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Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by human sera is a strong correlate of protection against symptomatic and severe Coronavirus Disease 2019 (COVID-19). The emergence of antigenically distinct SARS-CoV-2 variants of concern (VOCs) and the relatively rapid waning of serum antibody titers, however, raises questions about the sustainability of serum protection. In addition to serum neutralization, other antibody functionalities and the memory B cell (MBC) response are suggested to help maintaining this protection. In this study, we investigate the breadth of spike (S) protein-specific serum antibodies that mediate effector functions by interacting with Fc-gamma receptor IIa (FcγRIIa) and FcγRIIIa, and of the receptor binding domain (RBD)-specific MBCs, following a primary SARS-CoV-2 infection with the D614G, Alpha, Beta, Gamma, Delta, Omicron BA.1 or BA.2 variant. Irrespectively of the variant causing the infection, the breadth of S protein-specific serum antibodies that interact with FcγRIIa and FcγRIIIa and the RBD-specific MBC responses exceeded the breadth of serum neutralization, although the Alpha-induced B cell response seemed more strain-specific. Between VOC groups, both quantitative and qualitative differences in the immune responses were observed, suggesting differences in immunogenicity. Overall, this study contributes to the understanding of protective humoral and B cell responses in the light of emerging antigenically distinct VOCs, and highlights the need to study the immune system beyond serum neutralization to gain a better understanding of the protection against emerging variants.

BackgroundAn increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP.Methods and findingsThe Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals.ConclusionsIn this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time.Trial registrationThe study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.

Abstract Introduction The HIV and hepatitis B virus (HBV) epidemics are interconnected with shared routes of transmission and specific antiviral drugs that are effective against both viruses. Nearly, 300 million people around the world live with chronic HBV, many of whom are from priority populations who could benefit from HIV prevention services. Oral pre‐exposure prophylaxis (PrEP) for HIV has implications in the prevention and treatment of HBV infection, but many people at increased risk of HIV acquisition may instead prefer long‐acting formulations of PrEP, which are currently not active against HBV. Discussion People at increased risk for HIV acquisition may also be at risk for or already be living with HBV infection. Oral PrEP with tenofovir is effective in preventing both HIV and HBV, and tenofovir is also the recommended treatment for chronic HBV infection. Although implementation of oral PrEP has been challenging in sub‐Saharan Africa, investments in its scale‐up could secondarily reduce the clinical impact of HBV. Long‐acting PrEP, including injectable medicines and implantable rings, may overcome some of the implementation challenges associated with oral PrEP, such as daily pill burden, adherence challenges and stigma; however, current formulations of long‐acting PrEP do not have activity against HBV replication. Ideally, PrEP programmes would offer both oral and long‐acting formulations with HBV screening to optimize HIV prevention services and HBV prevention and care, when appropriate. People who are not immune to HBV would benefit from being vaccinated against HBV before initiating long‐acting PrEP. People who remain non‐immune to HBV despite vaccination may benefit from being offered oral, tenofovir‐based PrEP given its potential for HBV PrEP. People using PrEP and living with HBV who are not linked to dedicated HBV care would also benefit from laboratory monitoring at PrEP sites to ensure safety when using and after stopping tenofovir. PrEP programmes are ideal venues to offer HBV screening, HBV vaccination for people who are non‐immune and treatment with tenofovir‐based PrEP for people with indications for HBV therapy. Conclusions Long‐acting PrEP holds promise for reducing HIV incidence, but its implications for the HBV epidemic, particularly in sub‐Saharan Africa, should not be overlooked.

Background: After the global COVID-19 crisis, understanding post-infectious immunity and vaccine efficacy remains crucial. This study aims to assess anti-SARS-CoV-2 immunity through a quantitative analysis of anti-receptor-binding domain (RBD) antibodies and rapid functional testing of the neutralizing humoral response. Methods: A retrospective analysis was conducted on samples from various cohorts, including partially vaccinated, fully vaccinated, post-COVID/no-vaccination, and post-COVID/vaccination individuals with various immune-competency statuses. The anti-RBD antibodies were measured using an automated chemiluminescence assay, while the neutralizing antibodies’ (NAbs’) activity was assessed through the lateral flow ichroma COVID-19 nAb test (LFT), a surrogate neutralization assay. Results: The analysis revealed various levels of anti-RBD antibodies and seroneutralization responses across cohorts, with the post-COVID/vaccination group demonstrating the most robust protection. A correlation between anti-RBD antibodies and seroneutralization was observed, albeit with varying strength depending on the subgroup analyzed. Longitudinal assessment following natural infection showed an initial surge followed by a decline in both measures. A cutoff of 3.0 log10 BAU/mL was established to predict significant seroneutralization. Conclusions: The ichroma™ COVID-19 nAb test displayed high specificity and emerged as a valuable tool for monitoring anti-SARS-CoV-2 immunity. These findings contribute to understand the antibody response dynamics and underscore the potential of rapid tests in predicting protection against SARS-CoV-2 infection.

Abstract Background Although risk factors for differences in SARS-CoV-2 infections between migrant and non-migrant populations in high income countries have been identified, their relative contributions to these SARS-CoV-2 infections, which could aid in the preparation for future viral pandemics, remain unknown. We investigated the relative contributions of pre-pandemic factors and intra-pandemic activities to differential SARS-CoV-2 infections in the Netherlands by migration background (Dutch, African Surinamese, South-Asian Surinamese, Ghanaians, Turkish, and Moroccan origin). Methods We utilized pre-pandemic (2011–2015) and intra-pandemic (2020–2021) data from the HELIUS cohort, linked to SARS-CoV-2 PCR test results from Public Health Service of Amsterdam (GGD Amsterdam). Pre-pandemic factors included socio-demographic, medical, and lifestyle factors. Intra-pandemic activities included COVID-19 risk aggravating and mitigating activities such as physical distancing, use of face masks, and other similar activities. We calculated prevalence ratios (PRs) in the HELIUS population that was merged with GGD Amsterdam PCR test data using robust Poisson regression (SARS-CoV-2 PCR test result as outcome, migration background as predictor). We then obtained the distribution of migrant and non-migrant populations in Amsterdam as of January 2021 from Statistics Netherlands. The migrant populations included people who have migrated themselves as well as their offspring. We used PRs and the population distributions to calculate population attributable fractions (PAFs) using the standard formula. We used age and sex adjusted models to introduce pre-pandemic factors and intra-pandemic activities, noting the relative changes in PAFs. Results From 20,359 eligible HELIUS participants, 8,595 were linked to GGD Amsterdam PCR test data and included in the study. Pre-pandemic socio-demographic factors (especially education, occupation, and household size) resulted in the largest changes in PAFs when introduced in age and sex adjusted models (up to 45%), followed by pre-pandemic lifestyle factors (up to 23%, especially alcohol consumption). Intra-pandemic activities resulted in the least changes in PAFs when introduced in age and sex adjusted models (up to 16%). Conclusion Interventions that target pre-pandemic socio-economic status and other drivers of health inequalities between migrant and non-migrant populations are urgently needed at present to better prevent infection disparities in future viral pandemics.

