Norbert Bannert

Background: HIV and HCV share similar routes of infection. Individuals carrying both viruses experience a faster progression of the liver disease. We have analyzed people with new HIV-1 diagnoses in Germany for active or resolved HCV infection for over ten years. The time period covers the introduction of direct acting antivirals (DAA), a paradigmatic shift in HCV therapy. Methods: A central component of the HIV surveillance in Germany is the notification of new diagnoses. Residual blood samples from 16,539 people with new HIV-1 diagnoses reported between 2009 and 2019 were examined for HCV antigen and/or antibodies. Reactive cases were further investigated for active or resolved HCV infection by RT-qPCR. The results were analyzed with socio-demographic information from the notification forms. Results: The study includes samples from 48.0% of all notified HIV-1 diagnoses. The seroprevalence of cases with HCV antigen, antibodies or both, representing active and resolved infections was 6.2% with stable seroprevalence. The average proportion of resolved infections among those was 33.0% with a significant increase since the introduction of DAAs in 2012 (p _{Trend_2012-2019} = 0.028) reaching 48.2% in 2019. The highest proportion of active and resolved cases (73.7%) was found in people who inject drugs (PWIDs). This transmission group had the lowest percentage of resolved infections with 29.4%. The proportion of active and resolved cases in persons with heterosexual mode of transmission (HET) and in men who have sex with men (MSM) was 3.8% and 2.6%, respectively. The peak percentage of resolved infections was found in MSM (40.0%), followed by HET (36.6%). The proportion of active and resolved cases among individuals with non-German origin was higher than in people with German origin (8.8%, versus 4.3%; p < 0.001) and the proportion of resolved HCV infections lower (27.8% versus 34.0%; p = 0.027). Conclusions: The proportion of resolved HCV infections among people newly diagnosed with HIV-1 increased after the introduction of DAAs in Germany. The high prevalence and the low proportion of resolved HCV infections reveal that unmet diagnostic and therapeutic needs exist among PWIDs. The higher proportion of active and resolved cases among individuals of non-German origin particularly requires greater public health attention.

Objectives: People living with HIV (PLWH) are a risk group for severe symptoms and higher mortality during COVID-19. We analyzed the dynamic rise of SARS-CoV-2 seroprevalence induced by coinfections and vaccinations in PLWH in the first three years of the pandemic in Germany and compared it with corresponding data available for the general population. Methods: Each month on average 93 blood samples from the German HIV-1 Seroconverter Cohort, a prospective longitudinal multicenter study that includes PLWH whose date of seroconversion is well defined, were received. The samples from 1569 PLWH were tested for the presence of anti-S1 and if positive, also for anti-N antibodies. Results: In 2020 the number of anti-S1 positive cases/month was between 0.0 and 6.9% (average 1.6%). Since then the anti-S1 prevalence increased reaching already 35% (33/94) in May 2021. At that time 3.2% of the cases were also anti-N positive. In 2022 the average anti-S1 seroprevalence reached 97.5%. In the vaccination era a positive anti-N response was associated with a younger age and females were overrepresented among anti-S1/anti-N negative samples (assuming no vaccination or infection). Conclusions: The average 1.6% anti-S1 seroprevalence in the cohort in 2020 was comparable to that in the general population (1.3%). The increase in anti-S1 seroprevalence in the first half of 2021 occurred slightly earlier. This increase was likely caused by the prioritization of PLWH at the early stage of the vaccination campaign and by infections during the third wave of the pandemic.

