Background HIV diagnosis rates have steadily increased in Australia over the past 13 years

1. An epidemic in transition: impacts of migration and local networks on HIV sequence diversity and infection transmission in Australia 2005-2012 Alison Castley1, Shailendra Sawleshwarkar2, Rick Varma2, Belinda Herring2, Kiran Thapa2, Doris Chibo3, Nam Nguyen4, Karen Hawke5,6, Rodney Ratcliff5,6, Dominic E Dwyer2, David Nolan1. 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 2003 • 1,253 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)

2. Methods • 4432 HIV positive patients identified during 2005-2012. • 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 networks1 1Wertheim 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 2005-2012 • 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).

3. Methods • 4432 HIV positive patients identified during 2005-2012. • 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 networks1 1Wertheim 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 2005-2012 • 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).

4. Results (2) • 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. Figure 6. Phylogenetic representation of the changes in HIV-1 diversity seen in Western Australia from 2000-2004 (A), 2005-2008 (B) and 2009-2012 (C), [red=CRF01-AE; blue=C subtype; black= B subtype; aqua=others]. Figure 6. Phylogenetic representation of the changes in HIV-1 diversity seen in Western Australia from 2000-2004 (A), 2005-2008 (B) and 2009-2012 (C), [red=CRF01-AE; blue=C subtype; black= B subtype; aqua=others].

5. Results (2) • 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. Conclusions • 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. Figure 6. Phylogenetic representation of the changes in HIV-1 diversity seen in Western Australia from 2000-2004 (A), 2005-2008 (B) and 2009-2012 (C), [red=CRF01-AE; blue=C subtype; black= B subtype; aqua=others]. Figure 6. Phylogenetic representation of the changes in HIV-1 diversity seen in Western Australia from 2000-2004 (A), 2005-2008 (B) and 2009-2012 (C), [red=CRF01-AE; blue=C subtype; black= B subtype; aqua=others].