Weight, anthropometric and metabolic changes after discontinuing antiretroviral therapy containing tenofovir alafenamide (TAF) in people with HIV.

BACKGROUND: Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). While weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. METHODS: We included participants who received at least six months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: TDF-based ART, dolutegravir/lamivudine (DTG/3TC), or long-acting cabotegravir/rilpivirine (CAB/RPV). RESULTS: Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54 kg (95% CI -0.98 to -0.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (CI -2.72 to -0.97), and to a decrease in mean total cholesterol (-0.44 mmol/L) and triglycerides (-0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17 kg, CI -0.82 to 0.48) or long-acting CAB/RPV (-0.64 kg, CI -2.16 to 0.89) did not lead to reductions in weight. CONCLUSIONS: Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within one year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.

Diagnosis and Therapy of Community-Acquired Pneumonia in the Emergency Department: A Retrospective Observational Study and Medical Audit.

BACKGROUND: Despite advances in therapy, community-acquired pneumonia (CAP) is still associated with significant morbidity and mortality. Several studies conducted in different countries have reported suboptimal adherence to the guidelines. However, there are currently no available data on adherence to CAP guidelines specifically in Switzerland. OBJECTIVES: The aim of this study was to audit the quality of diagnosis and therapy of CAP at a Swiss general hospital. METHODS: A retrospective, observational, single-center cohort study was conducted, including patients older than 18 years diagnosed with CAP and admitted to a medical ward throughout 2019 without prior antibiotic therapy prescribed by their general practitioner (GP). The baseline characteristics of the patients were analyzed, and the diagnostic workup and treatment were compared to the Swiss guidelines for CAP. RESULTS: A total of 254 patients diagnosed with CAP were included in this study (median age 78 years, 51.6% males). Atypical pneumonia was diagnosed in 4% of patients, while an organism was identified in 33% of cases, with Streptococcus pneumoniae being the most frequently detected pathogen (57%). A chest image was taken in almost all patients. Documentation of respiratory rate was missing in 23% of cases. Procalcitonin was measured in 23.2% of cases. Pneumococcal and legionella urinary antigen testing was performed on approximately 90% of all patients and blood cultures were drawn in approximately 80% of patients. In 39% of cases, arterial blood gas analysis was performed. Guideline adherence for the administration of empiric antibiotics was documented/recorded in 75% of cases. Twelve different antibiotic regimens were administered, and they were mostly amoxicillin/clavulanate with or without macrolides, as suggested by the guidelines. In particular, the use of ceftriaxone was higher (19.7%) compared to the Swiss guidelines. The average length of antibiotic therapy was longer (8.2 days) compared to the guidelines (5-7 days). Oral steroid therapy was administered to 29.1% of patients, including to 75% of those diagnosed with COPD. CONCLUSION: Overall, guideline adherence was moderately low, especially with regards to the assessment of respiratory rate, performance of arterial blood gas analysis, and sputum collection. Regarding antibiotic therapy, the use of ceftriaxone and the length of antibiotic therapy should be reduced. Further research is needed to identify the reasons for guideline non-adherence, and to find effective measures for the improvement of guideline adherence.

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. METHODS: Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, the model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and nonobese individuals. RESULTS: The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with nonobese (BMI: 18.5-25 kg/m2) individuals, consistent with observed clinical data. Etravirine and rilpivirine were the most impacted, especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load than nonobese PWH. CONCLUSIONS: The concentrations of ARVs are modestly reduced in obese individuals, with no negative impact on the virological response. Our data provide reassurance that standard doses of ARVs are suitable in obese PWH, including those who gained substantial weight with some of the first-line ARVs.

Incidence of sexually transmitted infections and association with behavioural factors: Time-to-event analysis of a large pre-exposure prophylaxis (PrEP) cohort.

