HARNESSING HIV AND SYPHILIS NETWORKS TO REDUCE HIV TRANSMISSION IN NORTH CAROLINA Rachael Marie Billock A dissertation submitted to the faculty at the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Epidemiology in the Gillings School of Global Public Health. Chapel Hill 2020 Approved by: Kimberly A. Powers Jennifer L. Lund Peter J. Mucha Brian W. Pence Erika Samoff © 2020 Rachael Marie Billock ALL RIGHTS RESERVED ii ABSTRACT Rachael Marie Billock: Harnessing HIV and Syphilis Networks to Reduce HIV Transmission in North Carolina (Under the direction of Kimberly Powers) Sexual contact networks containing persons diagnosed with HIV and/or syphilis are efficient platforms for delivery of enhanced HIV treatment support to persons living with HIV (PLWH) and prevention resources to HIV-negative persons. We conducted three inter-related studies among men who have sex with men (MSM) in North Carolina (NC) to assess the potential for network-based interventions to reduce HIV transmission. We first generated independent and combined HIV and syphilis networks using contact tracing data for all MSM diagnosed with HIV or syphilis 2015-2017 in NC. We identified network communities, or clusters of densely connected nodes, in the combined network and evaluated interconnectivity between the syphilis and HIV networks by community. Heightened interconnectivity was associated with younger median age; higher proportions of persons self- identifying as Black, non-Hispanic; and higher proportions of syphilis cases diagnosed at sexually transmitted disease clinics. Next, we used NC surveillance data to identify two types of qualifying “network events” among MSM in NC 01/2013-06/2017: being diagnosed with early syphilis or being named as a recent sexual contact of a person diagnosed with HIV or early syphilis. We estimated prevalent and incident viral suppression among previously diagnosed PLWH at and after network events (52.6% and 35.4%, respectively) and assessed the effect of contact tracing services on incident viral suppression. The six-month cumulative incidence of reported viral suppression was 13.1 (95% CI: 8.9, 17.4) percentage points higher after events among persons reached vs. not iii reached by these services. Using linked insurance claims data, we also evaluated prevalent and incident pre-exposure prophylaxis (PrEP) use among HIV-negative network members (5.4% and 4.1%, respectively). Finally, we generated static contact networks with community structure drawn from the combined HIV/syphilis network described above and varied endemic HIV prevalence across network communities. We applied a stochastic transmission model to simulate HIV spread, evaluated community-level HIV incidence rates by endemic community-level HIV prevalence, and modeled the efficiency of community-prevalence-based vs. randomly allocated interventions. PrEP interventions were most efficient when preferentially deployed to susceptible persons in communities with higher endemic HIV prevalences, while viral suppression intervention efficiency did not vary significantly by intervention allocation scheme. iv For the people of North Carolina living with HIV v ACKNOWLEDGMENTS I must first thank Kim Powers, my dissertation advisor, for her endless support during my time at UNC. Kim has generously given so much of her time and has acted as a true mentor over the past five years. She patiently guided my exploration of many potential research questions in the conceptualization of this project, thoughtfully edited countless manuscript drafts, and consistently posed insightful questions and creative solutions. This dissertation would not exist without her kind and knowledgeable direction, or without her personal support at each stage of the process. Prior to beginning this dissertation, I worked as a research assistant with Ann Dennis. Ann introduced me to the field of network analysis, and the skills that I gained under her gentle and expert supervision provided the foundation for these analyses. Ann also supported my development as I learned to work with the surveillance data applied in this dissertation and connected me with collaborators at the NC Division of Public Health (DPH). I am immensely grateful to everyone at NC DPH, particularly the HIV/STD/Hepatitis Surveillance Unit, for sharing their skills, knowledge, and resources. Among many others, Erika Samoff, John Barnhart, Jason Maxwell, and Anna Cope have patiently answered my many questions and modeled constant dedication to the people of North Carolina. Erika has provided an essential voice on my dissertation committee, aiding in the translation of analyses to programmatically meaningful results. She is truly an advocate for people living with HIV, and she inspires me to strive to be the same. Much of the data used in this study were provided by NC DPH. NC DPH does not take responsibility for the scientific validity or accuracy of methodology, results, statistical analyses, or conclusions presented. vi In addition to serving on my committee, Brian Pence is the supervisor of the “Training in Infectious Disease Epidemiology” NIAID grant (5T32AI070114-12) that has funded my dissertation research and supported my professional development over the past two years. In both roles, Brian has offered straightforward solutions to any potential problems, always sharpening my work and fostering my progression as a scientist. Jennifer Lund provided an introduction to pharmacoepidemiology and invaluable guidance in analyses of insurance claims data as a member of my committee. Jenny’s enthusiasm made a new field more approachable and her many insights refined my analyses. Peter Mucha’s work on community detection in networks inspired much of this dissertation, and his personal support in translating his research was instrumental to its success. His service on my committee allowed me to explore new analytical approaches and to envision the application of these methods to public health. I would like to thank Valerie Hudock and Jennifer Moore for their help with the administrative side of this program, for always keeping me on track, and for sharing my excitement at each new stage of the MSPH and PhD. I am also very grateful for the support provided by the Cornoni-Huntley Scholarship in the final year of this degree. I greatly appreciate the support of the staff at the Cecil G. Sheps Center for Health Services Research at UNC, particularly Abigail Haydon, Roger Akers, Joe Meskey, and Eric Eyre. Their patient guidance and willingness to support student work was critical to the success of PrEP-related analyses in Aim 2. Database infrastructure used for this project was supported by the Cecil G. Sheps Center for Health Services Research and the CER Strategic Initiative of UNC’s Clinical and Translational Science Award (UL1TR001111). I would also like to thank Blue Cross Blue Shield of North Carolina for allowing their data to be applied in this dissertation. This work would not have been possible without the contribution of the Disease Intervention Specialists (DIS) who perform contact tracing for persons diagnosed with HIV and syphilis in North Carolina. The often extraordinary efforts of DIS to reach persons diagnosed with HIV and syphilis and their named contacts are the frontline of HIV and syphilis control in vii NC, and meticulous data collection throughout this process enables analyses like those performed here. Most of all, I would like to acknowledge the persons living with HIV, and all others, who are represented in this dissertation. Finally, I would like to thank the many friends that I have made within this program, who helped me believe that I belonged at UNC, and the friends outside of the program who loved, distracted, and uplifted me throughout this process. I want to thank my family, for instilling the joy of science early, and my partner, for his positivity, perspective, and unwavering support. I would not be here without all of you. viii TABLE OF CONTENTS LIST OF TABLES ..................................................................................................................... xiv LIST OF FIGURES ............................................................................................................................. xv LIST OF ABBREVIATIONS ...................................................................................................... xvi CHAPTER ONE: SPECIFIC AIMS .............................................................................................. 1 CHAPTER TWO: BACKGROUND .............................................................................................. 5 A. HIV Epidemiology ......................................................................................................... 5 1. HIV in the Southern United States ........................................................................................ 5 2. HIV in North Carolina ........................................................................................................................................ 7 B. Pre-Exposure Prophylaxis and Antiretroviral Therapy ................................................... 8 1. Pre-Exposure Prophylaxis ...................................................................................... 9 2. Antiretroviral Therapy ............................................................................................ 12 C. HIV/Syphilis Syndemic ...............................................................................................