Objectives Detailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes.Methods We developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC).Results Model-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies.Conclusions We simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.

Abstract Background As highly effective therapy against hepatitis C virus (HCV) infection is available with rapid uptake, there is newfound optimism for HCV elimination. Nevertheless, certain key populations have a high risk of HCV reinfection, in particular men who have sex with men (MSM) in Western European countries. Modelling data indicate that HCV elimination will not be feasible without reduction in risk behaviour, thus supporting the need for effective interventions aimed at reducing risk behaviour and preventing reinfections in MSM. Methods The ICECREAM study is an international, multi-centred, phase 2, 3-arm randomised trial comparing run-in and intervention periods enrolling MSM with a history of a cured or spontaneously cleared HCV infection. Individuals are followed in routine care for 6 months (i.e. run-in period) and then randomly allocated (1:1:1) to one of the following: a tailored, interactive online risk-reduction behavioural intervention, a validated home-based HCV-RNA self-sampling test service using dried blood spots, or a combination of both. After randomisation, individuals are followed every 6 months until 18 months (i.e. intervention period). Interventions are delivered in addition to standard of care. Online questionnaire measuring risk behaviour over the past 6 months is administered at every visit. The primary outcome is the proportion at risk of HCV infection during run-in versus intervention periods assessed by using the HCV-MOSAIC risk score. The risk score consists of six self-reported HCV-related risk behaviours. Secondary outcomes include incidence of HCV reinfection, changes in the individual risk behaviour items and changes in sexual well-being since changes in sexual behaviour may have an impact on sexual experience. Two hundred forty-six MSM aged 18 years or older will be invited to participate. Discussion The ICECREAM study is a trial aimed at establishing interventions that could effectively decrease the incidence of HCV re-infection in MSM with a previous HCV infection. By offering an online behavioural risk-reduction intervention and HCV-RNA self-sampling, both of which are aimed to influence risk behaviour, we are able to provide products to at-risk MSM that could further reduce population-level HCV incidence and ultimately help reach HCV micro-elimination. Trial registration ClinicalTrials.gov NCT04156945. Registered on November 8, 2019

Summary: Antiretroviral therapy (ART) has dramatically lengthened lifespan among people with HIV (PWH), but this population experiences heightened rates of inflammation-related comorbidities. HIV-associated inflammation is linked with an altered microbiome; whether such alterations precede inflammation-related comorbidities or occur as their consequence remains unknown. We find that ART-treated PWH exhibit depletion of gut-resident bacteria that produce short-chain fatty acids (SCFAs)—crucial microbial metabolites with anti-inflammatory properties. Prior reports establish that fecal SCFA concentrations are not depleted in PWH. We find that gut-microbiota-mediated SCFA production capacity is better reflected in serum than in feces and that PWH exhibit reduced serum SCFA, which associates with inflammatory markers. Leveraging stool and serum samples collected prior to comorbidity onset, we find that HIV-specific microbiome alterations precede morbidity and mortality in ART-treated PWH. Among these microbiome alterations, reduced microbiome-mediated conversion of lactate to propionate precedes mortality in PWH. Thus, gut microbial fiber/lactate conversion to SCFAs may modulate HIV-associated comorbidity risk.

BackgroundDaily and event-driven HIV pre-exposure prophylaxis (PrEP) with oral tenofovir-emtricitabine is highly effective to prevent HIV in men who have sex with men (MSM). PrEP care generally consists of in-clinic monitoring every 3 months that includes PrEP dispensing, counseling, and screening for HIV and sexually transmitted infections (STIs). However, the optimal frequency for monitoring remains undetermined. Attending a clinic every 3 months for monitoring may be a barrier for PrEP. Online-mediated PrEP care and reduced frequency of monitoring may lower this barrier. ObjectiveThe primary objective of this study is to establish the noninferiority of online PrEP care (vs in-clinic care) and monitoring every 6 months (vs every 3 months). The secondary objectives are to (1) examine differences between PrEP care modalities regarding incidences of STIs, HIV infection, and hepatitis C virus infection; retention in PrEP care; intracellular tenofovir-diphosphate concentration; and satisfaction, usability, and acceptability of PrEP care modalities; and (2) evaluate associations of these study outcomes with sociodemographic, behavioral, and psychological characteristics. MethodsThis study is a 2×2 factorial, 4-arm, open-label, multi-center, randomized, controlled, noninferiority trial. The 4 arms are (1) in-clinic monitoring every 3 months, (2) in-clinic monitoring every 6 months, (3) online monitoring every 3 months, and (4) online monitoring every 6 months. The primary outcome is a condomless anal sex act with a casual partner not covered or insufficiently covered by PrEP (ie, “unprotected act”) as a proxy for HIV infection risk. Eligible individuals are MSM, and transgender and gender diverse people aged ≥18 years who are eligible for PrEP care at 1 of 4 participating sexual health centers in the Netherlands. The required sample size is 442 participants, and the planned observation time is 24 months. All study participants will receive access to a smartphone app, which contains a diary. Participants are requested to complete the diary on a daily basis during the first 18 months of participation. Participants will complete questionnaires at baseline and 6, 12, 18, and 24 months. Dried blood spots will be collected at 6 and 12 months for assessment of intracellular tenofovir-diphosphate concentration. Incidence rates of unprotected acts will be compared between the online and in-clinic arms, and between the 6-month and 3-month arms. Noninferiority will be concluded if the upper limit of the 2-sided 97.5% CI of the incidence rate ratio is

