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The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes’ transforming growth factor-β production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction.

The ongoing COVID-19 pandemic has been impeding HIV diagnosis and treatment worldwide. Data on the impact of COVID-19 on late diagnosis (LD) in Germany are lacking. Here we present novel data of a single-centre German HIV cohort assessing LD during COVID-19.This is a non-interventional, single-centre retrospective cohort assessing the rate of LD comparing HIV diagnoses pre-COVID-19 with those during the COVID-19 pandemic. New diagnoses between 1 January 2019 and 1 February 2020 were classified as pre-COVID-19, and diagnoses between 1 February 2020 and 1 October 2021 were classified as during COVID-19.Between 1 January 2019 and 1 October 2021, 75 patients presented with newly diagnosed HIV infection, 34 pre-COVID-19 and 41 during COVID-19. LD increased to 83% (n = 34/41) during COVID-19 versus 59% (n = 20/34) pre-COVID-19, and CDC stage C3 rose to 44% (n = 18) versus 27%. Hospitalization rate increased to 49% (n = 20) during COVID-19 versus 29% pre-COVID-19, and 12% (n = 5) presented with HIV-associated neurological disease, whereas none were observed in the pre-COVID-19 group. The incidence of LD (p = 0.020), CD4 count 350 cells/μL (p = 0.037) and 200 cells/μL (p = 0.022) were statistically significantly associated with the ongoing COVID-pandemic. An association with HIV transmission risk was borderline significant (p = 0.055).Despite comparable annual rates of new HIV diagnoses, LD has been increasing during the COVID-19 pandemic, resulting in more opportunistic infections and higher hospitalization rates, possibly reflecting pandemic-related shortages in HIV testing and care facilities. Maintaining HIV testing opportunities and access to treatment during a pandemic is crucial so as not to impede WHO elimination goals and so as to prevent an increase in AIDS-related morbidity and mortality.

Zusammenfassung Einleitung Ende 2019 lebten weltweit 38 Millionen Menschen mit HIV, mehr als die Hälfte Mädchen und Frauen. Kenntnis über den HIV-Status der Schwangeren kann eine HIV-Transmission verhindern. Ziel unserer Studie war es, die Umsetzung der 2015 in den Mutterschaftsrichtlinien vorgeschriebenen Dokumentation zur Beratung zum HIV-Test und dessen Durchführung zu untersuchen. Methodik Von Juni bis Oktober 2020 wurde an der Universitätsfrauenklinik Bonn die Dokumentation zum HIV-Screening in Mutterpässen überprüft und Schwangere anhand eines anonymen Fragebogens zum HIV-Test und ihrer Einstellung zu einem universellen Screening befragt. Ergebnisse Von 401 analysierten Mutterpässen war in 11% die Dokumentation unvollständig: in 8% war keine Dokumentation zur Beratung oder Durchführung des HIV-Tests erfolgt, in 3% war nur die Beratung dokumentiert. In den Fragebögen (n=291) gaben 47% der Schwangeren an, dass keine Beratung erfolgt oder erinnerlich sei. 90% der Frauen unterstützten die Durchführung eines HIV-Testes in der Schwangerschaft, 9% waren unsicher, 1% lehnten diesen ab. 55% würden die Umstellung der aktuellen „opt-in“ zur „opt-out“-Screening-Strategie befürworten. Zusammenfassung Die Dokumentation der Beratung und Durchführung des HIV-Tests in der Schwangerschaft war in 11% unvollständig, fast die Hälfte der Mütter berichten, dass eine Beratung nicht erfolgt oder erinnerlich sei. Neue Strategien der Hebammen und Frauenärzt*innen müssen entwickelt werden, um eine universelle HIV-Testung der Schwangeren zu erreichen und in Richtung null HIV-Mutter-Kind-Transmission zu gelangen.

BACKGROUND AND AIMS People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

The presence of neutralizing antibodies against SARS-CoV-2 correlates with protection against infection and severe COVID-19 disease courses. Understanding the dynamics of antibody development against the SARS-CoV-2 virus is important for recommendations on vaccination strategies and on control of the COVID-19 pandemic. This study investigates the dynamics and extent of α-Spike-Ab development by different vaccines manufactured by Johnson & Johnson, AstraZeneca, Pfizer-BioNTech and Moderna. On day 1 after vaccination, we observed a temporal low-grade inflammatory response. α-Spike-Ab titers were reduced after six months of vaccination with mRNA vaccines and increased 14 days after booster vaccinations to a maximum that exceeded titers from mild and critical COVID-19 and Long-COVID patients. Within the group of critical COVID-19 patients, we observed a trend for lower α-Spike-Ab titers in the group of patients who survived COVID-19. This trend accompanied higher numbers of pro-B cells, fewer mature B cells and a higher frequency of T follicular helper cells. Finally, we present data demonstrating that past infection with mild COVID-19 does not lead to long-term increased Ab titers and that even the group of previously infected SARS-CoV-2 patients benefit from a vaccination six months after the infection.

We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated persons. Analyzing plasma samples from 39 coronavirus disease 2019 (COVID-19) patients and 11 vaccinated individuals, significant induction of ADCC could be observed over a period of more than 3 months in both vaccinated and recovered individuals. Although plasma antibody concentrations were lower in recovered patients, we found antibodies elicited by natural infection induced a significantly stronger ADCC response compared to those induced by vaccination, which may affect protection conferred by vaccination.

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus (HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBsAg-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145R, P120Q, and Q129P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

Background: De novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD. Methods: This study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates. Findings: 319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m2 (OR: 4·238, 95% CI: 2·078–8·938; p < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362–10·899); p < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370–4·048; p = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315–24·981; p < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12–0·64; p = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101–0·945; p = 0·04). Interpretation: Steatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m2. While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis. Funding: There was no additional funding received for this project. All funders mentioned in the ‘declaration of interests’ section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Several cohorts have shown that long-term tenofovir-containing combination antiretroviral therapy (cART) leads to higher HBsAg seroclearance rates in HIV/HBV coinfected patients vs HBV-monoinfected patients under tenofovir disoproxil fumarate (TDF)-based therapy. We have analysed data on determinants of HBsAg loss in a retrospective multicentric cohort of 359 HIV/HBV coinfected patients. Median CD4 T-cell count at baseline was 359/ul (321-404), CDC stage was C in 20% (n = 70). Most patients (68%) were ART-naïve when TDF- or tenofovir alafenamide (TAF)-containing cART was initiated (baseline). After a median follow-up of 11 years HBsAg loss had occurred in 66/359 (18%) patients. However, patients with stage CDC C (P ≤ .001), lower CD4 gain (P = .043) and not receiving TDF/FTC (P = .008) were less likely to lose HBsAg. Long-term TDF-containing cART appears to achieve higher rates of HBsAg seroclearance compared to published data for HBV monoinfected subjects. However, late presentation for HIV and poor immune recovery significantly impair HBV seroconversion rates.