Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure.

Background: The World Health Organization is pushing to accelerate the study of new human immunodeficiency virus drugs in pregnant women. However, regulatory guidelines do not specify when to conduct pharmacokinetic studies in postpartum women. This knowledge gap carries the potential to jeopardize the outcomes and conclusions of clinical trials aiming to study the effect of pregnancy on drug exposure.

Secondary attack rate following on-site isolation of patients with suspected COVID-19 in multiple-bed rooms.

The implementation of isolation precautions for patients with suspected Coronavirus Disease 2019 (COVID-19) and pending test results is resource intensive. Due to the limited availability of single-bed rooms at our institution, we isolated patients with suspected COVID-19 together with patients without suspected COVID-19 on-site in multiple-bed rooms until SARS-CoV-2-test results were available. We evaluated the likelihood of SARS-CoV-2 transmission to individuals sharing the room with patients isolated on-site.

Impact of shift work and other work-related factors on anti-SARS-CoV-2 spike-protein serum concentrations in healthcare workers after primary mRNA vaccination - a retrospective cohort study.

Background: Knowing whether shift work negatively affects the immune system's response to COVID-19 vaccinations could be valuable for planning future vaccination campaigns for healthcare workers. We aimed to determine the impact of working late or night shifts on serum anti-SARS-CoV-2 spike protein immunoglobulin G (anti-S) antibody levels after primary SARS-CoV-2-mRNA vaccination.

Methods: To obtain detailed information on shift work, we sent a separate online questionnaire to 1475 eligible healthcare workers who participated in a prospective longitudinal study conducted in 15 healthcare institutions in Switzerland.

Drug Exposure of Long-Acting Cabotegravir and Rilpivirine in Older People With Human Immunodeficiency Virus: A Pharmacokinetic Modeling Study.

Background: The life expectancy of people with human immunodeficiency virus (PWH) has significantly increased, thanks to combined antiretrovirals with improved potency and tolerability. One further step has been achieved with the development of long-acting (LA) injectable antiretrovirals, which allow for infrequent dosing. However, the pharmacokinetics of LA antiretrovirals has been poorly characterized in older PWH, as they are generally excluded from trials.

Development of a physiologically-based pharmacokinetic model to simulate the pharmacokinetics of intramuscular antiretroviral drugs.

There is growing interest in the use of long-acting (LA) injectable drugs to improve treatment adherence. However, their long elimination half-life complicates the conduct of clinical trials. Physiologically-based pharmacokinetic (PBPK) modeling is a mathematical tool that allows to simulate unknown clinical scenarios for LA formulations.

[Prevalence of menorrhagia among women in Reunion Island].

Objectives: To estimate the prevalence of menorrhagia in women in Reunion Island using the Higham score, to evaluate self-reporting as an alternative diagnostic method, and to study women's level of knowledge about menorrhagia and its impact on their quality of life.

Methods: This was a descriptive, cross-sectional observational study involving 185 adult women with menstrual periods living in Reunion Island. Women volunteered to answer an online self-questionnaire proposed by healthcare professionals from January to May 2023 in Reunion Island.

Effect of Obesity on the Exposure of Long-acting Cabotegravir and Rilpivirine: A Modeling Study.

Background: Obesity is increasingly prevalent among people with human immunodeficiency virus (HIV, PWH). Obesity can reduce drug exposure; however, limited data are available for long-acting (LA) antiretrovirals. We performed in silico trials using physiologically based pharmacokinetic (PBPK) modeling to determine the effect of obesity on the exposure of LA cabotegravir and rilpivirine after the initial injection and after multiple injections.

Deciphering Factors Linked With Reduced Severe Acute Respiratory Syndrome Coronavirus 2 Susceptibility in the Swiss HIV Cohort Study.

Background: Factors influencing susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain to be resolved. Using data from the Swiss HIV Cohort Study on 6270 people with human immunodeficiency virus (HIV) and serologic assessment for SARS-CoV-2 and circulating human coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection.

Methods: We analyzed SARS-CoV-2 polymerase chain reaction test results, COVID-19-related hospitalizations, and deaths reported to the Swiss HIV Cohort Study between 1 January 2020 and 31 December 2021.

Within-host genetic diversity of extended-spectrum beta-lactamase-producing Enterobacterales in long-term colonized patients.

Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records.

Body mass index trends and its impact of under and overweight on outcome among PLHIV on antiretroviral treatment in rural Tanzania: A prospective cohort study.

Introduction: Increased body weight is an important risk factor for cardiovascular disease and is increasingly reported as a health problem in people living with HIV (PLHIV). There is limited data from rural sub-Saharan Africa, where malnutrition usually presents with both over- and undernutrition. We aimed to determine the prevalence and risk factors of underweight and overweight/obesity in PLHIV enrolled in a cohort in rural Tanzania before the introduction of integrase inhibitors.

Antiretroviral Drug Exposure and Response in Obese and Morbidly Obese People With Human Immunodeficiency Virus (HIV): A Study Combining Modelling and Swiss HIV Cohort Data.

Background: Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals.

Evaluation of the clinical relevance of the Biofire FilmArray pneumonia panel among hospitalized patients.

Purpose: Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples.

Intramuscular cabotegravir and rilpivirine concentrations after switching from efavirenz-containing regimen.