Abstract Introduction Daily and event‐driven oral pre‐exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use irrespective of the chosen PrEP regimens among men who have sex with men (MSM). Methods Using data from a mobile, web‐based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be‐PrEP‐ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event‐driven oral PrEP every 3 months. We used group‐based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories. Results We included 516 MSM (n = 322 AMPrEP; n = 194 Be‐PrEP‐ared), of whom 24% chose event‐driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow‐up (median = 508 days [IQR = 429−511]). Four distinct PrEP use trajectories were identified: ≤2 tablets per week (“low frequency,” 12% of the total population), 4 tablets per week (“variable,” 17%), “almost daily” (31%) and “always daily” (41%). Compared to participants with “low frequency” PrEP use, participants with “variable” (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.04−4.60) and “almost daily” PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27−5.49). “Almost daily” PrEP users were more often employed (OR = 6.76, 95% CI = 2.10−21.75) and were younger compared to participants with “low frequency” PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with “low frequency” PrEP use compared to the other groups (all p

BackgroundIn hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. ObjectiveOur goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. MethodsThis is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. ResultsAs of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. ConclusionsThis study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. Trial RegistrationClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359 International Registered Report Identifier (IRRID)DERR1-10.2196/48183

ABSTRACT Few studies have comprehensively compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced and hybrid B- and T-cell responses in people with HIV (PWH) to those in comparable controls without HIV. We included 195 PWH and 246 comparable controls from the AGEhIV COVID-19 substudy. A positive nucleocapsid antibody (INgezim IgA/IgM/IgG) or self-reported PCR test defined prior SARS-CoV-2 infection. SARS-CoV-2 anti-spike (anti-S) IgG titers and anti-S IgG production by memory B cells were assessed. Neutralizing antibody titers were determined in a subset of participants. T-cell responses were assessed by gamma interferon (IFN-γ) release and activation-induced marker assay. We estimated mean differences in postvaccination immune responses (β) between levels of determinants. Anti-S IgG titers and anti-S IgG production by memory B cells were not different between PWH and controls. Prior SARS-CoV-2 infection (β = 0.77), receiving mRNA vaccine (β = 0.56), female sex (β = 0.24), fewer days between last vaccination and sampling (β = 0.07), and a CD4/CD8 ratio of

We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM with HIV/HCV-coinfection who became reinfected (cases, n = 27) or not (controls, n = 76) during follow-up. The overall predictive capacity of the score was assessed using the area under the receiver operating characteristic (AUROC) curve. The effects of covariates on the receiver operating characteristic (ROC) curve were assessed using parametric ROC regression. The score cut-off validated for primary early infection (≥2.0) was used, from which the sensitivity and specificity were calculated. The AUROC was 0.74 (95% confidence interval (CI) = 0.63–0.84). Group sex significantly increased the predictive capacity. Using the validated cut-off, sensitivity was 70.4% (95%CI = 49.8–86.2%) and specificity was 59.2% (95%CI: 47.3–70.4%). External validation from a cohort of 25 cases and 111 controls, all MSM with HIV, resulted in a sensitivity of 44.0% (95%CI = 24.4–65.1) and specificity of 71.2% (95%CI = 61.8–79.4). The HCV-MOSAIC risk score may be useful for identifying individuals at risk of HCV reinfection. In sexual health or HIV-care settings, this score could help guide HCV-RNA testing in MSM with a prior HCV infection.

Summary: Background: Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a “treatment as prevention” (TasP) effect. We assessed changes in primary HCV incidence following DAA access among people living with HIV (PLHIV). Methods: We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010–2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods. Findings: Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio [IRR] = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89). Interpretation: Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030. Funding: This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902).

BackgroundThere is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of pulmonary impairment across the full spectrum of COVID-19 severity over time.MethodsIn a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression.FindingsBetween May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (pInterpretationThe prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities.

This study identified subgroups of sexual behaviors associated with increased STI/HIV risk among those eligible for but not using pre-exposure prophylaxis (PrEP) in order to improve PrEP uptake and prioritization in the context of restricted capacity. We used data from sexual health centers (SHCs) in the Netherlands, including all visits of eligible but non-PrEP using men who have sex with men (MSM), men who have sex with men and women (MSMW) and transgender persons between July 2019 (start of the Dutch national PrEP pilot (NPP)) and June 2021. Using latent class analysis (LCA), we identified classes of sexual behaviors (number of partners, chemsex, group sex and sex work) and explored whether these classes were associated with STI diagnosis and sociodemographics. Across 45,582 visits of 14,588 eligible non-PrEP using individuals, the best fitting LCA model contained three classes of sexual behaviors. Classes were distinguished by seldomly reported sexual behaviors (class 1; 53.5%, n = 24,383), the highest proportions of ≥6 partners and group sex (class 2; 29.8%, n = 13,596), and the highest proportions of chemsex and sex work (class 3; 16.7% of visits, n = 7,603). Visits in classes 2 and 3 (vs. class 1) were significantly more often with individuals who were diagnosed with an STI, older (≥36 vs. ≤35 years), MSMW (vs. MSM), and visiting an urban (vs. non-urban) SHC; while these visits were significantly less often with individuals from an STI/HIV endemic area. The percentage of visits at which an STI was diagnosed was 17.07% (n = 4,163) in class 1, 19.53% (n = 2,655) in class 2 and 25.25% (n = 1,920) in class 3. The highest risk of STI, and thereby HIV, was in those engaging in specific subgroups of sexual behavior characterized by frequently reporting multiple partners, group sex, sex work or chemsex. PrEP uptake should be encouraged and prioritized for these individuals.

