Anders Boyd’s research while affiliated with U.S. Army Medical Research Institute of Infectious Diseases and other places

Objective To assess whether the COVID-19 and mpox outbreaks affected hepatitis C virus (HCV) related behaviours among men who have sex with men (MSM) with a cleared HCV infection. Design Longitudinal analysis from the international ICECREAM trial (2021-2024). Methods During the pre-randomization phase (i.e., without any intervention) individuals completed questionnaires on sexual and drug use behaviours and whether the COVID-19 (since start trial) or mpox (shortly after the mpox outbreak in 2022) outbreaks caused changes in these behaviours, all referring to the preceding six months. We used mixed-effects logistic regression to model changes in behaviours due to COVID-19 or mpox measures and mixed-effects linear regression to model the average HCV-MOSAIC risk score, as a proxy of HCV-associated risk behaviour, over calendar time. Results 220 MSM (n = 117 from the Netherlands, n = 103 from France) were included. Among 208 that completed the baseline questionnaire, 171 (82.2%) were MSM with HIV. The proportion of individuals reporting any impact of COVID-19 restrictions on risk behaviours, mainly lowering number of partners, decreased from 74.7% in September 2021 to 6.7% in September 2024 ( p < 0.001) and reporting any impact of mpox from 41.9% in November 2022 to 6.0% in September 2024 ( p = 0.001). The average HCV-MOSAIC risk score remained constant over time ( p = 0.59) and was consistently ≥2.0, indicating high reinfection susceptibility. Conclusion HCV-related behaviours decreased when COVID-19 and mpox measures were in place. However, individuals still engaged in behaviours associated with HCV, highlighting the importance of continued sexual health services and prevention efforts during such outbreaks.

Objectives Among users of oral HIV pre-exposure prophylaxis (PrEP), condom use is low and incidence of sexually transmitted infections (STIs) is high, hence guidelines recommend STI screening every 3–6 months. Identifying individuals with higher asymptomatic STI risk for targeted screening may offer an opportunity to reduce the burden of STI screening. Methods In the Netherlands, PrEP has been offered through the National PrEP Pilot Program since 2019, which includes screening every 3 months. We included data of all individuals who received care through the PrEP programme between July 2019 and June 2022 and attended at least one PrEP care visit. STI-related symptoms and notification of possible STI exposure by sexual partners are recorded during each visit. We assessed the predictors of any chlamydia, gonorrhoea or syphilis infection diagnosed during routine asymptomatic STI screening (ie, no reported symptoms or partner notification) using logistic regression and calculated risk scores from coefficients of the multivariable logistic regression model. We estimated the sensitivity and specificity for the optimal prediction score cut-off. Results Among the 11 035 included individuals (97% men who have sex with men), 14 926 bacterial STIs (9114 diagnosed during routine asymptomatic screening) were diagnosed during a median of 24 months (IQR 15–30) of follow-up. We found that PrEP users who engaged in sex work, had condomless anal sex, participated in group sex or chemsex (ie, use of gamma-hydroxybutyrate/gamma-butyrolactone, mephedrone or crystallised methamphetamine during sex), injected drugs or used alcohol or non-chemsex-related drugs during sex had an increased risk of STIs diagnosed during routine asymptomatic screening. PrEP users born in the Netherlands and those who attended college or university had a lower STI risk. A risk score using these covariates resulted in a sensitivity of 0.55 (95% CI 0.54 to 0.56) and specificity of 0.55 (95% CI 0.54 to 0.55). Individuals eligible for STI screening accounted for 54% of STIs diagnosed during follow-up. Conclusions Using routinely available demographic and behavioural data, it was not possible to construct a well-performing risk score to identify individuals at high risk of STIs diagnosed during routine asymptomatic screening. Other factors, methods or ways to analyse data may be needed to increase predictive capacity for STI risk scores.

Source and contact tracing (SCT) is a core public health measure that is used to contain the spread of infectious diseases. It aims to identify a source of infection, and to advise those who have been exposed to this source. Due to the rapid increases in incidence of COVID-19 in the Netherlands, the capacity to conduct a full SCT quickly became insufficient. Therefore, the public health services (PHS) might benefit from a restricted strategy targeted to geographical regions where (predicted) case-to-case transmission is high. In this study, we set out to develop a prediction model for the number of COVID-19 cases per postal code within the Netherlands using geographic and demographic features. The study population consists of individuals residing in one of the participating nine Dutch PHS regions who tested positive for SARS-CoV-2 between 1 June 2020 and 27 February 2021. Using a machine learning random forest regression model, we predicted the top 100 postal codes with the highest number of cases with an accuracy of 49% for the current week, 42% for next week, and 44% for two weeks from present. In addition, the age groups of 20-39 and 40-64 years had a higher prediction accuracy than groups outside these age ranges. The developed model provides a starting point for targeted preventive SCT efforts that incorporate geospatial and demographic characteristics of a neighbourhood. It should nonetheless be noted that during the early stages of the outbreak, the number of available datapoints needed to inform such models are likely insufficient. Given the accuracy and data requirements of the developed model, it is unlikely that this class of models can play a pivotal role in informing policy during the early phases of a future epidemic.

