The majority of human immune deficiency virus 1 infected patients in the US are on long-term (10+ years) combination antiretroviral therapy (cART). While cART suppresses HIV replication to below 50 copies/ml, not much is known about the long-term effect of cART on Kaposi sarcoma associated herpesvirus (KSHV) oral transmission, oral and systemic KS disease or the latent KSHV reservoir. We propose to investigate the impact that different cART components have on KSHV and KS disease with the long-term aim to interrupt oral KSHV transmission and cure the virus from persons living with HIV/AIDS. Specifically, we will focus on modulating the reactivation of KSHV and how cART drugs affect KSHV exosomes/ extracellular vesicles. This is a competitive renewal application in response to PA-16-426/ High or Medium Priority AIDS Research on Non-AIDS-defining or AIDS-defining Cancers (R01).
Kaposi Sarcoma and Kaposi-Sarcoma-associated herpesvirus are ?high priority HIV-associated comorbidities, coinfections, and complications? as defined in NOT-OD-15-137. The research is relevant to public health as Kaposi Sarcoma, including in the oral cavity, is among the most common AIDS-associated morbidites in the era of cART in the US and LMIC around the world with still incomplete cART coverage. As KSHV is transmitted by saliva, understanding KSHV biology is central to the mission of NIDCR; this proposal utilizes biospecimens generated by the NIDCR-sponsored Oral HIV/AIDS Research Alliance (OHARA).
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