BackgroundIn the Netherlands, general practitioners (GPs) play a key role in HIV testing. However, the proportion of people diagnosed with late-stage HIV remains high, and opportunities for earlier diagnosis are being missed. We implemented an educational intervention to improve HIV and STI testing in primary care in Amsterdam, the Netherlands.MethodsGPs were invited to participate in an educational program between 2015 and 2020, which included repeat sessions using audit and feedback and quality improvement plans. Data on HIV, chlamydia and gonorrhoea testing by GPs were collected from 2011 through 2020. The primary outcome was HIV testing frequency, which was compared between GPs before and after participation using Poisson regression. Secondary outcomes were chlamydia and gonorrhoea testing frequencies, and positive test proportions. Additional analyses stratified by patient sex and age were done.FindingsGPs after participation performed 7% more HIV tests compared to GPs before participation (adjusted relative ratio [aRR] 1.07, 95%CI 1.04-1.09); there was no change in the proportion HIV positive tests (aRR 0.87, 95%CI 0.63-1.19). HIV testing increased most among patients who were female and ≤19 or 50-64 years old. After participation, HIV testing continued to increase (aRR 1.02 per quarter, 95%CI 1.01-1.02). Chlamydia testing by GPs after participation increased by 6% (aRR 1.06, 95%CI 1.05-1.08), while gonorrhoea testing decreased by 2% (aRR 0.98, 95%CI 0.97-0.99). We observed increases specifically in extragenital chlamydia and gonorrhoea testing.ConclusionsThe intervention was associated with a modest increase in HIV testing among GPs after participation, while the proportion positive HIV tests remained stable. Our results suggest that the intervention yielded a sustained effect.

Summary: Background: Indicator-condition (IC) guided HIV testing is a feasible and cost-effective strategy to identify undiagnosed people living with HIV (PLHIV), but remains insufficiently implemented. We aimed to promote IC-guided HIV testing in seven ICs. Methods: Relevant departments in five hospitals of the Amsterdam region participated. HIV testing among adult patients without known HIV infection but with an IC was assessed using electronic health records during pre-intervention (January 2015–June 2020) and intervention (July 2020–June 2021) periods. The multifaceted intervention included audit and feedback. The primary endpoint was HIV testing ≤3 months before or after IC diagnosis and the effect of the intervention was evaluated using segmented Poisson regression. Findings: Data from 7986 patients were included, of whom 6730 (84·3%) were diagnosed with an IC in the pre-intervention period and 1256 (15·7%) in the intervention period. The proportion HIV tested ≤3 months before or after IC diagnosis increased from 36.8% to 47.0% (adjusted risk ratio [RR]= 1.16, 95% CI=1.03–1.30, p=0.02). For individual ICs, we observed significant increases in HIV testing among patients with cervical cancer or intraepithelial neoplasia grade 3 (adjusted RR=3.62, 95% CI=1.93–6.79) and peripheral neuropathy (adjusted RR=2.27 95% CI=1.48–3.49), but not the other ICs. Eighteen of 3068 tested patients were HIV positive (0.6%). Interpretation: Overall IC-guided testing improved after the intervention, but not for all ICs. Variations in effect by IC may have been due to variations in implemented developments, but the effect of separate elements could not be assessed. Funding: HIV Transmission Elimination Amsterdam (H-TEAM) initiative, Aidsfonds (grant number: P-42702).

BackgroundHepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV.Materials and methodsWe included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models.Results61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4–5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2–8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV.ConclusionPersistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment.

Abstract Background Late presentation remains a key barrier towards controlling the HIV epidemic. Indicator conditions (ICs) are those that are AIDS-defining, associated with a prevalence of undiagnosed HIV > 0.1%, or whose clinical management would be impeded if an HIV infection were undiagnosed. IC-guided HIV testing is an effective strategy in identifying undiagnosed HIV, but opportunities for earlier HIV diagnosis through IC-guided testing are being missed. We present a protocol for an interventional study to improve awareness of IC-guided testing and increase HIV testing in patients presenting with ICs in a hospital setting. Methods We designed a multicentre interventional study to be implemented at five hospitals in the region of Amsterdam, the Netherlands. Seven ICs were selected for which HIV test ratios (proportion of patients with an IC tested for HIV) will be measured: tuberculosis, cervical/vulvar cancer or high-grade cervical/vulvar dysplasia, malignant lymphoma, hepatitis B and C, and peripheral neuropathy. Prior to the intervention, a baseline assessment of HIV test ratios across ICs will be performed in eligible patients (IC diagnosed January 2015 through May 2020, ≥18 years, not known HIV positive) and an assessment of barriers and facilitators for HIV testing amongst relevant specialties will be conducted using qualitative (interviews) and quantitative methods (questionnaires). The intervention phase will consist of an educational intervention, including presentation of baseline results as competitive graphical audit and feedback combined with discussion on implementation and opportunities for improvement. The effect of the intervention will be assessed by comparing HIV test ratios of the pre-intervention and post-intervention periods. The primary endpoint is the HIV test ratio within ±3 months of IC diagnosis. Secondary endpoints are the HIV test ratio within ±6 months of diagnosis, ratio ever tested for HIV, HIV positivity percentage, proportion of late presenters and proportion with known HIV status prior to initiating treatment for their IC. Discussion This protocol presents a strategy aimed at increasing awareness of the benefits of IC-guided testing and increasing HIV testing in patients presenting with ICs in hospital settings to identify undiagnosed HIV in Amsterdam, the Netherlands. Trial registration Dutch trial registry: NL7521 . Registered 14 February 2019.

Introduction It is unclear what role daughters play in the decision-making process regarding HPV vaccination. Therefore, we explored the impact of HPV vaccination intention among parents and their 12–13 year-old daughters on HPV vaccination uptake. Methods In February 2014 parents/guardians and their 12–13 year-old daughters were invited to complete a questionnaire about socio-psychological determinants of the decision-making process regarding HPV vaccination. Vaccination status of the daughter was retrieved from the national vaccination database after the last possible vaccination date in 2014. The association between HPV vaccination uptake and intention, and determinants of intention, was jointly assessed using a generalized structural equation model, stratified by origin of parents (Dutch versus non-Dutch). Results In total, 273 Dutch parent-daughter dyads and 165 non-Dutch dyads were analyzed for this study. HPV vaccination uptake was 90% (246/273) and 84% (139/165) in the Dutch and non-Dutch group, respectively. In the Dutch group, high parental intention (β = 2.3, 95%CI 1.2–3.3) and high daughters’ intention (β = 1.5, 95%CI 0.41–2.6) were significantly associated with HPV vaccination uptake. In the non-Dutch group, high daughters’ intention (β = 1.2, 95%CI 0.16–2.2) was significantly associated with HPV vaccination, but high parental intention was not (β = 0.52, 95%CI −0.47–1.5). Attitude was the most prominent socio-psychological determinant associated with vaccination intention among all groups. Conclusion In the non-Dutch group, only daughters’ intention was significantly associated with HPV vaccination uptake, whereas in the Dutch group both the parents’ and the daughters’ intention were significantly associated with uptake. The role of the child in the decision-making process might need to be taken into account when developing new interventions focused on increasing HPV vaccination uptake, especially among individuals of non-Dutch origin.

