Date Published: May 10, 2017
Publisher: Public Library of Science
Author(s): Alison Castley, Shailendra Sawleshwarkar, Rick Varma, Belinda Herring, Kiran Thapa, Dominic Dwyer, Doris Chibo, Nam Nguyen, Karen Hawke, Rodney Ratcliff, Roger Garsia, Anthony Kelleher, David Nolan, Chiyu Zhang.
Rates of new HIV-1 diagnoses are increasing in Australia, with evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing impact of migration and travel. The present study aims to define HIV-1 subtype diversity patterns and investigate possible HIV-1 transmission networks within Australia.
The Australian Molecular Epidemiology Network (AMEN) HIV collaborating sites in Western Australia, South Australia, Victoria, Queensland and western Sydney (New South Wales), provided baseline HIV-1 partial pol sequence, age and gender information for 4,873 patients who had genotypes performed during 2005–2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a stringent classification of transmission pairs or clusters (bootstrap ≥98%, genetic distance ≤1.5% from at least one other sequence in the cluster).
HIV-1 subtype B represented 74.5% of the 4,873 sequences (WA 59%, SA 68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of sequences, p = 0.3). Significantly more subtype B clusters were comprised of ≥3 sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and significantly more subtype B pairs and clusters were male-only (88% compared to 53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a cluster of any size included; being sequenced in a more recent time period (p<0.001), being younger (p<0.001), being male (p = 0.023) and having a B subtype (p = 0.02). Being in a larger cluster (>3) was associated with being sequenced in a more recent time period (p = 0.05) and being male (p = 0.008).
This nationwide HIV-1 study of 4,873 patient sequences highlights the increased diversity of HIV-1 subtypes within the Australian epidemic, as well as differences in transmission networks associated with these HIV-1 subtypes. These findings provide epidemiological insights not readily available using standard surveillance methods and can inform the development of effective public health strategies in the current paradigm of HIV prevention in Australia.
HIV-1 is highly genetically variable with a continual rapid mutation and recombination associated with an error-prone and non-proofreading reverse transcriptase activity . There are four distinct HIV-1 groups (M, N, O and P) of which the M group accounts for 90% of infections worldwide. Within the M group there are nine phylogenetically distinct subtypes (A-D, F-H, J and K) along with an increasing number of inter-subtype circulating recombinant forms (CRFs). The main HIV-1 subtypes have distinct geographical associations that can provide useful epidemiological information , although there is growing evidence of increasing subtype and inter-subtype HIV-1 genetic diversity in regions previously characterised by specific HIV-1 subtypes [3–6]. Globally, subtype C is the most prevalent and is strongly associated with sub-Saharan African and Indian populations, followed by subtype A (east Africa) and subtype B (western Europe, United States and Australia); these jointly account for 70% of HIV infections [2,7]. Other major subtypes (F, H, J and K) have remained stable at low levels, accounting for around 1% of infections worldwide, whilst subtype D has decreased over time . HIV-1 CRFs account for around 17% of infections worldwide; a 50% increase in the number of total global HIV-1 infections between 2000 and 2007. Unique recombinant forms (URFs) account for approximately 4% of all HIV infections globally, though this proportion can increase to as high as 30% of all new infections in regions where multiple subtypes and CRFs co-circulate, known as recombinant hotspots [8,9].
The outcomes of this study highlight an Australian HIV-1 epidemic characterised by an increasing prevalence of non-B infections with an overall expanding subtype diversity. Just over one quarter of all infections were identified as non-B subtypes, which is slightly lower than observed in recent studies undertaken in North America , Europe  and Belgium . The dominant non-B subtypes identified in Australia are subtype C and CRF01_AE, the main HIV-1 strains circulating amongst sub-Saharan African and south-east Asian populations. A recent report has documented that the increase in CRF01_AE infections into previously low prevalence countries can be attributed to travel from Asian countries [35,36], with Thailand, Malaysia, China and India recently identified in the top 10 countries where an increase in Australian visitors has been recorded . Phylogenetic analysis found that these non-B infections are more likely to occur within heterosexual transmission networks. The similar proportion of males and females infected with subtype C in Australia is consistent with the distribution of heterosexual transmissions documented in sub-Saharan Africa  while the increasing proportion of CRF01_AE infections in Australia amongst both females and males corresponds with south-east Asian patterns of heterosexual transmission and injecting drug use (IDU), as well as increasing MSM transmissions and injecting drug use (IDU) present in south-east Asia [35,47].