Statutory health insurance-covered pre-exposure prophylaxis in Germany: changing trends in nationwide tenofovir disoproxil/emtricitabine prescriptions during the COVID-19 pandemic

Background: In 2019, Germany introduced a law to reimburse high-incidence populations for pre-exposure prophylaxis (PrEP), prescribed as tenofovir-disoproxil/emtricitabine (TDF/FTC), via statutory health insurance (SHI). We studied changes in TDF/FTC-prescriptions after the implementation of this law and during the COVID-19 pandemic.Methods: We performed an interrupted time series analysis with monthly prescriptions per defined time period as the outcome. We considered the introduction of SHI-covered PrEP (09/2019) as an interruption, and four COVID-19 waves and two national lockdowns (2020–2021) as explanatory variables. We extrapolated prescriptions had the lockdowns not occurred, and compared this to the actual prescriptions. We performed sub-analyses based on stratification by five federal states with the highest proportion of PrEP users. We assessed the models’ goodness-of-fit based on the adjusted R-squared using RStudio.Results: The best fitting model included SHI-covered PrEP and the first COVID-19 lockdown (04/2020). The decrease in prescriptions during the first lockdown was significant nationally, and in the five federal states for single-month prescriptions. The first lockdown resulted in reductions of 57.7% (95% prediction interval (PI): 23.0%–92.4%) for single-month prescriptions, while 17.4% (95% PI: 0.28%–34.5%) nationally, and 13.9% (95% PI: -3.67%–31.5%) for 3-month prescriptions.Conclusion: Introduction of SHI-covered PrEP resulted in a doubling of TDF/FTC-prescriptions nationwide in the first month alone. A drop in prescriptions was most apparent after the first lockdown, and particularly affected PrEP initiations, possibly due to reduced healthcare access and behavioural changes. Ongoing monitoring of TDF/FTC-prescriptions is needed to safeguard access to preventative care such as PrEP and particularly PrEP initiation during public health crises like COVID-19

Outbreak of imported diphtheria with Corynebacterium diphtheriae among migrants arriving in Germany, 2022

From July 2022, cases of imported diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany. Up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory- confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n = 17). Phylogeny and available journey information indicate that most cases (n = 19) were infected along the Balkan route. Active case finding, increased laboratory preparedness and epicentre localisation in countries along this route are important.Peer Reviewe

The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy

Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.</p

Closing the gap to cure:: Clinical strategies targeting the HIV reservoir

Closing the gap to cure: Clinical strategies targeting the HIV reservoir The introduction of antiretroviral treatment (ART) has dramatically improved the life expectancy of people living with HIV (PLWH). However, since the start of the epidemic in the early 1980s, 33 million people have lost their life due to aids-related illness. This high mortality underlines the importance of awareness of HIV, its diagnosis and treatment, and also its cure. The main barrier to finding a cure for HIV is the so-called HIV reservoir: long-lived human immune cells with HIV integrated in their DNA form this latent reservoir. Therefore, strategies to cure HIV focus on reducing the HIV reservoir. For example, this can be done by starting ART as early as possible during an acute HIV infection, or through reactivation of the latent HIV reservoir which allows detection and subsequent elimination by the immune system. In her thesis, Henrieke Prins introduces novel clinical treatment strategies aimed at curing HIV. She describes promising patient cohorts and clinical studies that help us realize this goal. These studies are a joint effort by the multidisciplinary research group called ‘Erasmus MC HIV Eradication Group’ (EHEG) that focuses on HIV cure-focused translational research. The studies described in her thesis form the basis for encouraging future clinical strategies to bring us one step closer to viral suppression in the absence of ART, in other words, clinical HIV cure

Cohort profile: The Netherlands Cohort Study on Acute HIV infection (NOVA), a prospective cohort study of people with acute or early HIV infection who immediately initiate HIV treatment

Purpose Initiation of combination antiretroviral therapy (cART) during acute or early HIV-infection (AEHI) limits the size of the viral reservoir and preserves immune function. This renders individuals who started cART during AEHI promising participants in HIV-cure trials. Therefore, we established a multicentre prospective cohort study in the Netherlands that enrols people with AEHI. In anticipation of future cure trials, we will longitudinally investigate the properties of the viral reservoir size and HIV-specific immune responses among cohort participants. Participants Participants immediately initiate intensified cART: dolutegravir, emtricitabine/tenofovir and darunavir/ritonavir (DRV/r). After 4 weeks, once baseline resistance data are available, DRV/r is discontinued. Three study groups are assembled based on the preparedness of individuals to participate in the extensiveness of sampling. Participants accepting immediate treatment and follow-up but declining additional sampling are included in study group 1 ( € standard') and routine diagnostic procedures are performed. Participants willing to undergo blood, leukapheresis and semen sampling are included in study group 2 ( € less invasive'). In study group 3 ( € extended'), additional tissue (gut-associated lymphoid tissue, peripheral lymph node) and cerebrospinal fluid sampling are performed. Findings to date Between 2015 and 2020, 140 individuals with AEHI have been enrolled at nine study sites. At enrolment, median age was 36 (IQR 28-47) years, and 134 (95.7%) participants were men. Distribution of Fiebig stages was as follows: Fiebig I, 3 (2.1%); II, 20 (14.3%); III, 7 (5.0%); IV, 49 (35.0%); V, 39 (27.9%); VI, 22 (15.7%). Median plasma HIV RNA was 5.9 (IQR 4.7-6.7) log10 copies/mL and CD4 count 510 (IQR 370-700) cells/mm 3. Median time from cART initiation to viral suppression was 8.0 (IQR 4.0-16.0) weeks. Future plans The Netherlands Cohort Study on Acute HIV infection remains open for participant enrolment and for additional sites to join the network. This cohort provides a unique nationwide platform for conducting future in-depth virological, immunological, host genetic and interventional studies investigating HIV-cure strategies

HIV transmission among acutely infected participants of a Dutch cohort study 2015-2021 is not associated with large, clustered outbreaks

OBJECTIVE: Timely identification of acute or early HIV infection (AEHI) is important to help prevent onward transmission, and understanding the number of secondary infections resulting from individuals with AEHI is key to planning HIV prevention services and case finding. DESIGN: We performed a phylogenetic investigation of a dense sample of individuals with AEHI who took part in the Netherlands Cohort Study on Acute HIV infection (NOVA) in the Netherlands during 2015-2021. METHODS: Transmission clusters were identified using phylogenetic analyses based on HIV pol sequences. The Tamura-Nei model was used to estimate genetic distance. A number of 1000 bootstraps was used to check the reliability of clustering using maximum likelihood. A cluster was defined as having a bootstrap value of at least 95% and a genetic distance of at most 1.5%. Sensitivity analyses using different values for the bootstrap and genetic distance were performed to study the reproducibility of the clustering. RESULTS: Of the 156 participants included in NOVA between July 2015 and April 2021, 134 individuals for whom baseline characteristics and genotypic resistance data at baseline were available could be included. We identified 10 clusters, but the majority of persons (111/134) were not part of a cluster, suggesting mainly independent transmission events. CONCLUSION: Mainly independent transmission events among a study population consisting predominantly of MSM in a low-incidence high-resource setting is likely the result of active AEHI case finding and direct start of treatment, and the roll-out over recent years of preventive measures such as preexposure prophylaxis