Syncytin-1 and -2 are glycoproteins encoded by human endogenous retrovirus (hERV) that, through their fusogenic properties, are needed for the formation of the placental syncytiotrophoblast. Previous studies suggested that these proteins, in addition to the EnvP(b) envelope protein, are also involved in other cell fusion events. Since galectin-1 is a β-galactoside-binding protein associated with cytotrophoblast fusion during placental development, we previously tested its effect on Syncytin-mediated cell fusion and showed that this protein differently modulates the fusogenic potential of Syncytin-1 and -2. Herein, we were interested in comparing the impact of galectin-1 on hERV envelope proteins in different cellular contexts. Using a syncytium assay, we first demonstrated that galectin-1 increased the fusion of Syncytin-2- and EnvP(b)-expressing cells. We then tested the infectivity of Syncytin-1 and -2 vs. VSV-G-pseudotyped viruses toward Cos-7 and various human cell lines. In the presence of galectin-1, infection of Syncytin-2-pseudotyped viruses augmented for all cell lines. In contrast, the impact of galectin-1 on the infectivity of Syncytin-1-pseudotyped viruses varied, being cell- and dose-dependent. In this study, we report the functional associations between three hERV envelope proteins and galectin-1, which should provide information on the fusogenic activity of these proteins in the placenta and other biological and pathological processes.

Background: The transmission of resistant HIV variants jeopardizes the effective use of antiretrovirals for therapy and prophylaxis. Molecular surveillance of new HIV diagnoses with a focus on prevalence and type of resistance associated mutations and the subtype of circulating viruses is mandatory. Method: From 2017 to 2020, 11,527 new HIV diagnoses were reported in Germany to the Robert Koch Institute (RKI). Protease (PR) and reverse-transcriptase (RT) sequences were obtained from 4559 (39.6%) cases, and PR, RT and integrase (IN) sequences were obtained from 3097 (26.9%) cases. The sequences were analyzed with data from the national HIV reports. Results: Among all cases in the analysis, the proportion of primary resistance was 4.3% for nucleoside reverse-transcriptase inhibitors (NRTIs), 9.2% for non-NRTI (NNRTIs), 3.3% for protease inhibitors (PIs) and 1.4% for integrase inhibitors (INIs). Dual-class resistance was highest for NRTIs/NNRTIs with 1.2%. There was no trend in the proportion of viruses resistant to drug classes. Most individual key mutations associated with relevant resistance had a prevalence below 1% including K65R (0.1%) and M184V (0.6%). A notable exception was K103NS, with a prevalence of 2.9% and a significant increase (p_Trend=0.024) during 2017–2020. In this period, diagnoses of infections with HIV-1 subtype B were the most common at 58.7%, but its prevalence was declining (p_Trend=0.049) while the frequency of minority subtypes (each < 1%) increased (p_Trend=0.007). Subtype B was highest (75.6%) in men who have sex with men (MSM) and lowest in reported heterosexual transmissions (HETs, 22.6%). Conclusion: The percentage of primary resistance was high but at a stable level. A genotypic determination of resistance is therefore still required before the start of therapy. The subtype diversity of circulating HIV-1 is increasing.

HIV infections which are diagnosed at advanced stages are associated with significantly poorer health outcomes. In Germany, the proportion of persons living with HIV who are diagnosed at later stages has remained continuously high. This study examined the impact of regional socioeconomic deprivation on the timing of HIV diagnosis. We used data from the national statutory notification of newly diagnosed HIV infections between 2011 and 2018 with further information on the timing of diagnosis determined by the BED-Capture-ELISA test (BED-CEIA) and diagnosing physicians. Data on regional socioeconomic deprivation were derived from the German Index of Socioeconomic Deprivation (GISD). Outcome measures were a non-recent infection based on the BED-CEIA result or an infection at the stage of AIDS. The effect of socioeconomic deprivation on the timing of diagnosis was analysed using multivariable Poisson regression models with cluster-robust error variance. Overall, 67.5% (n = 10,810) of the persons were diagnosed with a non-recent infection and 15.2% (n = 2746) with AIDS. The proportions were higher among persons with heterosexual contact compared to men who have sex with men (MSM) (76.8% non-recent and 14.9% AIDS vs. 61.7% non-recent and 11.4% AIDS). MSM living in highly deprived regions in the countryside (< 100 k residents) were more likely to have a non-recent infection (aPR: 1.16, 95% CI: 1.05–1.28) as well as AIDS (aPR: 1.41, 95% CI: 1.08–1.85) at the time of diagnosis compared to MSM in less deprived regions in the countryside. No differences were observed among MSM from towns (100 k ≤ 1 million residents) or major cities (≥ 1 million residents), and no differences overall in the heterosexual transmission group. An effect of socioeconomic deprivation on the timing of HIV diagnosis was found only in MSM from countryside regions. We suggest that efforts in promoting HIV awareness and regular HIV testing are increased for heterosexual persons irrespective of socioeconomic background, and for MSM with a focus on those living in deprived regions in the countryside.

