PROJECT SUMMARY / ABSTRACT Over 4,000,000 people worldwide are infected with COVID19 and cases are rising. Acute respiratory infections (e.g., Severe Acute Respiratory Virus), are associated with increased cardiovascular disease (CVD) risk, and early data indicate that COVID19 is associated with higher CVD risk. People living with HIV (PLWH) also have increased CVD risk compared to uninfected people and this risk is highest among those who are hazardous drinkers and smokers. Our research is designed to reduce CVD risk among these high risk PLWH and to elucidate key mechanism(s). St PETER HIV (U01AA020780) is a randomized controlled trial in St. Petersburg, Russia comparing the effects of nicotinic partial agonists on alcohol consumption, smoking, and inflammation and CVD risk among PWLH who are heavy drinkers and smokers. The Alcohol associated Comorbidity and Microbiome Evaluation (ACME ½ U01AA026222) study, nested within St PETER HIV, examines the gut microbiome as a novel pathway for increased CVD risk among these PLWH. HIV infection and hazardous drinking both cause microbial translocation, which increases systemic inflammation and leads to CVD. Whether COVID19 co-infection among PLWH who drink and smoke increases inflammation, alters the gut microbiome (i.e., reduces beneficial butyrate-producing bacteria which protect the gut from microbial translocation) and by extension alters the plasma metabolome (e.g., reduces plasma butyrate levels) is unknown. Sparse data describe the prevalence of COVID19 among PLWH who are heavy drinkers and smokers, and no data exist assessing the association between COVID19 and biomarker levels of inflammation and the plasma metabolome (e.g., butyrate) in this population. Our overarching hypothesis is that COVID19 is a CVD risk factor among heavy drinking and smoking PLWH. For this application, we hypothesize that COVID19 infection will be: (1) common among St PETER HIV participants; (2) associated with increased inflammation (e.g., higher IL-6); and (3) associated with an unfavorable metabolomic profile (i.e., lower plasma butyrate) as compared to those not infected with COVID19. To test our hypotheses, we will leverage existing data from and collect new data among St PETER HIV and ACME 1/2 participants including alcohol measures using the timeline follow-back; biomarkers of inflammation, data on comorbid conditions, longitudinal stored blood and fecal samples and imaging data. New data will include: COVID19 survey items and testing, alcohol and smoking data, and inflammatory/metabolomic biomarker testing. We will leverage these data to complete Aim 1: to describe and estimate prevalence of COVID19 infection in the St PETER HIV cohort; Aim 2: to determine the association between COVID19 infection and biomarkers of systemic inflammations; and Aim 3 (exploratory) to determine metabolic profiles among heavy drinking and smoking PLWH. Completing these aims will advance understanding of COVID19 effects on innate immu...