Summary: Background: Surveillance data in high-income countries have reported more frequent SARS-CoV-2 diagnoses in ethnic minority groups. We examined the cumulative incidence of SARS-CoV-2 and its determinants in six ethnic groups in Amsterdam, the Netherlands. Methods: We analysed participants enrolled in the population-based HELIUS cohort, who were tested for SARS-CoV-2-specific antibodies and answered COVID-19-related questions between June 24-October 9, 2020 (after the first wave) and November 23, 2020-March 31, 2021 (during the second wave). We modelled SARS-CoV-2 incidence from January 1, 2020-March 31, 2021 using Markov models adjusted for age and sex. We compared incidence between ethnic groups over time and identified determinants of incident infection within ethnic groups. Findings: 2,497 participants were tested after the first wave; 2,083 (83·4%) were tested during the second wave. Median age at first visit was 54 years (interquartile range=44–61); 56·6% were female. Compared to Dutch-origin participants (15·9%), cumulative SARS-CoV-2 incidence was higher in participants of South-Asian Surinamese (25·0%; adjusted hazard ratio [aHR]=1·66; 95%CI=1·16–2·40), African Surinamese (28·9%, aHR=1·97; 95%CI=1·37–2·83), Turkish (37·0%; aHR=2·67; 95%CI=1·89–3·78), Moroccan (41·9%; aHR=3·13; 95%CI=2·22–4·42), and Ghanaian (64·6%; aHR=6·00; 95%CI=4·33–8·30) origin. Compared to those of Dutch origin, differences in incidence became wider during the second versus first wave for all ethnic minority groups (all p-values for interaction

Abstract Background The increase of antimicrobial resistance, mainly due to increased antibiotic use, is worrying. Preliminary evidence suggests that antibiotic use differs across ethnic groups in the Netherlands, with higher use in people of non-Dutch origin. We aimed to determine whether appropriate knowledge and use of antibiotics differ by ethnicity and whether knowledge on antibiotics is associated with antibiotic use. Methods We performed a cross-sectional study analyzing baseline data (2011–2015) from a population-based cohort (HELIUS study), which were linked to data from a health insurance register. We included 21,617 HELIUS participants of South-Asian Surinamese, African-Surinamese, Turkish, Moroccan, Ghanaian, and Dutch origin. Fifteen thousand seven participants had available prescription data from the Achmea Health Data-base (AHD) in the year prior to their HELIUS study visit. Participants were asked five questions on antibiotic treatment during influenza-like illness, pneumonia, fever, sore throat and bronchitis, from which higher versus lower antibiotic knowledge level was determined. Number of antibiotic prescriptions in the year prior to the HELIUS study visit was used to determine antibiotic use. Results The percentage of individuals with a higher level of antibiotic knowledge was lower among all ethnic minority groups (range 57 to 70%) compared to Dutch (80%). After correcting for baseline characteristics, including medical conditions, first-generation African Surinamese and Turkish migrants received a significantly lower number of antibiotic prescriptions compared to individuals of Dutch origin. Only second-generation Ghanaian participants received more prescriptions compared to Dutch participants (aIRR 2.09, 95%CI 1.06 to 4.12). Higher level of antibiotic knowledge was not significantly associated with the number of prescriptions (IRR 0.92, 95%CI 0.85 to 1.00). Conclusions Levels of antibiotic knowledge varied between ethnic groups, but a lower level of antibiotic knowledge did not correspond with a higher number of antibiotic prescriptions.

Background & Aims: Data on the prevalence of chronic hepatitis B (HBV) and hepatitis C (HCV) virus infections, including the proportion of individuals aware of infection, are scarce among migrants living in Europe. We estimated the prevalence of past and present HBV and HCV infection, along with their determinants and peoples’ awareness of infection status, among different groups of first-generation migrants and Dutch-origin residents of Amsterdam. Methods: Cross-sectional data of 998 Surinamese (mostly South-Asian and African-Surinamese), 500 Ghanaian, 497 Turkish, 498 Moroccan and 500 Dutch-origin participants from the observational population-based HELIUS study were used. Blood samples of participants were tested for HBV and HCV infection. Infection awareness was determined using records from participants’ general practitioners. Results: Age- and gender-adjusted chronic HBV prevalence was highest among Ghanaian participants (5.4%), followed by Turkish (4.1%), African-Surinamese (1.9%), Moroccan (1.2%), South-Asian Surinamese (0.9%) and Dutch (0.4%) participants. A total of 58.1% of the cases were aware of their infection. In multinomial logistic regression analyses, Ghanaian (adjusted odds ratio [aOR] 42.23; 95% confidence interval [CI] 9.29–192.01), African-Surinamese (aOR 6.16; 95% CI 1.27–29.79), and Turkish (aOR 13.44; 95% CI 2.94–61.39) participants were at increased risk of chronic HBV infection compared with those of Dutch origin. Older participants were also at increased risk (aOR 1.02 per year; 95% CI 1.00–1.05), whereas women were at lower risk (aOR 0.49; 95% CI 0.29–0.83). HCV prevalence was 0.4% (95% CI 0.1–1.3%) among Dutch and African-Surinamese and 0% (95% CI 0.0–0.5%) for each of the other groups; all cases with follow-up data were aware of their infection. Conclusions: Ghanaian, Turkish and African-Surinamese first-generation migrants are at increased risk of chronic HBV infection and many are unaware of their infection, whereas HCV prevalence was low among all ethnic groups. Screening campaigns are urgently warranted and need to consider specific ethnic groups. Lay summary: First-generation migrants of Ghanaian, Turkish and African-Surinamese origin were at increased risk of chronic hepatitis B infection, with most infections occurring in older individuals and males. Since over 40% of people were unaware of their chronic hepatitis B infection, screening of these migrant groups is urgently needed. The proportion of first-generation migrants chronically infected with hepatitis C virus was very low among all groups studied. Keywords: Viral hepatitis, HBV, HCV, migrants, epidemiology, prevalence, population-based, HELIUS study

