Real Time Phylogeny and Contact Tracing to Disrupt HIV Transmission Kantor, Rami MD SUMMARY Prevention of HIV transmission is still a major global challenge, and innovative methods are needed for its disruption. Though actual transmission networks are unknown, characterizing social and phylogenetic networks can guide prevention interventions. Contact tracing is the current public health tool to derive social networks and identify, notify, test and link to care partners of newly-diagnosed HIV cases. Phylogenetic analysis of available sequences is used in research to characterize epidemics and has facilitated outbreak investigations. However, real time integration of phylogenetics with contact tracing on a public health, state- wide level has not been evaluated. We propose to prospectively integrate phylogenetic analysis with contact tracing in real time, and evaluate the impact of such integration on HIV infection in Rhode Island (RI). We hypothesize that real time use of information from phylogenetic inference can enhance contact tracing, improve HIV testing, diagnoses and linkage to care, and disrupt transmission. The Specific Aims are to: (1) Conduct real time phylogenetic analyses of patient-level sequence data; (2) Augment phylogenetic inference by increased sampling and more comprehensive testing; and (3) Evaluate the benefit of real time integration of phylogenetics with contact tracing efforts. We will develop and automate tools to incorporate phylogenetic and phylodynamic inference into contact tracing, explore its enhancement, and evaluate its real time impact, with special consideration of key populations like men who have sex with men, intravenous drug users and persons with HIV drug resistance. We expect that this approach will improve identification and linkage to care of infected-unaware individuals, infected-aware individuals not linked to care, and uninfected individuals that are at high risk of infection. The main premise of this proposal is that phylogenetic networks contain information which can expand social networks and impact HIV transmission. If our hypothesis is correct, this research will have high impact on HIV prevention and the care continuum and disrupt HIV transmission in Rhode Island. The rigor of our research approach is strengthened by our multidisciplinary team of clinicians, public health officials, statisticians, bioinformaticians, evolutionary and molecular biologists, combined with our relevant existing data and expertise, the small size of the state and the strong and close academic-public health partnership. Furthermore, important and essential ethics considerations are directly addressed and incorporated throughout. Such an approach will make results generalizable and sustainable, allowing focused resource allocation and continuous implementation and generalization of findings. In 2013 the Director of the RI Department of Health declared the vision of ?Getting to Zero? new HIV infections in the state within the next five years, however apparent increases in transmission among high risk networks has impeded progress. This proposal will help bring small RI closer to its goal of being the first state to get to zero new infections and demonstrate how focusing efforts can prevent HIV transmission in RI and beyond.