIV compared with the general population. Indeed, Joint United Nations Programme on HIV and AIDS UNAIDS data based on relative HIV incidence in the global population indicate that people who inject drugs are 22 times more at risk for acquiring HIV.  In the United States, the federal End the HIV Epidemic (EHE) initiative includes priorities for expanding evidence-based strategies for HIV prevention and treatment, which are critical for reducing the spread of HIV among people who use and/or inject drugs. The use of HAART—such as tenofovir/emtricitabine—by people who are at elevated risk but do not have HIV is an effective primary prevention strategy for reducing the transmission of HIV. However, little is known about the use of PrEP by people who use drugs; therefore, developing evidence-based primary and secondary prevention strategies to avert HIV acquisition in this population is a key priority. This includes research to understand the acceptability and access to PrEP among people who use drugs; the extent to which health care providers prescribe PrEP to at-risk people who use drugs; how drug use affects PrEP adherence; how to integrate PrEP into substance use treatment and harm reduction programs; and the feasibility and impact of new long-acting PrEP.

The idea of “treatment as prevention” is an important component of secondary prevention strategies. When people living with HIV are on antiretroviral treatment with an undetectable viral load, they have a negligible risk of transmitting HIV to their partners. This awareness informed a HIV care cascade model to facilitate testing, treatment, retention in care, and viral suppression—a model that has also been applied to OUD. Despite evidence that providing HIV and SUD treatment impacts HIV incidence at a population level and enhances the care cascade for people with SUDs, barriers to implementation remain. Moving forward, research approaches will need to focus on developing personalized treatments that meet the needs of patients; retaining and re-engaging people in HIV and SUD care; ensuring that antiretroviral therapy and SUD treatment (including MOUD) are available immediately upon diagnosis; reducing provider stigma, which marginalizes individuals and prevents treatment seeking and retention; and addressing unequal access to treatment to eliminate health disparities. Research is also needed to bring effective interventions to scale across settings where they will be most impactful. NIDA will continue supporting research to support EHE domestically and eliminate HIV transmission globally.  

Key Focus Areas

  • Improve access to PrEP and emerging prevention interventions.
  • Optimize HIV and substance use care cascades—especially those associated with EHE.
  • Develop strategies for reducing stigma by health care providers against people with HIV who use drugs.
  • Develop strategies to integrate and scale HIV and SUD care in justice settings and to ensure continued care after transition back to the community.
  • Develop approaches to expand HIV and SUD care into hard-to-reach areas, such as rural settings, where access to care is limited.
Goal 3.3: Address comorbidities and improve health outcomes among people living with HIV who use drugs

SUDs and HIV frequently co-occur with HCV, psychiatric conditions, COVID-19, and other conditions, and research is needed to develop an evidence base for understanding and addressing these comorbidities. 

NIDA continues to foster basic research to identify mechanisms that underlie HIV-related comorbidities and use this information to develop therapies that improve the lives of people living with HIV who use drugs. For example, a better understanding of the relationships among comorbid conditions may point to shared biological substrates, environmental influences, and social conditions that could become targets for intervention. As therapeutics for SUDs, HIV, and HCV are developed, testing for interactions between these medications and addictive drugs is important to understand the impact of drug use on HIV/HCV progression, determine drug-drug interactions, and ensure the most effective combination therapy approaches. 

Additional research is also needed to determine how best to provide high-quality, integrated care to address drug use, SUDs, HIV, and other comorbidities. Integrated care models are needed to enhance the adoption and integration of effective SUD treatment, including screening, MOUD, and smoking cessation, into HIV care settings. Likewise, research is needed to increase the adoption and integration of effective HIV treatment (including linkage and long-term retention in HIV care) in substance use treatment settings. In both HIV and addiction treatment settings, research is needed to enhance the adoption and integration of treatment services to identify and address other common comorbidities. Organizational and systems-level interventions, and implementation science, can also develop generalizable approaches to deliver integrated care in other settings, including primary care and other general medical settings, mental health care settings, Federally Qualified Health Centers, and the justice system. Finally, developing effective ways to modify social determinants of health are needed to fully address HIV, substance use, and co-occurring conditions.

Key Focus Areas

  • Identify common underlying mechanistic substrates for neurological comorbidities.
  • Understand interactions of drug use, HIV/AIDS, HCV, and medications used in treatment.
  • Elucidate mechanisms by which drug use affects clinical outcomes in HIV, including progression and mortality.
  • Develop integrated models to address SUDs, HIV, HCV, and other comorbidities in multiple health care and community settings.