LSUHSC CARC RC4: Alcohol and HIV-associated cancer pathogenesis Chronologic aging and alcohol use are established contributors to cancer progression in persons living with HIV/AIDS (PLWHA). However, clinical relationships and synergistic mechanisms for alcohol and oncogenic herpesviruses, including the Kaposi's sarcoma-associated herpesvirus (KSHV), have not been established. KSHV is the etiologic agent for Kaposi's sarcoma (KS) - the most common tumor in the general population in geographic areas where HIV and KSHV infection are highly co-prevalent. KS has also been recognized with increasing frequency in patients on effective antiretroviral therapy (ART), and survival remains limited for those with advanced disease. Greater KSHV replication incurs an increased risk of onset and progression for KS, but there are currently no viable long-term approaches in the clinic for reducing KSHV replication. Reduced glutathione (GSH) is markedly depleted with oxidative stress, which is enhanced by chronic alcohol consumption in PLWHA. We have reported that oxidative stress facilitates KSHV pathogenesis, and others have demonstrated a role for oxidative stress and GSH depletion in KSHV+ tumor progression in vivo. Therefore, we hypothesize that oxidative stress resulting from chronic alcohol use in PLWHA facilitates KSHV infection and/or replication, thereby increasing risk for KS incidence and progression. Recent screening of a minority-predominant cohort of PLWHA from the HOP Clinic has revealed high prevalence for alcohol use disorders (AUD), KSHV seroprevalence rivaling hyperendemic regions in Africa, and plasma signatures indicating significantly increased oxidative stress relative to HIV-uninfected individuals. We propose to determine whether alcohol use associates with KSHV seroprevalence and oxidative stress in PLWHA in cross-sectional studies, and whether changes in the patterns of alcohol consumption over time impact KSHV replication and oxidative stress in a longitudinal cohort. These studies are critical for defining specific alcohol use assessments and novel bioassays to identify patients with AUD at high risk for virus-associated cancers despite effective ART. We anticipate that these data will provide rationale for future clinical trials evaluating alcohol use interventions and/or pharmacologic reduction of systemic oxidative stress as tools for cancer prevention in PLWHA and AUD. The technically advanced approach for quantifying systemic oxidative stress will also contribute to novel research by other CARC investigators related to the mechanistic basis and consequences of alcohol-induced oxidative stress which disproportionately impact minority-predominant PLWHA.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
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Louisiana State Univ Hsc New Orleans
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