OBJECTIVES: Our objective was to obtain long-term data on the incidence of sexually transmitted infections (STIs) and their association with behavioural factors after widespread pre-exposure prophylaxis (PrEP) implementation. METHODS: This was a time-to-event analysis of a national PrEP cohort in Switzerland (SwissPrEPared study). Participants were people without HIV interested in taking PrEP with at least two STI screening visits. Primary outcomes were incidence rate of gonorrhoea, chlamydia, and syphilis. The association between behavioural factors and STI diagnosis was expressed using hazard ratios. We adjusted for testing frequency and calendar year. RESULTS: This analysis included 3907 participants enrolled between April 2019 and April 2022, yielding 3815.7 person-years of follow-up for gonorrhoea (15 134 screenings), 3802.5 for chlamydia (15 141 screenings), and 3858.6 for syphilis (15 001 screenings). The median age was 39 years (interquartile range [IQR] 32-47), 93.8% (n = 3664) identified as men who have sex with men (MSM). The incidence was 22.8 (95% confidence interval [CI] 21.3-24.4) per 100 person-years for gonorrhoea, 26.3 (95% CI 24.7-28.0) for chlamydia, and 4.4 (95% CI 3.8-5.1) for syphilis. Yearly incidence rates decreased between 2019 (all bacterial STIs: 81.6; 95% CI 59.1-109.9) and 2022 (all bacterial STIs: 49.8; 95% CI 44.6-55.3). Participants reporting chemsex substance use were at higher risk of incident STIs, as were those reporting multiple sexual partners. Younger age was associated with a higher risk of gonorrhoea and chlamydia. CONCLUSIONS: Incidence rates of bacterial STIs decreased over time. Young MSM, those with multiple partners, and those using chemsex substances were at increased risk of STIs.

Brief Report: Decreased Physical Activity and Prolonged Sitting Time Are Associated With Liver Steatosis in People With HIV.

BACKGROUND: Physical activity (PA) regulates intrahepatic storage of fat and reduces the risk of liver steatosis. Given our limited understanding of the pathogenesis of metabolic complications in people with HIV (PWH), it remains unclear whether evidence from the general population can be extrapolated to PWH. We investigated the association between PA and liver steatosis in a single site of the Swiss HIV Cohort Study. METHODS: We screened consecutive Swiss HIV Cohort Study participants using vibration-controlled transient elastography and defined liver steatosis as controlled attenuation parameter ≥248 dB/m. PA was measured using the International PA Questionnaire. We evaluated the association of 3 different measures of PA with liver steatosis in separate multivariable logistic regression models. RESULTS: Of 466 participants, 127 (27.3%) were female, median age was 52 years (interquartile range 43-59), and 244 (52.4%) were overweight (body mass index [BMI] ≥25 kg/m 2 ). Liver steatosis was present in 235 (50.4%) individuals. In multivariable analysis, PA below the recommendations of the European Association for the Study of the Liver was associated with steatosis (adjusted odds ratio, 2.34; 95% confidence interval [CI]: 1.44 to 3.85). Using alternative scales of PA, including metabolic equivalents task minutes (min) per week (adjusted odds ratio 0.76, 95% CI: 0.60 to 0.94) and sitting hours per day (aOR, 1.16; 1.07 to 1.26), yielded comparable results, and associations were similar when we restricted the analyses to lean (BMI <25 kg/m 2 ) subjects. CONCLUSIONS: Insufficient PA and prolonged sitting time were associated with liver steatosis among PWH, independent of BMI. Our results support the importance of promoting PA to prevent liver steatosis in PWH.

Pharmacists' approaches to vaccination consultations in Switzerland: a qualitative study comparing the roles of complementary and alternative medicine (CAM) and biomedicine.