Summary: Background: The AGEhIV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGEhIV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGEhIV cohort accounting for smoking behaviour and other risk factors. Methods: We obtained pre-bronchodilator spirometry measurements in AGEhIV cohort participants during biennial visits over a median of 5·9 years (IQR 5·7–6·0). Adjusted declines in forced expiratory volume in 1 s (FEV1), FVC, and FEV1/FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV1 and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acid-binding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582. Findings: 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (

Background Migrants are not routinely screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the Netherlands. We estimated the prevalence and determined factors associated with HBV, HCV and/or HIV infections among undocumented migrants and uninsured legal residents. Methods In this cross-sectional study, undocumented migrants and uninsured legal residents were recruited at a non governmental organization (NGO), healthcare facility in the Netherlands and were invited to be tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibodies (anti-HBcAb), HCV-RNA, and anti-HIV antibodies or HIV antigen at a local laboratory. Results Of the 1376 patients invited, 784 (57%) participated. Participants originated from Africa (35%), Asia (30%) and North/South America (30%). 451/784 (58%) participants went to the laboratory for testing. Of participants 30% were HBV exposed (anti-HBcAb-positive), with 27% (n = 119/438, 95% CI 23.1% to 31.6%) having resolved HBV infection (HBsAg-negative) and 2.5% (n = 11/438, 95%CI 1.3% to 4.5%, 64% new infection) having chronic HBV infection (HBsAg-positive). Compared to HBV non-exposed, HBV exposed individuals were older (p = 0.034) and more often originated from Africa (pConclusion Prevalence of chronic HBV, chronic HCV and HIV infections in our study population is higher compared to the Dutch population, thus emphasizing the importance of case finding for these infections through primary care and public health in this specific group of migrants. Screening uptake could be improved by on-site testing.

ObjectivesRecent studies have reported disproportionate weight gain associated with integrase strand transfer inhibitor (INSTI) initiation in antiretroviral therapy(ART)-naive people with HIV (PWH), particularly among black women. We investigated if HIV-positive AGEhIV participants with suppressed viremia switching to INSTI-containing ART experienced more weight gain compared to HIV-positive virally-suppressed non-switching and HIV-negative controls.MethodsIn the AGEhIV cohort, standardized weight measurements were performed biennially. Participants switching to INSTI-containing ART were 1:2:2 propensity score-matched with controls by age, gender, ethnicity and body mass index. Mean weight changes and proportions experiencing >5% or >10% weight gain were compared between study-groups using linear mixed-effects models and logistic regression, respectively.Results121 INSTI-switching participants and 242 participants from each of the control groups were selected. Across groups, median age was 53-55 years, 83-91% were male and 88-93% white. Mean weight change after switch among INSTI-switching participants was +0.14 kg/year (95%CI -0.25, +0.54) and similar among HIV-positive [+0.13 kg/year (95%CI +0.07, +0.33; P = .9)] and HIV-negative [+0.18 kg/year (95%CI 0.00, +0.37; P = .9)] controls. Weight gain >5% occurred in 28 (23.1%) INSTI-switching, 38 HIV-positive (15.7%, P = .085) and 32 HIV-negative controls (13.2%, P = .018). Weight gain >10% was rare.ConclusionsSwitching to INSTI-containing ART in our cohort of predominantly white men on long-term ART was not associated with greater mean weight gain, but >5% weight gain was more common than in controls. These results suggest that not all, but only certain, PWH may be particularly prone to gain a clinically significant amount of weight as a result of switching to INSTI.

As individual sexual behavior is variable over time, the timing of interventions might be vital to reducing HIV transmission. We aimed to investigate transitions between HIV risk levels among men who have sex with men (MSM), and identify determinants associated with behavior change. Participants in a longitudinal cohort study among HIV-negative MSM (Amsterdam Cohort Studies) completed questionnaires about their sexual behavior during biannual visits (2008–2017). Visits were assigned to different HIV risk levels, based on latent classes of behavior. We modelled transitions between risk levels, and identified determinants associated with these transitions at the visit preceding the transition using multi-state Markov models. Based on 7,865 visits of 767 participants, we classified three risk levels: low (73% of visits), medium (22%), and high risk (5%). For MSM at low risk, the six-month probability of increasing risk was 0.11. For MSM at medium risk, the probability of increasing to high risk was 0.08, while the probability of decreasing to low risk was 0.33. For MSM at high risk, the probability of decreasing risk was 0.43. Chemsex, erection stimulants and poppers, high HIV risk perception, and recent STI diagnosis were associated with increased risk at the next visit. High HIV risk perception and young age were associated with decreasing risk. Although the majority of MSM showed no behavior change, a considerable proportion increased HIV risk. Determinants associated with behavior change may help to identify MSM who are likely to increase risk in the near future and target interventions at these individuals, thereby reducing HIV transmission.