Aims: Intramuscular cabotegravir/rilpivirine (IM CAB/RPV) are metabolized by UGT1A1/CYP3A4. Efavirenz induces both enzymes; therefore, switching from an efavirenz-containing regimen to IM CAB/RPV could possibly result in suboptimal levels. Due to their long dosing interval, clinical studies with IM CAB/RPV are challenging.

Impact of Obesity on the Drug-Drug Interaction Between Dolutegravir and Rifampicin or Any Other Strong Inducers.

Background: Obesity is increasingly prevalent among people with HIV. Obesity can impact drug pharmacokinetics and consequently the magnitude of drug-drug interactions (DDIs) and, thus, the related recommendations for dose adjustment. Virtual clinical DDI studies were conducted using physiologically based pharmacokinetic (PBPK) modeling to compare the magnitude of the DDI between dolutegravir and rifampicin in nonobese, obese, and morbidly obese individuals.

Sex-specific differences in myocardial injury incidence after COVID-19 mRNA-1273 booster vaccination.

Aims: To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination.

Methods And Results: Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified.

Management of Drug Interactions with Inducers: Onset and Disappearance of Induction on Cytochrome P450 3A4 and Uridine Diphosphate Glucuronosyltransferase 1A1 Substrates.

Background: People living with HIV may present co-morbidities requiring the initiation and subsequently the discontinuation of medications with inducing properties. The time to reach maximal enzyme induction and to return to baseline enzyme levels has not been thoroughly characterized.

Objective: The aim of this study was to evaluate the onset and disappearance of dolutegravir [uridine diphosphate glucuronosyltransferase (UGT) 1A1 and cytochrome P450 (CYP) 3A4 substrate] and raltegravir (UGT1A1 substrate) induction with strong and moderate inducers using physiologically based pharmacokinetic (PBPK) modeling.

Switch from a ritonavir to a cobicistat containing antiretroviral regimen and impact on tacrolimus levels in a kidney transplant recipient.

Background: Solid-organ transplantation due to end-stage organ disease is increasingly performed in people living with HIV. Despite improved transplant outcomes, management of these patients remains challenging due to higher risk for allograft rejection, infection and drug-drug interactions (DDIs). Complex regimens for multi-drug resistant HIV-viruses may cause DDIs particularly if the regimen contains drugs such as ritonavir or cobicistat.

A qualitative study on the perception of infection prevention and control measures among healthcare workers without patient contact during the SARS-CoV-2 pandemic.

We conducted a qualitative interview-based study to examine the perception of infection prevention and control (IPC) measures implemented during the COVID-19 pandemic among healthcare workers (HCWs) without patient contact in a tertiary academic care center. We compared these findings to those derived from interviews of HCWs with patient contact from the same institution using the same study design. The following main four themes were identified: (1) As for HCWs with patient contact, transparent communication strongly contributes to employees' sense of security.

Effect of SLCO1B1 c.521T>C polymorphism on the lipid response to statins in people living with HIV on a boosted protease inhibitor-containing regimen.

Aims: We previously observed that some individuals on HIV boosted protease inhibitor-containing regimen do not achieve their lipid targets despite elevated statin concentrations. This study evaluated whether the common single polymorphism c.521T>C in SLCO1B1, associated with reduced statin uptake in the liver, could explain this observation.

A systematic outbreak investigation of SARS-CoV-2 transmission clusters in a tertiary academic care center.

Background: We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020.

Methods: At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission.

Physiologically Based Pharmacokinetic Modelling to Identify Physiological and Drug Parameters Driving Pharmacokinetics in Obese Individuals.

Background: Obese individuals are often underrepresented in clinical trials, leading to a lack of dosing guidance.

Objective: This study aimed to investigate which physiological parameters and drug properties determine drug disposition changes in obese using our physiologically based pharmacokinetic (PBPK) framework, informed with obese population characteristics.

Methods: Simulations were performed for ten drugs with clinical data in obese (i.

Persistent High Burden and Mortality Associated With Advanced HIV Disease in Rural Tanzania Despite Uptake of World Health Organization "Test and Treat" Guidelines.

Background: Information about burden, characteristics, predictors, and outcomes of advanced human immunodeficiency virus disease (AHD) is scarce in rural settings of sub-Saharan Africa. Human immunodeficiency virus (HIV) infections and associated deaths remain high despite specific guidelines issued by the World Health Organization (WHO).

Methods: Burden of AHD and 6-month death/loss to follow-up (LTFU) were described among 2498 antiretroviral therapy (ART)-naive nonpregnant people with HIV (PWH) aged >15 years enrolled in the Kilombero Ulanga Antiretroviral Cohort in rural Tanzania between 2013 and 2019.

Quantifying and Predicting Ongoing Human Immunodeficiency Virus Type 1 Transmission Dynamics in Switzerland Using a Distance-Based Clustering Approach.

Background: Despite effective prevention approaches, ongoing human immunodeficiency virus 1 (HIV-1) transmission remains a public health concern indicating a need for identifying its drivers.

Methods: We combined a network-based clustering method using evolutionary distances between viral sequences with statistical learning approaches to investigate the dynamics of HIV transmission in the Swiss HIV Cohort Study and to predict the drivers of ongoing transmission.

Results: We found that only a minority of clusters and patients acquired links to new infections between 2007 and 2020.