Association Between Viral Hepatitis Infection and Low Muscle Mass Among HIV-Positive Individuals



 DESCRIPTION (provided by applicant): This award will provide the applicant with important skills necessary for her continued development as an Infectious Diseases epidemiologist, with a focus on nutritional and clinical outcomes of viral hepatitis in HIV- infected persons. The proposed training plan includes: 1) advanced epidemiologic coursework at the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; 2) mentorship from successful researchers in HIV, viral hepatitis and nutrition; and 3) collaboration with investigators from two ongoing HIV cohort studies. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are highly prevalent among individuals with HIV, and accelerated disease progression from viral hepatitis contributes to the morbidity and mortality observed in these patients. Identifying mechanisms underlying the accelerated disease progression and adverse outcomes in coinfected patients is critical to developing targeted therapeutic strategies. Malnutrition in HIV-infected patients has been shown to be an independent risk factor for poor health outcomes, with loss of peripheral muscle mass often an initial indicator of poor nutrition. Importantly, coinfection with chronic viral hepatitis may also induce adverse changes in a patient's nutritional status and further contribute to the development of low muscle mass, apart from HIV and prior to the onset of hepatic decompensation. Thus, low muscle mass may be an important mediator of poor health outcomes among individuals coinfected with viral hepatitis and HIV. However, there are few data on the occurrence of low muscle mass in these patients. To begin to close the knowledge gap, this proposal seeks to: 1) determine if HBV or HCV infection is associated with low muscle mass among HIV-infected patients; and 2) identify risk factors for low muscle mass in coinfected patients. It is hypothesized that coinfected patients wil have a higher prevalence of low muscle mass compared to HIV-monoinfected and uninfected persons. Potential risk factors for low muscle mass include hepatic inflammation, HIV disease severity, substance use, metabolic syndrome and/or chronic kidney disease. The aims will be accomplished through a cross-sectional analysis within the Women's Interagency HIV Study and Multicenter AIDS Cohort Study, both of which are ongoing, prospective cohorts of HIV-infected persons. An association between viral hepatitis and loss of muscle mass would indicate that clinicians should screen coinfected patients for low muscle mass. This work will have important public health impact by identifying modifiable host factors that may improve survival outcomes among HIV/viral hepatitis-coinfected patients, particularly in resource-constrained settings with limited access to antiviral therapy or transplantation. Upon completion of these aims, the principal investigator will have advanced understanding of the nutritional impact of viral hepatitis and be poised to make further substantive contributions in viral hepatitis and nutritional epidemiology.