Genomics and Epigenomics of HIV/AIDS and Substance Abuse

United States

Purpose:

Define priorities for genomics-related research in HIV/AIDS and substance abuse, identify existing clinical and technical resources as well as new resources needed that would allow researchers to address these priorities, and recommend solutions to challenges in pursuing these goals.

Topics Discussed:

• What are the most critical research questions and approaches for genomics and epigenomics research in HIV/AIDS and substance abuse?
• What populations, data sets, and samples are available for use or can be built upon to address these priorities, and what genetics and genomics approaches will be most useful?
• What are the challenges in genomics research related to HIV/AIDS and substance abuse, and how can these challenges be overcome?

Fundamental Take-Home Messages from Talks/ Group Discussions:

• NIDA should support science that first addresses critical and unanswered questions in the HIV field, and then examine the impact of substance use on those findings. Although model systems (e.g. non-human primates) can be useful additions to these goals, NIDA should focus less on artificial systems that examine potential interactions between drugs of abuse and HIV but do not clearly demonstrate potential clinical impact. Examples of important research areas to pursue include:
  • Host and viral genetic factors affecting HIV susceptibility or specific disease progression phenotypes (e.g., long term non-progressors vs. rapid progressors, neuroAIDS, viral evolution) in the era of combined antiretroviral treatment and the effects of distinct patterns of substance use;
  • Genetic/epigenetic basis of innate and adaptive immune response variation in specific tissues/cell types as related to disease outcomes, and impact of substance use on these responses
  • Development of tools (e.g., molecular imaging) to analyze and measure of latent viral pools, and effects of substance use on molecular/epigenetic regulation of HIV latency and reactivation
  • Impact of nonstructured antiretroviral treatment interruption (e.g., due to substance use relapse) on viral and host factors related to disease outcome
• To better leverage existing resources, NIDA should work with OAR, NIAID, and other ICs to make cohort and clinical study data more accessible (e.g. develop and interactive database), to simplify data sharing and access to multiple databases, and to work toward harmonization of data sets by establishing standardized terminology and sequence analysis methodologies.
• NIDA should help determine what substance use assessment tools would be meaningful and useful yet straightforward to incorporate into ongoing clinical HIV studies.
• NIDA should hold workshops and find additional ways to stimulate effective collaboration among clinical and basic HIV/AIDS researchers, substance abuse experts, systems biologists, computational biologists, and population geneticists.
• NIDA should work with OAR, NIAID and NCI to determine if the AIDS Reagent Bank could be expanded to be a more comprehensive resource for high quality biological resources.