An epidemic in transition: impacts of migration and local networks on HIV sequence diversity and infection transmission in Australia Alison Castley 1, Shailendra Sawleshwarkar 2, Rick Varma 2, Belinda Herring 2, Kiran Thapa 2, Doris Chibo 3, Nam Nguyen 4, Karen Hawke 5,6, Rodney Ratcliff 5,6, Dominic E Dwyer 2, David Nolan 1. The Australian Molecular Epidemiology Network-HIV (AMEN-HIV) 1Department of Clinical Immunology, Royal Perth Hospital, Perth WA 6000, 2Western Sydney Sexual Health Centre and Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR-Pathology West, Westmead Hospital and University of Sydney, Westmead NSW 2145, 3 HIV Characterisation Laboratory, Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, 3000, 4 Division of Immunology, HQS Pathology Queensland Central Laboratory, RBWH Herston, QLD 4029, 5 Clinic 275, Royal Adelaide Hospital, Adelaide, Australia, 6 Department of Microbiology and Infectious Diseases, SA Pathology, Adelaide South Australia. Background HIV diagnosis rates have steadily increased in Australia over the past 13 years 26% increase in population rate since ,253 new cases in 2012 (10% compared to 2011) set against downward global trend in new HIV diagnoses. HIV genotype determination routinely performed in an Australian setting pre-treatment provides valuable information on the geographic origin of the infecting HIV-1 subtype can also identify transmission networks through phylogenetic analysis identifies transmitted drug resistance mutations Collaboration established involving HIV-1 genotyping services in five states (NSW, VIC, SA, QLD & WA)

Methods 4432 HIV positive patients identified during Age and gender and Australian state noted, no other identifiable data. HIV-1 subtype determined using the Stanford Drug Resistance Database. Phylogenetic analysis performed utilising BioEdit Sequence Alignment Editor tool and Molecular Evolutionary Genetics Analysis Version 5 (MEGA V5) to infer phylogenetic clustering patterns based on sequence similarity. Methods previously applied to studies of global HIV-1 transmission networks 1 1 Wertheim JO, et al. The Global Transmission Network of HIV-1. J Infect Dis. 2014;209:304–13 Results (1) Non-B-subtype HIV-1 = 1179 cases (26.6%) increasing overall trend from High proportion of non-B-subtype HIV-1 in West Sydney (average 52%) and WA (45%) throughout Increasing trends in other states, from baseline rates of 10-15% to peak levels of 46% (SA), 36% (VIC) and 23% (Qld).

Methods 4432 HIV positive patients identified during Age and gender and Australian state noted, no other identifiable data. HIV-1 subtype determined using the Stanford Drug Resistance Database. Phylogenetic analysis performed utilising BioEdit Sequence Alignment Editor tool and Molecular Evolutionary Genetics Analysis Version 5 (MEGA V5) to infer phylogenetic clustering patterns based on sequence similarity. Methods previously applied to studies of global HIV-1 transmission networks 1 1 Wertheim JO, et al. The Global Transmission Network of HIV-1. J Infect Dis. 2014;209:304–13 Results (1) Non-B-subtype HIV-1 = 1179 cases (26.6%) increasing overall trend from High proportion of non-B-subtype HIV-1 in West Sydney (average 52%) and WA (45%) throughout Increasing trends in other states, from baseline rates of 10-15% to peak levels of 46% (SA), 36% (VIC) and 23% (Qld). Non-B-subtype in 73% of females (416/570) across all states with no apparent time trend. Steady increasing trend in non- B-subtype among males across all states. Overall rate 19.8% (763/3862).

Results (2) Figure 6. Phylogenetic representation of the changes in HIV-1 diversity seen in Western Australia from (A), (B) and (C), [red=CRF01-AE; blue=C subtype; black= B subtype; aqua=others]. Phylogenetic analyses (WA) demonstrate increasing HIV-1 diversity over time. Non-B-subtype HIV-1 transmission clusters are generally pairs associated with male/female partnerships, with larger clusters within male networks. Subtype-B HIV-1 predominantly male, characterised by larger cluster sizes with evidence of local transmission networks up to 27 individuals.

Results (2) Conclusions Figure 6. Phylogenetic representation of the changes in HIV-1 diversity seen in Western Australia from (A), (B) and (C), [red=CRF01-AE; blue=C subtype; black= B subtype; aqua=others]. Phylogenetic analyses (WA) demonstrate increasing HIV-1 diversity over time. Non-B-subtype HIV-1 transmission clusters are generally pairs associated with male/female partnerships, with larger clusters within male networks. Subtype-B HIV-1 predominantly male, characterised by larger cluster sizes with evidence of local transmission networks up to 27 individuals. First nationwide survey of HIV molecular epidemiology in Australia reveals increasing subtype diversity with the emergence of non-B-subtypes among females and males Consistent with changing patterns of migration, overseas travel and domestic factors over time and between states. Domestic transmission clusters predominantly involve HIV-1 B-subtype strains within male- dominated networks, with emerging evidence of onward transmission of non-B subtype HIV-1 within Australia. This study highlights the complex interplay between travel, migration and domestic factors that contribute towards new HIV-1 infections, changing global epidemiological profiles, and growing viral diversity.