Mentoring Research in Non-infectious Complications of HIV

Abstract The goals of this application for a K24 midcareer investigator award in patient-oriented research (POR) are to allow me to devote more time to augment capabilities in POR with a focus on non-infectious complications of HIV, and provide mentorship to junior investigators. With an aging population of people with HIV (PWH), research on prevention and management of non-infectious complications of HIV will continue to increase in importance. I am an infectious diseases specialist trained in epidemiology whose research has primarily focused on elucidating the impact of HIV and antiretroviral therapy (ART) on bone health. I have established multidisciplinary collaborations over the last 15 years to evaluate the epidemiology of bone loss, osteoporosis and fractures in PWH, determine the impact of perinatal HIV on bone acquisition and peak bone mass, and perform clinical trials to mitigate bone loss with ART. I have also led translational studies using novel imaging and biomarkers to investigate pathogenic mechanisms; however, these mechanisms are still not completely understood, largely due to lack of tissue-based studies. Biospecimens from recently completed studies, including the comprehensive first bone biopsy study of PWH before and after ART initiation and a study of women undergoing the menopausal transition (RO1 AI095089) provide new opportunities for mechanistic insights. The Specific Aims of the Research Plan are to: (1) investigate the pathophysiologic underpinnings of impaired bone formation associated with HIV and ART through transcriptomic analysis of bone biopsies; (2) delineate the role of bone-derived hormones on fat gain with ART initiation, (3) evaluate associations between DNA methylation signatures and osteoporosis in women with HIV. Each Aim is designed specifically to augment the training of junior investigators. The K24 provides me opportunity for formal training in high dimensional data analyses and mentored experiential training with the proposed epigenome analyses. A central component of my mentoring program is an individualized approach to training, which includes a needs assessment of core research competencies and an ongoing evaluation process. I will draw upon the superb resources and multidisciplinary expertise at Columbia University and within HIV research networks that I have worked in throughout my career, especially the MACS/WIHS Combined Cohort Study and the AIDS Clinical Trials Group. In addition, a Mentor Advisory Committee consisting of experienced leaders in POR and education at Columbia University will guide me in building a structured and sustainable mentoring program to develop the next generation POR investigators in HIV research.