PHYLOGENETIC AND NETWORK APPROACHES TO UNDERSTANDING HIV AND HEPATITIS C TRANSMISSION DYNAMICS AMONG KEY POPULATIONS IN INDIA

Injection drug use is increasingly accounting for new HIV and hepatitis C virus (HCV) infections in low- and middle-income countries (LMICs); however, much of what is known about transmission among people who inject drugs (PWID) comes from high-income settings. Additionally, very little is known about real-world injection networks that include indirect ties, particularly from an LMIC. We used viral sequences, individual-level data, and comprehensive social and spatial network data to examine key questions related to HIV/HCV transmission among PWID in India. Our aims were to (1) evaluate methodologies for inferring molecular transmission clusters, (2) examine evidence for sexual transmission of HCV, (3) analyze HCV phylodynamics and factors associated with clustering, and (4) utilize sociometric network data to investigate the role space and network ties. In analyzing genetic and epidemiologic data from 4,994 men who have sex with men in India, we failed to find strong evidence of sexual HCV transmission, with infections appearing to be driven largely by injection drug use. We then used phylogeographic analyses to infer HCV transmission hotspots and geospatial diffusion of virus among PWID populations across four Indian cities. We supplemented these analyses with HIV sequences to draw comparisons within the same population, and in the case of co-infections, evaluate molecular evidence for shared transmission pathways. We found that genetically linked participants with HCV were significantly younger and more likely to live and inject close to one another. Phylogenetic evidence suggested recent and ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses traced HCV spread back to Northeastern India and showed diffusion patterns consistent with drug trafficking routes. Finally, we collected social and spatial network data from 2,512 PWID in New Delhi to examine the role of network-level factors on HIV/HCV transmission. We found that the odds of prevalent HIV and HCV decreased with each additional degree of separation from an infected person and increased among those who injected at a specific location, factors that were independent of individual-level predictors. Together, these findings paint a more complete picture of HIV/HCV transmission among PWID in India and may better inform public health programs