URBAN ARCH 4/5 Russia Cohort-Targeting HIV-comorbidities with Pharmacotherapy to Reduce Alcohol and Tobacco Use in HIV-infected Russians

PROJECT SUMMARY / ABSTRACTOver 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, andearly data indicate that COVID19 is associated with higher CVD risk. People living with HIV (PLWH) also haveincreased CVD risk compared to uninfected people and this risk is highest among those who arehazardous drinkers and smokers. Our research is designed to reduce CVD risk among these high riskPLWH and to elucidate key mechanism(s). St PETER HIV (U01AA020780) is a randomized controlled trial inSt. 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 associatedComorbidity 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 infectionand hazardous drinking both cause microbial translocation, which increases systemic inflammation and leadsto 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 gutfrom microbial translocation) and by extension alters the plasma metabolome (e.g., reduces plasmabutyrate levels) is unknown. Sparse data describe the prevalence of COVID19 among PLWH who are heavydrinkers and smokers, and no data exist assessing the association between COVID19 and biomarker levels ofinflammation and the plasma metabolome (e.g., butyrate) in this population. Our overarching hypothesis isthat COVID19 is a CVD risk factor among heavy drinking and smoking PLWH. For this application, wehypothesize that COVID19 infection will be: (1) common among St PETER HIV participants; (2) associatedwith 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 willleverage existing data from and collect new data among St PETER HIV and ACME 1/2 participants includingalcohol 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 itemsand testing, alcohol and smoking data, and inflammatory/metabolomic biomarker testing. We will leveragethese data to complete Aim 1: to describe and estimate prevalence of COVID19 infection in the St PETER HIVcohort; Aim 2: to determine the association between COVID19 infection and biomarkers of systemicinflammations; and Aim 3 (exploratory) to determine metabolic profiles among heavy drinking and smokingPLWH. Completing these aims will advance understanding of COVID19 effects on innate immune function andthe plasma metabolome. Results will inform future interventions targeting the GI microbiome among PLWH.