Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4 + T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4 + T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4 + T cells when compared with naive, central, and transitional memory CD4 + T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.

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HIV persists in cells despite antiretroviral therapy, however the influence of cellular mechanisms such as activation, differentiation and proliferation upon the distribution of proviruses over time is unclear. To address this, we used full-length sequencing to examine proviruses within memory CD4+ T-cell subsets longitudinally in eight participants. Over time, the odds of identifying a provirus increased in effector and decreased in transitional memory cells. In all subsets, the more activated (HLA-DR-expressing) cells contained a higher frequency of intact provirus, as did more differentiated cells such as the transitional and effector memory subsets. The proportion of genetically-identical proviruses increased over time, indicating that cellular proliferation was maintaining the persistent reservoir, however, the number of genetically-identical proviral clusters in each subset was stable. As such, key biological processes of activation, differentiation and proliferation influence the dynamics of the HIV reservoir and must be considered during the development of any immune intervention.

Importance COVID-19 mRNA vaccine-associated myocarditis has previously been described; however specific features in the adolescent population are currently not well understood. Objective To describe myocarditis adverse events following immunisation reported following any COVID-19 mRNA vaccines in the adolescent population in Victoria, Australia. Design Statewide, population-based study. Setting Surveillance of Adverse Events Following Vaccination in the Community (SAEFVIC) is the vaccine-safety service for Victoria, Australia. Participants All SAEFVIC reports of myocarditis and myopericarditis in 12–17-year-old COVID-19 mRNA vaccinees submitted between 22 February 2021 and 22 February 2022, as well as accompanying diagnostic investigation results where available, were assessed using Brighton Collaboration criteria for diagnostic certainty. Exposures Any mRNA COVID-19 vaccine. Main outcomes/Mmeasure Confirmed myocarditis as per Brighton Collaboration criteria (levels 1–3). Results Clinical review demonstrated definitive (Brighton level 1) or probable (level 2) diagnoses in 75 cases. Confirmed myocarditis reporting rates were 8.3 per 100 000 doses in this age group. Cases were predominantly male (n=62, 82.7%) and post dose 2 (n=61, 81.3%). Rates peaked in the 16–17-year-old age group and were higher in males than females (17.7 vs 3.9 per 100 000, p=<0.001). The most common presenting symptoms were chest pain, dyspnoea and palpitations. A large majority of cases who had a cardiac MRI had abnormalities (n=33, 91.7%). Females were more likely to have ongoing clinical symptoms at 1-month follow-up (p=0.02). Conclusion Accurate evaluation and confirmation of episodes of COVID-19 mRNA vaccine-associated myocarditis enabled understanding of clinical phenotypes in the adolescent age group. Any potential vaccination and safety surveillance policies needs to consider age and gender differences.

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and (2) the predicted probability of good outcome according to core volume and mismatch ratio in the MT group (Figure 3 from Reference 1), showing that increasing core volume significantly mitigates the relationship between mismatch ratio and clinical effects of MT versus BMM.Regarding safety, the aim of our study was not to determine the factors associated with parenchymal hemorrhage (PH) after MT, but whether the persistence of significant penumbra modifies the effects of MT in comparison to BMM on PH. Our findings show a higher risk of PH in the MT group, regardless of the mismatch ratio. In other words, the major benefits derived from penumbral salvage following MT in patients with significant mismatch clearly outweighed any negative impact of PH on functional outcome. Conversely, the lack of beneficial effect of MT on outcome together with the higher odds of PH points to MT being not only "not beneficial," but also potentially harmful in patients without mismatch.Finally, it was not possible to "factor in the model" the imaging-to-puncture delay, as per definition the BMM group had no groin puncture. However, the imaging-to-puncture delay in the MT group did not differ according to the occurrence of PH: 51 minutes (interquartile range [IQR] = 44-74) versus 63 minutes (IQR = 45-78) in patients with versus without PH, respectively (p = 0.88).

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Focus of Presentation ‘Cluster Tracker’ is an automated tool for spatial cluster detection of notifiable disease data collected by the Department of Health (DH), Victoria. The tool combines R statistical software and a SaTScan cluster detection algorithm (prospective space-time permutation scan statistic) to detect notifiable disease case clusters in Victoria and is presently implemented for salmonellosis (categorised by type and/or MLVA). The objective of the tool is to conduct an initial screening of case data to improve the prioritisation of salmonellosis cases for epidemiological investigation. Findings The Cluster Tracker tool parameters have been validated using historical data from 2017-2018, comparing DH outbreak and cluster investigations identified by usual surveillance activities with clusters detected by the Cluster Tracker tool. Parameter selection considered cluster detection agreement and disagreement, disease-specific epidemiological characteristics, and operational requirements. The Cluster Tracker tool was able to provide closely-aligned agreement with existing DH outbreak and cluster investigations using the validated parameters. Implications This automated spatial cluster detection tool complements existing desktop surveillance of salmonellosis notifications to enhance public health decision making, and serves as an example of how spatial methods can improve real-time surveillance. Key messages Advanced spatial statistical tools have a role alongside traditional methods to make better use of limited epidemiological capacity and improve the timeliness and prioritisation of surveillance activities for notifiable diseases.