Objective People with HIV-HCV co-infection need antiretroviral treatment (ART) to suppress HIV and direct-acting antivirals (DAAs) to cure HCV. ART is typically prioritized, but delays in DAA initiation may increase the risk of liver-related events and HCV transmission to others. Design Target trial emulation with observational data collected in routine clinical practice from a collaboration of cohorts from Europe and North America. Methods We included DAA-naïve adults with HIV-HCV co-infection who achieved HIV virologic suppression (HIV RNA<50 copies/mL) after starting ART between 2013–2020. We 1) estimated the probability of not initiating DAAs at 6 and 36 months after HIV virologic suppression, and 2) emulated a target trial of early (≤6 months after HIV virological suppression) versus delayed (>6 months) DAA initiation and the 36-month risk of liver-related events (liver decompensation or hepatocellular carcinoma). Results Of 862 eligible individuals (median age 46 years; interquartile range 36 to 56), 14% were women, and 52% had a history of injection drug use. The 6 and 36-month probabilities of not initiating DAA were 58% (95% CI: 55, 61) and 24% (21, 27), respectively. The 36-month risk of liver-related events was 1.1% (0.4, 2.0) for early initiation and 1.7% (0.7, 2.5) for delayed initiation; risk difference -0.5% (-1.2, 0.4). Conclusions Almost one-quarter of people with HIV-HCV co-infection on ART had not initiated DAA 3 years after HIV virologic suppression. Because the 3-year risk of liver-related events was low, estimates of the impact of delayed DAA initiation were imprecise.

Purpose Patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) who lack clinical improvement are frequently treated with high-dose corticosteroids (HDS). Since HDS is used to reduce hyperinflammation in these patients, levels of (pro-)inflammatory biomarkers after commencing HDS treatment could be useful in predicting mortality. This study aims to evaluate biomarker levels after commencing HDS over time, along with their capacity to predict mortality. Patients and Methods This retrospective cohort study included patients with COVID-19 ARDS treated with HDS in the intensive care unit (ICU) at an academic hospital in the Netherlands between March 2020-March 2022. Inflammatory biomarkers (ie, C-reactive protein (CRP), D-dimer, ferritin, leukocyte count, interleukin-6 (IL-6), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and procalcitonin (PCT)) were assessed daily from start of HDS (ie baseline) until day 7. Associations between biomarker levels and all-cause-hospital-mortality were evaluated each day using logistic regression, with cut-offs identified by optimizing sensitivity (Se) and specificity (Sp). Results Of the 122 patients included, 53 (43.4%) died during hospitalization. HDS was initiated for a median 7 days (IQR=1–11) after ICU admission. At baseline, a moderately high predictive capacity for mortality was observed at a ferritin level >1281 µg/L (Se=62%/Sp=64%), leukocyte count >13.7 × 109/L (Se=42%/Sp=79%), and NLR >12.1 (Se=61%/Sp=77%). During follow-up, CRP >50 mg/L on day 6 (Se=50%/Sp=75%) and >42 mg/L on day 7 (Se=50%/Sp=75%), ferritin >1082 µg/L on day 6 (Se 63%/Sp=71%) and >1852 µg/L on day 7 (Se=31%/Sp=79%), IL-6 >67 mg/L on day 7 (Se=56%/Sp=79%) and LDH >396U/L on day 6 (Se=38%/Sp=83%) and >373 U/L on day 7 (Se=47%/Sp=72%) showed moderate capacity to predict mortality. NLR was consistently associated with mortality for all days, except day 1 (Se=36–68%/Sp=72-92%). Conclusion In COVID-19 ARDS patients receiving HDS, several clinically available inflammatory biomarkers moderately predicted all-cause-hospital-mortality after the start of HDS, particularly on days 6 and 7. NLR demonstrated the most consistent association with mortality over time. The use of these markers requires validation in larger cohorts.