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Author(s): Kathryn S. Hensley, Marlou J. Jongkees, Daryl Geers, Corine H. GeurtsvanKessel, Yvonne M. Mueller, Virgil A. S. H. Dalm, Grigorios Papageorgiou, Hanka Steggink, Alicja Gorska, Susanne Bogers, Jan G. [...]

Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH. Methods and findings We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.COV2.S vaccines in adult PLWH without prior COVID-19, and compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response, and reactogenicity. Between 14 February and 7 September 2021, 1,154 PLWH (median age 53 [IQR 44-60] years, 85.5% male) and 440 controls (median age 43 [IQR 33-53] years, 28.6% male) were included in the final analysis. Of the PLWH, 884 received BNT162b2, 100 received mRNA-1273, 150 received ChAdOx1-S, and 20 received Ad26.COV2.S. In the group of PLWH, 99% were on antiretroviral therapy, 97.7% were virally suppressed, and the median CD4+ T-cell count was 710 cells/[mu]L (IQR 520-913). Of the controls, 247 received mRNA-1273, 94 received BNT162b2, 26 received ChAdOx1-S, and 73 received Ad26.COV2.S. After mRNA vaccination, geometric mean antibody concentration was 1,418 BAU/mL in PLWH (95% CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV status remained associated with a decreased response (0.607, 95% CI 0.508-0.725, p 300 BAU/mL, whilst in PLWH this response rate was 93.6%. In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+ T-cell count 250-500 cells/[mu]L (2.845, 95% CI 1.876-4.314, p 500 cells/[mu]L (2.936, 95% CI 1.961-4.394, p 50 copies/mL was associated with a reduced response (0.454, 95% CI 0.286-0.720, p = 0.001). Increased IFN-[gamma], CD4+ T-cell, and CD8+ T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation-induced marker assays, comparable to controls. Reactogenicity was generally mild, without vaccine-related serious adverse events. Due to the control of vaccine provision by the Dutch National Institute for Public Health and the Environment, there were some differences between vaccine groups in the age, sex, and CD4+ T-cell counts of recipients. Conclusions After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH compared to HIV-negative controls. To reach and maintain the same serological responses as HIV-negative controls, additional vaccinations are probably required. Trial registration The trial was registered in the Netherlands Trial Register (NL9214). https://www.trialregister.nl/trial/9214., Author(s): Kathryn S. Hensley 1, Marlou J. Jongkees 1, Daryl Geers 2, Corine H. GeurtsvanKessel 2, Yvonne M. Mueller 3, Virgil A. S. H. Dalm 3,4, Grigorios Papageorgiou 5, Hanka [...]

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV. [ABSTRACT FROM AUTHOR]

Background: The COVIH-study is a prospective SARS-CoV-2 vaccination study in 1154 people with HIV (PWH), of whom 14% showed a reduced or absent antibody response after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders.Methods: Consenting hyporesponders received an additional 100µg mRNA-1273 vaccination. The primary endpoint was the increase in antibodies 28 days thereafter. Secondary endpoints were the correlation between participant characteristics and antibody response, levels of neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity.Results: Of the 66 participants, 40 previously received two doses ChAdOx1-S, 22 two doses BNT162b2, and four a single dose Ad26.COV2.S. The median age was 63[IQR:60-66], 86% were male, pre-vaccination CD4+ T-cell count was median 650/μL[IQR:423-941] and 96% had HIV-RNA < 50 copies/mL. The mean S1-specific antibody level increased from 35 BAU/mL (95%CI:24-46) to 4317 BAU/mL (95%CI:3275-5360) post-vaccination (p < 0.0001). Of all participants, 97% showed an adequate response (>300 BAU/mL) and the 45 antibody negative participants all seroconverted (>33.8 BAU/mL). A significant increase in the proportion of PWH with detectable ancestral S-specific CD4+ T-cells (p = 0.04) and S-specific B-cells (p = 0.02) was observed.Conclusion: An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. [ABSTRACT FROM AUTHOR]

To improve sexual health among people living with HIV, sexual health should be addressed during consultations in routine HIV care. The aim of the present study was to investigate to what extent Sexual Health Counselling (SHC) is incorporated into routine Dutch HIV care and to explore differences between physicians and nurses in their practices and views regarding SHC. A cross-sectional survey was conducted among all HIV physicians (N=110) and HIV nurses (N=82) in the Netherlands. A questionnaire assessed socio-demographic characteristics, current SHC practice, topics addressed, and factors associated with engaging in SHC. The response rate was 53.6% (N=59) among physicians and 60.0% (N=40) among nurses. SHC was performed by 26.1% of physicians and 83.9% of nurses (Χ² (1) = 27.68, p<.001). The most frequently reported barrier for SHC was the presence of a third party, endorsed by 50.9% of physicians and 60.4% of nurses. Nurses were more likely to address issues related to sexual wellbeing, while physicians mainly discussed medical topics. While, both HIV physicians and nursed felt responsible for providing SHC, nurses were more likely to address SHC that physicians. There is scope for improving SHC for PLHIV through a multidisciplinary approach based on clear guidelines for physicians and nurses. [ABSTRACT FROM AUTHOR]

