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Impact of Methamphetamine Use on the HIV Nucleome in individuals on Antiretroviral Therapy

A major challenge in ending the HIV pandemic is the persistence of the latent HIV reservoir that can lead to viremia, disease progression and transmission to new hosts after discontinuation of antiretroviral therapy (ART). Efficient treatment regimens that successfully eliminate cell populations carrying intact proviruses are not available due to the incomplete understanding of the cellular mechanisms that allow the virus to remain quiescent within the host genome. A compounding risk factor in HIV pathology is substance use disorder (SUD) known to contribute to decreased adherence to and delay of viral decay due to ART, and accelerated progression to AIDS. We hypothesize that persistence of HIV reservoirs is encoded in the proviral location within the 3D architecture of the host genome (nucleome), and influenced by SUD-induced changes in epigenetic structures.

A major barrier to developing a cure for AIDS is the ability of the HIV-1 provirus to stay dormant in the host cell. Information about the genomic sites that harbor proviral DNA and the influence that addictive substance abuse exerts on latent HIV-1 will be essential for the development of novel approaches to curative AIDS treatments. This exploratory high risk/high pay off approach exploits information about genomic structures to understand mechanisms of HIV-1 reservoir maintenance.

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08/15/2018 to 05/31/2021
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