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INTRODUCTION: In France, oral pre-exposure prophylaxis (PrEP) for HIV prevention has been publicly available since 2016, mainly targeting at men who have sex with men (MSM). Reliable and robust estimations of the actual PrEP uptake among MSM on a localized level can provide additional insights to identify and better reach marginalized MSM within current HIV prevention service provision. This study used national pharmaco-epidemiology surveillance data and regional MSM population estimations to model the spatio-temporal distribution of PrEP uptake among MSM in France 2016-2021 to identify marginalized MSM at risk for HIV and increase their PrEP uptake. METHODS: We first applied Bayesian spatial analyses with survey-surveillance-based HIV incidence data as a spatial proxy to estimate the size of (1) regional HIV-negative MSM populations and (2) MSM who could be eligible for PrEP use according to French PrEP guidelines. We then applied Bayesian spatio-temporal ecological regression modelling to estimate the regional prevalence and relative probability of the overall- and new-PrEP uptake from 2016 to 2021 across France. RESULTS: HIV-negative and PrEP-eligible MSM populations vary regionally across France. Île-de-France was estimated to have the highest MSM density compared to other French regions. According to the final spatio-temporal model, the relative probability of overall PrEP uptake was heterogeneous across France but remained stable over time. Urban areas have higher-than-average probabilities of PrEP uptake. The prevalence of PrEP use increased steadily (ranging from 8.8% [95% credible interval 8.5%;9.0%] in Nouvelle-Aquitaine to 38.2% [36.5%;39.9%] in Centre-Val-de-Loire in 2021). CONCLUSIONS: Our results show that using Bayesian spatial analysis as a novel methodology to estimate the localized HIV-negative MSM population is feasible and applicable. Spatio-temporal models showed that despite the increasing prevalence of PrEP use in all regions, geographical disparities and inequalities of PrEP uptake continued to exist over time. We identified regions that would benefit from greater tailoring and delivery efforts. Based on our findings, public health policies and HIV prevention strategies could be adjusted to better combat HIV infections and to accelerate ending the HIV epidemic.

A major pharmacological strategy toward HIV cure aims to reverse latency in infected cells as a first step leading to their elimination. While the unbiased identification of molecular targets physically associated with the latent HIV-1 provirus would be highly valuable to unravel the molecular determinants of HIV-1 transcriptional repression and latency reversal, due to technical limitations, this has been challenging. Here we use a dCas9 targeted chromatin and histone enrichment strategy coupled to mass spectrometry (Catchet-MS) to probe the differential protein composition of the latent and activated HIV-1 5′LTR. Catchet-MS identified known and novel latent 5′LTR-associated host factors. Among these, IKZF1 is a novel HIV-1 transcriptional repressor, required for Polycomb Repressive Complex 2 recruitment to the LTR. We find the clinically advanced thalidomide analogue iberdomide, and the FDA approved analogues lenalidomide and pomalidomide, to be novel LRAs. We demonstrate that, by targeting IKZF1 for degradation, these compounds reverse HIV-1 latency in CD4+ T-cells isolated from virally suppressed people living with HIV-1 and that they are able to synergize with other known LRAs.

Background: Although key populations (KPs), such as men-who-have-sex-with-men (MSM) are disproportionately affected by HIV, many prevention and treatment services are not easily accessible for KP members. To address the needs of KPs, Thailand established pre-exposure prophylaxis (PrEP) service delivery together with and led by KP members. This study determines the epidemiological impact and cost-effectiveness of key population-led (KP-led) PrEP. Methods: We calibrated a compartmental deterministic HIV transmission model to the HIV epidemic among Thai MSM. Besides KP-led PrEP, we included other Thai service delivery models of PrEP (fee-based PrEP, the government PrEP program).Data on consistent PrEP use (5 years daily use, 95% effectiveness for preventing HIV) came from Thai PrEP delivery models. For the period 2015–2032, we ranged the number of PrEP starters (40,000–120,000), effectiveness of PrEP (45%–95%), and proportion of consistent users (10%–50%). The analysis started in 2015 when PrEP was introduced. A cost-effectiveness ratio of

Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia, and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to characterize associations of serum immunological, hemostatic or kidney injury markers to disease severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic patients (9 platelets/L) compared to patients with higher platelet counts, RANTES was significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below 30 m/min/1.73 m2. The increased expression of these markers specifically indicates pathology in glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this cytokine in the pathogenesis of kidney dysfunction.

Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered. We have established a European collaboration, HepCare, to perform in-depth analysis regarding RAS prevalence, patterns, and multiclass occurrence. Methods: Data were extracted from the HepCare cohort of patients who previously failed DAA therapy. Geno—and subtypes were provided by submitters and mostly based on in-house assays. They were reassessed using the Comet HCV subtyping tool. We considered RAS to be relevant if they were associated with DAA failure in vivo previously reported in literature. Results: We analyzed 938 patients who failed DAA therapy from ten different European countries. There were 239 genotypes (GT) 1a, 380 GT1b, 19 GT2c, 205 GT3a, 14 GT4a, and 68 GT4d infections. Several unusual subtypes (n = 15) (GT1b/g/l, GT3b, GT4k/n/r/t) were present. RAS appeared in over 80% of failures and over a quarter had three or more RAS. Multiclass RAS varied over target region and genotype between 0–48%. RAS patterns such as the Q30R + L31M and Q30R + Y93H in GT1a, the L31V + Y93H and L31V + Y93H for GT1b, and A30K + L31M and A30K/V + Y93H for GT3a all occurred with a prevalence below 5%. Conclusion: RAS occur frequently after DAA failures and follow a specific genotype and drug related pattern. Interpretation of the influence of RAS on retreatment is challenging due to various patterns, patients’ characteristics, and previous treatment history. Moving towards HCV elimination, an ongoing resistance surveillance is essential to track the presence of RAS, RAS patterns and gather data for a re-treatment algorithm.

A substantial number of studies have been performed across the world to determine transmitted drug resistance. Large variations between different parts of the world can be expected because of differences in availability over time of treatment. Time trend analyses are often not possible because of small numbers of included patients. In this review, we present the available data on the transmission of drug-resistant HIV, with a major emphasis on the time trends of drug resistance prevalences. We identified relevant literature by searching in PubMed through September 2009. Studies were grouped, according to the year of data collection, into the following time periods: < 2001, 2001-2003, > 2003. We selected a total of 215 studies, which included 43,170 patients. The following prevalences of transmission of drug-resistant HIV were found, in rank order: North America (12.9%), Europe (10.9%), Latin America (6.3%), Africa (4.7%), and Asia (4.2%). Changes over time in particular drugs classes were found in all parts of the world. Nucleoside reverse transcriptase inhibitor resistance declined over time in North America (p = 0.03), Europe (p < 0.001), and Latin America (p < 0.001). The decline in nucleoside reverse transcriptase inhibitor resistance reflects the improvement of treatment regimens in resource-rich settings. In contrast the resistance prevalence increased in Asia (p = 0.047) and Africa (p < 0.001). This can be explained by the antiretrovirals becoming more available during recent years in these continents. Nonnucleoside reverse transcriptase inhibitor resistance rose over time in North America (p < 0.001), Europe (p < 0.001), Latin America (p < 0.001), and Asia (p = 0.01). This paper gives a complete overview of the epidemiology of resistance of antiretroviral drugs in drug-naive patients worldwide. The time trends that were observed seem to reflect changes in describing prescriptions over time. Changes include the more wide-spread use of antiretroviral drugs in developing countries and the development of therapies from low-active mono-therapies to highly active antiretroviral regimens in the industrialized countries. (AIDS Rev. 2012;14:17-27)

Background SARS-CoV-2 RT-PCR assays are more sensitive than rapid antigen detection assays (RDT) and can detect viral RNA even after an individual is no longer infectious. RDT can reduce the time to test and the results might better correlate with infectiousness. Aim We assessed the ability of five RDT to identify infectious COVID-19 cases and systematically recorded the turnaround time of RT-PCR testing. Methods Sensitivity of RDT was determined using a serially diluted SARS-CoV-2 stock with known viral RNA concentration. The probability of detecting infectious virus at a given viral load was calculated using logistic regression of viral RNA concentration and matched culture results of 78 specimens from randomly selected non-hospitalised cases. The probability of each RDT to detect infectious cases was calculated as the sum of the projected probabilities for viral isolation success for every viral RNA load found at the time of diagnosis in 1,739 confirmed non-hospitalised COVID-19 cases. Results The distribution of quantification cycle values and estimated RNA loads for patients reporting to drive-through testing was skewed to high RNA loads. With the most sensitive RDT (Abbott and SD Biosensor), 97.30% (range: 88.65–99.77) of infectious individuals would be detected. This decreased to 92.73% (range: 60.30–99.77) for Coris BioConcept and GenBody, and 75.53% (range: 17.55–99.77) for RapiGEN. Only 32.9% of RT-PCR results were available on the same day as specimen collection. Conclusion The most sensitive RDT detected infectious COVID-19 cases with high sensitivity and may considerably improve containment through more rapid isolation and contact tracing.