A novel tool for the presentation of peptides and small proteins on the surface of human cells has been developed. Our tANCHOR system utilizes tetraspanin anchors containing heterologous amino acid... METHOD SUMMARY We demonstrate that tetraspanins are able to present heterologous antigens instead of their large extracellular loop on the cell surface by employing confocal laser scanning microsco...

Needle and syringe sharing among people who inject drugs (PWID) can result in a rapid regional spread of a human immunodeficiency virus (HIV) variant. Such outbreaks have been identified recently in several countries and have raised public health attention because of an association with new psychoactive substances (NPS). Dried serum spots from approximately 60% of newly diagnosed HIV cases in Germany in 2013–2018 were received together with statutory notification data. Samples were sequenced in the pol-region, genotyped, and viral phylogenies were analyzed. For selected samples, the hepatitis C virus (HCV) status and the presence of NPS were determined. An outbreak of closely related 27 subtype C infections with a core of 11 cases with almost identical sequences was identified using phylogenetic analyses. The first case of the outbreak was diagnosed in 2015, and the last one was in 2018. With exception of 3 infections, all were reported from Munich, the capital of the federal state of Bavaria. Of 26 analyzed outbreak members, 24 (92.3%) had a resolved or viremic HCV coinfection. In 8 of 18 (44%) cases, α-pyrrolidinopentiothiophenone and/or the related substance α-pyrrolidinoheptiophenone was identified. Despite harm reduction services in place, HIV outbreaks of considerable size can occur in PWID. The establishment of a real-time molecular surveillance is advised to rapidly identify outbreaks and target prevention measures.

Shock-and-kill is one of the most advanced, yet unrealized, concepts towards establishment of HIV-1 cure. Treatment with latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACis) exerting chromatin remodelling and gene expression reprogramming, combined with anti-retroviral therapy reactivates HIV-1 transcription in vitro , ex vivo and in vivo . However, HDACi treatment fails to significantly reduce the size of the viral reservoir in people living with HIV-1 (PLHIV). Here, by combining scRNA-seq and functional approaches, we characterised the HDACi treatment-imposed remodulation of CD4+ T-cells’ state and its consequences for HIV-1 latency reversal and the apparent resistance of HIV-1-reactivating cells to immune-mediated elimination. Exposure of CD4 ⁺ T-cells from three aviremic PLHIV with clinically applicable concentrations of Panobinostat markedly reduced the expression of genes mediating T-cell activation and IFN-driven antiviral immunity in a largely CD4 ⁺ T-cell subset-nonspecific manner, with exception of an PLHIV-specific exhausted CD4 ⁺ T-cell subpopulation. Altered transcriptomic profiles were accompanied by large refractoriness to peptide and IL-2/PHA stimulation, and to exogenous type I interferon, that would otherwise induce T-cell activation and expression of a plethora of antiviral genes, respectively. Type I interferon, when added to Panobinostat during HIV-1 reactivation, was unable to counteract HDACi-mediated inhibition of IFN signalling and failed to interfere with HIV-1 reactivation per se . However, it imposed a pre-budding block and boosted surface levels of HIV-1 Env on reactivating cells. Co-treatment with type I IFNs, most prominently IFN-β and -α14, sensitised HIV-1-reactivating cells for killing by NK cells through antibody-dependent cytotoxicity. Together, our study provides proof-of-concept of the benefit of combining a potent LRA with immunostimulatory molecules, such as type I IFNs, to reduce the resistance of HIV-1-reactivating T-cells to immune-mediated elimination to improve current shock-and-kill strategies.