Background: Optimising HIV pre-exposure prophylaxis (PrEP) provision requires insight into preferences of PrEP regimens and PrEP discontinuation. We assessed regimen switching and discontinuation and their determinants among men who have sex with men (MSM) participating in the Amsterdam PrEP demonstration project. Methods: Between 3-August-2015 and 31-May-2016, we enrolled MSM (n = 374) and TGP (n = 2) in a prospective, longitudinal study. Participants could choose between daily or event-driven PrEP regimens at enrolment and every 3 months. We assessed transition intensities (TI) and determinants of switching (i) between regimens, and (ii) from either regimen to discontinuing PrEP using a multi-state Markov model. PrEP discontinuation was defined as formally stopping study participation or having no study visit for ≥6 months. Findings: Of 367 analysed participants, 73·3% chose daily and 26·7% event-driven PrEP at enrolment. Median follow-up was 3·1 years (IQR 2·9–3·2). 121 participants switched their PrEP regimen at least once (cumulative probability 34·2%, 95% CI 29·4–39·6), with 90 switches from event-driven to daily PrEP (TI 0·35/PY, 95% CI 0·29–0·44) and 113 switches from daily to event-driven PrEP (TI 0·16/PY, 95% CI 0·13–0·20). Switching from event-driven to daily PrEP was associated with younger age, not reporting sex with HIV-positive partners, chemsex, and sexual compulsivity. Switching from daily to event-driven PrEP were associated with younger age and lower sexual satisfaction. 67 participants discontinued PrEP (cumulative probability 17·7%, 95% CI 14·1–22·2), with no difference between regimens: event-driven (n = 23, TI 0·08/PY, 95% CI 0·05–0·13) and daily PrEP (n = 44, TI 0·06/PY, 95% CI 0·04–0·08). Discontinuing daily PrEP was associated with younger age, fewer casual partners, and higher number of condomless anal sex acts with casual partners. Interpretation: Switching between PrEP regimens was common, while going from event-driven to daily PrEP use was associated with certain sexual-related determinants (i.e. chemsex, sexual compulsivity, no known HIV-positive partners). PrEP discontinuation rates were low and independent of regimens. PrEP care should consider the reasons for choice and switch of regimen and involve education on safely switching or discontinuing PrEP, especially among younger MSM. Funding: ZonMw, H-TEAM, RIVM, GGD research funds, Aidsfonds, Amsterdam Diner Foundation, Gilead Sciences, Gilead Sciences Europe Ltd, Janssen Pharmaceuticals, MAC AIDS Fund, ViiV Healthcare.

To facilitate HCV diagnosis, we developed an HCV-RNA testing service, which involved home-sampled dried blood spots (DBS). The main objective of this study was to evaluate the feasibility of self-sampling at home. Furthermore, to optimise the processing of DBS samples for RNA detection, we evaluated two elution buffers: phosphate-buffered saline (PBS) and L6-buffer. 27 HCV-RNA and 12 HIV-1 RNA positive patients were included. Laboratory spotted DBS (LabDBS) were made by a technician from blood samples drawn at inclusion. Patients received a DBS home-sampling kit and were requested to return their self-sampled DBS (ssDBS) by mail. We compared the RNA load of PBS and L6-eluted labDBS, and of L6-eluted ssDBS, L6-eluted labDBS and plasma. LabDBS load measurements were repeated after 7-13 and 14-21 days to evaluate RNA stability. All 39 plasma samples provided quantifiable RNA loads. In 1/39 labDBS sample, RNA could not be detected (plasma HCV load: 2.98 log10 IU/ml). L6-eluted samples gave a 0.7 log10 and 0.6 log10 higher viral load for HCV and HIV-1 respectively, compared to PBS-eluted samples. Strong correlations were found between labDBS and ssDBS HCV RNA (r = 0.833; mean difference 0.3 log10 IU/mL) and HIV-1 RNA results (r = 0.857; mean difference 0.1 log10 copies/mL). Correlations between labDBS and plasma values were high for HCV (r = 0.958) and HIV-1 (r = 0.844). RNA loads in DBS remained stable over 21 days. Our study demonstrates that self-sampling dried blood spots at home is a feasible strategy for the detection of HCV and HIV-1 RNA. This could facilitate one-step diagnostics and treatment monitoring in communities with high HCV prevalence.

Objectives: To assess the in vitro effect of select antimicrobials on the growth of N. gonorrhoeae and its pharmacodynamic parameters. Methods: Time–kill assays were performed on two reference N. gonorrhoeae strains (ceftriaxone-resistant WHO X and ceftriaxone-susceptible WHO F) and one clinical N. gonorrhoeae strain (ceftriaxone-susceptible CS03307). Time–kill curves were constructed for each strain by measuring bacterial growth rates at doubling antimicrobial concentrations of ceftriaxone, ertapenem, fosfomycin and gentamicin. Inputs from these curves were used to estimate minimal bacterial growth rates at high antimicrobial concentrations (ψmin), maximum bacterial growth rates in the absence of antimicrobials (ψmax), pharmacodynamic minimum inhibitory concentrations (zMIC), and Hill’s coefficients (κ). Results: Ceftriaxone, ertapenem and fosfomycin showed gradual death overtime at higher antimicrobial concentrations with a relatively high ψmin, demonstrating time-dependent activity. Compared to WHO F, the ψmin for WHO X was significantly increased, reflecting decreased killing activity for ceftriaxone, ertapenem and fosfomycin. At high ceftriaxone concentrations, WHO X was still efficiently killed. CS03307 also showed a high ψmin for ceftriaxone in spite of a low MIC and no difference in ψmin for fosfomycin in spite of significant MIC and zMIC differences. Gentamicin showed rapid killing for all three strains at high concentrations, demonstrating concentration-dependent activity. Conclusions: Based on time–kill assays, high-dosage ceftriaxone could be used to treat N. gonorrhoeae strains with MIC above breakpoint, with gentamicin as a potential alternative. Whether ertapenem or fosfomycin would be effective to treat strains with a high MIC to ceftriaxone is questionable.

In individuals infected with hepatitis B virus (HBV), the loss of hepatitis B surface antigen (HBsAg) is the ultimate therapeutic goal, which defines “functional cure.” For individuals living with human immunodeficiency virus (HIV), functional cure occurs roughly 2 per 100 person-years during potent anti-HBV containing antiretroviral therapy. Although this rate may be higher than expected in treated HBV mono-infected individuals, rates of functional cure widely vary between studies (0.6–10.5 per 100 person-years). Similar to HBV mono-infection, the phase of HBV infection, HBV (sub-)genotypes and hepatitis B “e” Ag-negative variants are associated with functional cure in treated HIV-HBV co-infection. In specifically HIV-HBV co-infected individuals, strong increases in CD4+ T cell counts after treatment initiation have also been linked to functional cure, yet this finding is inconsistent across studies. Several markers directly or indirectly reflecting HBV activity are being developed to predict functional cure, such as quantification of HBsAg, hepatitis B core-related antigen, HBsAg protein composition, anti-hepatitis B core antibodies and interferon-gamma-inducible protein 10. Few have been assessed during treatment in HIV-HBV co-infected individuals and none have been validated to predict functional cure. Novel therapeutics for HBV cure are essential for individuals with HIV-HBV co-infection and need to be separately evaluated in this population.