Objectives There is a global increase in infections caused by Gram-negative bacteria. The majority of research is on bacteremic Gram-negative infections (GNI), leaving a knowledge gap on the burden of non-bacteremic GNI. Our aim is to describe characteristics and determine the burden of bacteremic and non-bacteremic GNI in hospitalized patients in the Netherlands. Methods We conducted a prospective cohort study of patients in eight hospitals with microbiologically confirmed GNI, between June 2013 and November 2015. In each hospital the first five adults meeting the eligibility criteria per week were enrolled. We estimated the national incidence and mortality of GNI by combining the cohort data with a national surveillance database for antimicrobial resistance. Results 1,954 patients with GNI were included of which 758 (39%) were bloodstream infections (BSI). 243 GNI (12%) involved multi-drug resistant pathogens. 30-day mortality rate was 11.1% (n = 217) Estimated national incidences of non-bacteremic GNI and bacteremic GNI in hospitalized adults were 74 (95% CI 58 - 89) and 86 (95% CI 72-100) per 100,000 person years, yielding estimated annual numbers of 30-day all-cause mortality deaths of 1,528 (95% CI 1,102-1,954) for bacteremic and 982 (95% CI 688 - 1,276) for non-bacteremic GNI. Conclusion GNI form a large mortality burden in a low-resistance country. A third of the associated mortality occurs after non-bacteremic GNI., Competing Interests: Conflicts of Interest None reported., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Antibiotic resistance in Gram-negative bacteria has been associated with increased mortality. This was demonstrated mostly for third-generation cephalosporin-resistant (3GC-R) Enterobacterales bacteraemia in international studies. Yet, the burden of resistance specifically in the Netherlands and created by all types of Gram-negative infection has not been quantified. We therefore investigated the attributable mortality of antibiotic resistance in Gram-negative infections in the Netherlands., Methods: In eight hospitals, a sample of Gram-negative infections was identified between 2013 and 2016, and separated into resistant and susceptible infection cohorts. Both cohorts were matched 1:1 to non-infected control patients on hospital, length of stay at infection onset, and age. In this parallel matched cohort set-up, 30-day mortality was compared between infected and non-infected patients. The impact of resistance was then assessed by dividing the two separate risk ratios (RRs) for mortality attributable to Gram-negative infection., Results: We identified 1954 Gram-negative infections, of which 1190 (61%) involved Escherichia coli, 210 (11%) Pseudomonas aeruginosa, and 758 (39%) bacteraemia. Resistant Gram-negatives caused 243 infections (12%; 189 (78%) 3GC-R Enterobacterales, nine (4%) multidrug-resistant P. aeruginosa, no carbapenemase-producing Enterobacterales). Subsequently, we matched 1941 non-infected controls. After adjustment, point estimates for RRs comparing mortality between infections and controls were similarly higher than 1 in case of resistant infections and susceptible infections (1.42 (95% confidence interval 0.66-3.09) and 1.32 (1.06-1.65), respectively). By dividing these, the RR reflecting attributable mortality of resistance was calculated as 1.08 (0.48-2.41)., Conclusions: In the Netherlands, antibiotic resistance did not increase 30-day mortality in Gram-negative infections., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In 1%-5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the diagnostic value of 18 F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up. Methods: All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one 18 F-FDG PET/CT scan was obtained. Clinical data and results from 18 F-FDG PET/CT at diagnosis and during follow-up were collected. 18 F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system. Results: In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all 18 F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever-related mortality rate in patients with and without vascular infection based on 18 F-FDG PET/CT was 23.8% and 2.1%, respectively ( P = 0.001). When 18 F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of 18 F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of 18 F-FDG PET/CT scans resulted in treatment modification. Conclusion: 18 F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Aims: We aimed to elucidate facilitators and barriers that HIV nurses experience in discussing sexual risk behaviour with HIV-positive men who have sex with men, using variables from a previous qualitative study and the theory of planned behaviour., Background: HIV-positive men who have sex with men are frequently diagnosed with sexually transmitted infections, which can be reduced if HIV nurses discuss sexual risk behaviour., Design: An online questionnaire was disseminated in April 2015 among all HIV nurses in the Netherlands., Methods: We assessed variables, such as attitudes, shame, ability, knowledge and time concerns. A regression analysis was conducted with "intention to discuss sexual risk behaviour" as an outcome variable., Results: The questionnaire was completed by 60 of 79 HIV nurses. Overall, participants reported high intentions to discuss sexual risk behaviour, and 38% of the variance was explained by attitude, sexual preference, knowing ways to introduce the topic and experiencing enough time or viewing it as a priority. In addition, high intenders significantly differed from low intenders in "experienced shame," "relation with patients," "non-verbal communication," "subjective norm" and "knowledge.", Conclusion: Improving sexual health in HIV care translates into improving opportunities and the facilitating factors in initiating the discussion of sexual risk behaviour rather than removing barriers HIV nurses experience. Interventions should mainly focus on improving the HIV nurses' perceived ability to initiate the topic of sexual risk behaviour and to utilize the jargon and terminology that is commonly used among men who have sex with men., (© 2017 John Wiley & Sons Ltd.)