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Molecular epidemiology of HIV is indispensable for guiding evidence-based interventions, improving health outcomes, and ultimately working towards ending HIV transmission.
New human immunodeficiency virus (HIV) diagnoses in Australia declined by 46% between 2013 and 2022 (here) thanks to sustained community-led responses in combination with public health efforts in implementing prevention measures (here).
Although part of this decline may be due to the restrictions during the coronavirus disease 2019 (COVID-19) lockdowns in 2020 and 2021 leading to restricted movement and change in behaviour, ongoing efforts in increasing HIV testing, early HIV treatment and increased uptake of pre-exposure prophylaxis (PrEP) have been critical in reducing transmission. Highly effective treatments for people with HIV lead to viral suppression, at which point HIV cannot be sexually transmitted (here, here and here), and, when taken as directed, HIV PrEP is nearly 100% effective at preventing acquisition of HIV (here, here and here). These prevention measures have led to a striking decline of HIV infections among gay, bisexual and other men who have sex with men living in the Sydney inner city area (here).
In its final report, the 2023 National HIV Taskforce states that genetic-based surveillance including molecular epidemiology and phylogenetic clustering can be useful in tracking HIV spread, and recommended Australian state and territory governments partner with people living with HIV to develop a pathway for the adoption of molecular epidemiology techniques (here).
Molecular epidemiology and phylogeny are study fields that use genetic data to better understand the patterns of disease transmission. These were highly popularised during the COVID-19 pandemic. Using genome data allows us to investigate what factors drive the HIV epidemic, determine how public health interventions affect transmission, and, importantly, identify gaps in current prevention measures.
Studies involving molecular epidemiology are very cost-effective. For HIV, they make use of data already available via pathology laboratories — HIV genome data are routinely assessed to identify the best treatment strategies for individuals and at the population level for HIV treatment guidelines . The HIV genome is used to check for drug resistance mutations that may affect treatment effectiveness, including PrEP. HIV demographic data (eg, risk exposure) are routinely collected by state public health units for new HIV cases notified, under the auspices of the National Health Security Act 2007 and public health acts of each jurisdiction. These data are used for the quarterly New South Wales HIV Surveillance Reports (here).
Studying the data
Using a combination of HIV genome data and demographic data, we compared similarities and differences in HIV transmission clusters in NSW. Clusters represent a group of genetically similar HIV genomes that are more likely to share a common source (ie, are part of a local transmission network). These networks are drivers of the epidemic and represent gaps in prevention. Cluster analysis is an add-on tool for mapping increased transmission that would not be apparent from data collected with HIV notifications alone (here).
For our research, we used NSW genome data linked to metadata from 2004 to 2018 that include approximately 70% of all new HIV diagnoses in the state. The data are anonymised and results are presented on a population level to preclude the potential identification of individuals.
We first looked at how clustering differs by subtype. The distribution of HIV subtypes is country and region-specific, with Australia, like Europe and the United States, having mainly subtype B infections. Africa is dominated by subtype C infections and South-East Asia by a recombinant form known as circulating recombinant form 01_AE (CRF01_AE; here). In Australia, the latter two non-B subtypes were commonly associated with diagnoses in people born outside of Australia and we wanted to know how these infections compare to local HIV acquisition.
We compared subtype and clustering to region of birth and reported risk exposure, and while non-B subtypes were more likely to be linked to individuals born outside of Australia, these were less commonly found in clusters. This means that infections acquired overseas are not part of local transmission networks and do not contribute to the ongoing epidemic (here). However, we did notice an increase in CRF01_AE diagnoses over time, mainly among individuals reporting male-to-male sex. Also, increased clustering among this group shows us that these infections have been acquired locally and this subtype is now endemic in the state (here).
Next, we looked at subtype B infections that are more commonly found in large clusters (more than ten sequences). To understand how these arise and grow over time, we calculated their growth rate to identify those that may need more urgent public health attention.
Although most clusters grow at a low rate with only one new infection diagnosed every six months, some grow at fast rates with up to three new diagnoses every six months (here). This difference in growth rate may be due to increased transmission but could also be due to differences in contact tracing and efforts in testing. Thus, a fast-growing cluster may not necessarily be reason for concern but may reflect effective contact tracing. We also found clusters that grew very slowly, with long periods of inactivity. These are more concerning as they highlight gaps in prevention such as low testing.
The need for a national database
Our research is not without limitations. First, we do not have data for all new diagnoses and, currently, we only have data for NSW. This limits our understanding overall but specifically affects information on transmission rates across state borders. Second, all our data are retrospective with one to two years’ delay, reducing our ability to rapidly inform public health on the effectiveness of interventions.
Thus, we are working on creating a national HIV database that will allow the timely and national analysis of HIV clusters.
An effective implementation of HIV molecular epidemiology needs to use real-time data such that prevention measures can be timely and targeted to specific changes in the epidemic.
Molecular epidemiology is most effective as an addition to enhance existing public health measures. Such programs have been successfully implemented in North America (here).
Most importantly, however, efforts in designing HIV-specific molecular epidemiology programs for Australia must be done in consultation and collaboration with community representatives and with legal and data privacy advisors (here). Data privacy and security must be ensured as HIV transmission and exposure can still be prosecuted. HIV stigma is omnipresent and its effects inhibit testing, thus perpetuating HIV transmissions.
Molecular epidemiology is indispensable for guiding evidence-based interventions and improve health outcomes. The end goal is ultimately working towards ending HIV transmission.
Dr Francesca Di Giallonardo is a senior research fellow at the Kirby Institute, Faculty of Medicine, UNSW Sydney, and a trained virologist and expert in molecular biology with major research interests in evolutionary biology, disease emergence and genomics.
Dr Phillip Keen is a senior research fellow at the Kirby Institute, Faculty of Medicine, UNSW Sydney, with major research interests in HIV testing and monitoring and evaluation of HIV prevention programs.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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The number of new HIV infections in Australia is now declining impressively. This is in stark contrast to the situation in the early 1980s when eastern Sydney was the national HIV epicentre, especially among the three major groups at highest risk ( men-who-had-sex-with-men, people who sold/bought sex, people who injected drugs), effective prevention was being worked out on the run and no effective treatment was known. HIV prevalence in these three groups is expected soon to be less than 5%. This is a colossal public health achievement. Much is owed to the splendid ten Guiding Principles described on pp 8-9 of the latest National HIV Strategy. No wonder the Strategy has been so successful given the strong commitment to these important principles.
However, the contrast could not be more stark with Australia’s tobacco and vaping policy where these same ten guiding principles should be followed but are completely ignored. No wonder Australia now has a slower decline in its smoking rate than countries like New Zealand or the United Kingdom which have regulated vaping proportionate to risk. The cost of Australia’s failed tobacco and vaping policy is not just the many smoking related deaths and diseases which could be prevented but aren’t, but also the social and economic costs which could be prevented but aren’t and the violence associated with the booming vaping black market.
A great news story.