Characterising HIV-1 transmission in Victoria, Australia: a molecular epidemiological study.

Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (R e ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low R e values. Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. Funding: National Health and Medical Research Council, Australian Research Council.

Multicenter clinical comparative evaluation of Alinity m HIV-1 assay performance.

BACKGROUND: Accurate, rapid detection of HIV-1 RNA is critical for early diagnosis, treatment decision making, and long-term management of HIV-1 infection. OBJECTIVE: We evaluated the diagnostic performance of the Alinity m HIV-1 assay, which uses a dual target/dual probe design against highly conserved target regions of the HIV-1 genome and is run on the fully automated Alinity m platform. STUDY DESIGN: This was an international, multisite study that compared the diagnostic performance of the Alinity m HIV-1 assay to four commercially available HIV-1 assays routinely used in nine independent clinical laboratories. Alinity m HIV-1 assay precision, detectability, and reproducibility was compared across four study sites. RESULTS: The Alinity m HIV-1 assay produced comparable results to currently available HIV-1 assays (correlation coefficient >0.995), with an overall bias of -0.1 to 0.10 Log10 copies/mL. The Alinity m HIV-1 assay and its predecessor m2000 HIV-1 assay demonstrated comparable detection of 16 different HIV-1 subtypes (R2 = 0.956). A high level of agreement (>88 %) between all HIV-1 assays was seen near clinical decision points of 1.7 Log10 copies/mL (50 copies/mL) and 2.0 Log10 copies/mL (200 copies/mL). Alinity m HIV-1 assay precision was 0.08 and 0.21 Log10 copies/mL at VLs of 1000 and 50 copies/mL, respectively, with a high level of detectability (≥97 % hit rate) and reproducibility across sites. CONCLUSIONS: The Alinity m HIV-1 assay provides comparable diagnostic accuracy to current HIV-1 assays, and when run on the Alinity m system, has the capacity to shorten the time between diagnosis and treatment.

Analysis of transmitted HIV drug resistance from 2005 to 2015 in Victoria, Australia: a comparison of the old and the new.

Background Baseline genotyping is part of standard-of-care treatment. It reveals that transmitted drug resistance (TDR) continues to be important for the management of HIV infection. Attention is typically focused on determining whether resistance to the protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) occurs. However, the increasing use of integrase inhibitors (INIs) raises a concern that TDR to this class of antiretroviral drug may also occur. METHODS: PI and RTI drug resistance genotyping was performed on blood samples collected between 2005 and 2015 from 772 treatment-naïve Victorian patients infected with HIV within the previous 12 months. Integrase genotyping was performed on 461 of the 485 patient samples collected between 2010 and 2015. RESULTS: In the period 2005-10, 39 of 343 patients (11.4%) had at least one PI- or RTI-associated mutation, compared with 34 of 429 (7.9%) during the period 2011-15. Compared with 2005-10, during 2011-15 there was a significant decline in the prevalence of the non-nucleoside-associated mutation K103N and the nucleoside-associated mutations at codons M41 and T215. One patient was detected with a major INI resistance mutation, namely G118R. However, this mutation is rare and its effect on susceptibility is unclear. A small number of patients (n=12) was infected with HIV containing accessory resistance mutations in the integrase gene. CONCLUSIONS: The lack of transmitted resistance to INIs is consistent with a low level of resistance to this class of drugs in the treated population. However, continued surveillance in the newly infected population is warranted as the use of INIs increases.