People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infections and are frequently homeless. To improve HCV case finding in these individuals, we examined the feasibility of rapid HCV RNA testing in homeless services in Amsterdam. In 2020, we provided a comprehensive service to homeless facilities, which included workshops on HCV for personnel, a “hepatitis ambassador” at each facility, a rapid, onsite HCV RNA fingerstick test service, and assistance with linkage to care. Risk factors for HCV RNA-positive status were examined using Bayesian logistic regression. Of the 152 participants enrolled, 150 (87% men; median age: 47 years) accepted rapid HCV testing. Seven tested HCV RNA positive (4.7%, 95%CrI = 1.31–8.09; 7/150). Of these, five (71%) were linked to care, of whom four (57%, 4/7) initiated treatment and one (14%, 1/7) delayed treatment due to a drug–drug interaction. Of these four people, two completed treatment (50%), of whom one (25%) achieved sustained virologic response after 12 weeks. HCV RNA-positive individuals were more likely to originate from Eastern Europe (posterior-odds ratio (OR) = 3.59 (95% credible interval (CrI) = 1.27–10.04)) and to inject drugs (ever: posterior-OR = 3.89 (95% CrI = 1.37–11.09); recent: posterior-OR = 3.94 (95% CrI = 1.29–11.71)). We identified HCV RNA-positive individuals and linkage to care was relatively high. Screening in homeless services with rapid testing is feasible and could improve HCV case finding for PWID who do not regularly attend primary care or other harm reduction services for people who use drugs.

Understanding the factors that delineate the efficacy of T cell responses towards pathogens is crucial for our ability to develop potent therapies against infectious diseases. Multidimensional evaluation of T cell functionality at the single-cell level enables exhaustive analysis of combinatorial functional properties, hence polyfunctionality. We have recently invented an algorithm that quantifies polyfunctionality, the Polyfunctionality Index (Larsen et al. PLoS One 2012). Here we demonstrate that quantitative assessment of T cell polyfunctionality correlates with T cell efficacy measured as the capacity to kill target cells in vitro and control infection in vivo.We employed the polyfunctionality index on two datasets selected for their unique ability to evaluate the polyfunctional imprint on T cell efficacy. 1) HIV-specific CD8+ T cells and 2) Leishmania major-specific CD4+ T cells were analysed for their capacity to secrete multiple effector molecules, kill target cells and control infection. Briefly, employing the Polyfunctionality Index algorithm we determined the parameter estimates resulting in optimal correlation between T cell polyfunctionality and T cell efficacy.T cell polyfunctionality is correlated with T cell efficacy measured as 1) target killing (r=0.807, P

BackgroundWhile residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences.MethodsThis cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL ResultsNo significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8-10.9), nadir CD4+T-cell (208/mm3, IQR = 143-378), and CD4+T-cell count (555/mm3, IQR = 458-707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements.ConclusionsHigher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.

BackgroundIn low hepatitis B virus (HBV)-prevalent countries, most HBV-infected persons are unaware of their status. We aimed to evaluate whether (i) previous HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations identified infected individuals and which risk-factor groups needing testing.MethodsDuring a mass, multi-center HBV-screening study from September 2010-August 2011, 3929 participants were screened for hepatitis B surface antigen (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on HBV risk-factors and testing practices were asked to participants, while participants' eligibility for HBV-testing was asked to study medical professionals.Results85 (2.2%) participants were HBsAg-positive, while 659 (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing practices, HBV-testing was more likely to occur in HBV-infected participants if Centers for Disease Control and Prevention (CDC) recommendations were used (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity = 87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3-47.6) (pConclusionsMissed opportunities of HBV-screening are largely due to underestimating country of origin as a risk-factor. Applying CDC-recommendations could improve HBV-screening, but with the disadvantage of many tests. Further development of HBV-testing strategies is necessary, especially before severe disease occurs.

OBJECTIVE: To ascertain patterns of parental smoking in the vicinity of children in Eastern and Western Europe and their relation to Tobacco Control Scale (TCS) scores. METHODS: Data on parental smoking patterns were obtained from the School Child Mental Health Europe (SCMHE), a 2010 cross-sectional survey of 5141 school children aged 6 to 11 years and their parents in six countries: Germany, Netherlands, Lithuania, Romania, Bulgaria and Turkey ranked by TCS into three level categories toward tobacco control policies. RESULTS: A slightly higher proportion of Eastern compared to Western European mothers (42.4 vs. 35.1%) were currently smoking in but the difference was not statistically significant after adjusting for maternal age and maternal educational attainment. About a fifth (19.3%) and a tenth (10.0%) of Eastern and Western European mothers, respectively, smoked in the vicinity of their children, and the difference was significant even after adjustment for potential confounders (p

Increasing numbers of pyelonephritis-associated uropathogenic Escherichia coli (UPEC) are exhibiting high resistance to antibiotic therapy. They include a particular clonal group, the CTX-M-15-producing O25b:H4-ST131 clone, which has been shown to have a high dissemination potential. Here we show that a representative isolate of this E. coli clone, referred to as TN03, has enhanced metabolic capacities, acts as a potent intestine- colonizing strain, and displays the typical features of UPEC strains. In a modified streptomycin-treated mouse model of intestinal colonization where streptomycin was stopped 5 days before inoculation, we show that TN03 outcompetes the commensal E. coli strains K-12 MG1655, IAI1, and ED1a at days 1 and 7. Using an experimental model of ascending UTI in C3H/HeN mice, we then show that TN03 colonized the urinary tract. One week after the transurethral inoculation of the TN03 isolates, the bacterial loads in the bladder and kidneys were significantly greater than those of two other UPEC strains (CFT073 and HT7) belonging to the same B2 phylogenetic group. The differences in bacterial loads did not seem to be directly linked to differences in the inflammatory response, since the intrarenal expression of chemokines and cytokines and the number of polymorphonuclear neutrophils attracted to the site of inflammation was the same in kidneys colonized by TN03, CFT073, or HT7. Lastly, we show that in vitro TN03 has a high maximum growth rate in both complex (Luria-Bertani and human urine) and minimum media. In conclusion, our findings indicate that TN03 is a potent UPEC strain that colonizes the intestinal tract and may persist in the kidneys of infected hosts.