BACKGROUND: Many community pharmacies in Switzerland provide complementary and alternative medicine (CAM) approaches in addition to providing biomedical services, and a few pharmacies specialise in CAM. A common perception is that CAM providers are sceptical towards, or opposed to, vaccination. OBJECTIVES: Key objectives of this study are to examine the potential roles of biomedically oriented and CAM-specialised pharmacists regarding vaccine counselling and to better understand the association between vaccine hesitancy and CAM. DESIGN: We conducted semistructured, qualitative interviews. Transcripts were coded and analysed using thematic analysis. Interview questions were related to: type of pharmaceutical care practised, views on CAM and biomedicine, perspectives on vaccination, descriptions of vaccination consultations in community pharmacies and views on vaccination rates. SETTING: Qualitative interviews in three language regions of Switzerland (German, French and Italian). PARTICIPANTS: We interviewed 18 pharmacists (N=11 biomedically oriented, N=7 CAM specialised). RESULTS: Pharmacist participants expressed generally positive attitudes towards vaccination. Biomedically oriented pharmacists mainly advised customers to follow official vaccination recommendations but rarely counselled vaccine-hesitant customers. CAM-specialised pharmacists were not as enthusiastic advocates of the Swiss vaccination recommendations as the biomedically oriented pharmacists we interviewed. Rather, they considered that each customer should receive individualised, nuanced vaccination advice so that customers can reach their own decisions. CAM-specialised pharmacists described how mothers in particular preferred getting a second opinion when they felt insufficiently advised by biomedically oriented paediatricians. CONCLUSIONS: Vaccination counselling in community pharmacies represents an additional option to customers who have unmet vaccination consultation needs and who seek reassurance from healthcare professionals (HCPs) other than physicians. By providing individualised vaccination counselling to vaccine-hesitant customers, CAM-specialised pharmacists are likely meeting specific needs of vaccine-hesitant customers. As such, research and implementation efforts should more systematically involve pharmacists as important actors in vaccination provision. CAM-specialised pharmacists particularly should not be neglected as they are important HCPs who counsel vaccine-hesitant customers.

Impact of Integrase Inhibitors on Cardiovascular Disease Events in People With Human Immunodeficiency Virus Starting Antiretroviral Therapy.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias. METHODS: We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights. RESULTS: Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4-7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval [CI], .46-1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were -0.17% (95% CI, -.37 to .19) after 1 year, -0.61% (-1.54 to 0.22) after 5 years, and -0.71% (-2.16 to 0.94) after 8 years. CONCLUSIONS: In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.

Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years.

BACKGROUND: Accelerated epigenetic ageing can occur in untreated HIV infection and is partially reversible with effective antiretroviral therapy (ART). We aimed to make a long-term comparison of epigenetic ageing dynamics in people with HIV during untreated HIV infection and during suppressive ART. METHODS: In this longitudinal study, conducted over 17 years in HIV outpatient clinics in Switzerland, we applied 5 established epigenetic age estimators (epigenetic clocks) in peripheral blood mononuclear cells (PBMCs) in Swiss HIV Cohort Study participants before or during suppressive ART. All participants had a longitudinal set of PBMC samples available at four timepoints (T1-T4). T1 and T2 had to be 3 years or longer apart, as did T3 and T4. We assessed epigenetic age acceleration (EAA) and a novel rate of epigenetic ageing. FINDINGS: Between March 13, 1990, and Jan 18, 2018, we recruited 81 people with HIV from the Swiss HIV Cohort Study. We excluded one participant because a sample did not meet quality checks (transmission error). 52 (65%) of 80 patients were men, 76 (95%) were white, and the median patient age was 43 (IQR 37·5-47) years. Per year of untreated HIV infection (median observation 8·08 years, IQR 4·83-11·09), mean EAA was 0·47 years (95% CI 0·37 to 0·57) for Horvath's clock, 0·43 years (0·3 to 0·57) for Hannum's clock, 0·36 years (0·27 to 0·44) for SkinBlood clock, and 0·69 years (0·51 to 0·86) for PhenoAge. Per year of suppressive ART (median observation 9·8 years, IQR 7·2-11), mean EAA was -0·35 years (95% CI -0·44 to -0·27) for Horvath's clock, -0·39 years (-0·50 to -0·27) for Hannum's clock, -0·26 years (-0·33 to -0·18) for SkinBlood clock, and -0·49 years (-0·64 to -0·35) for PhenoAge. Our findings indicate that people with HIV epigenetically aged by a mean of 1·47 years for Horvath's clock, 1·43 years for Hannum's clock, 1·36 years for SkinBlood clock, and 1·69 years for PhenoAge per year of untreated HIV infection; and 0·65 years for Horvath's clock, 0·61 years for Hannum's clock, 0·74 years for SkinBlood clock, and 0·51 years for PhenoAge, per year of suppressive ART. GrimAge showed some change in the mean EAA during untreated HIV infection (0·10 years, 0·02 to 0·19) and suppressive ART (-0·05 years, -0·12 to 0·02). We obtained very similar results using the rate of epigenetic ageing. Contribution of multiple HIV-related, antiretroviral, and immunological variables, and of a DNA methylation-associated polygenic risk score to EAA was small. INTERPRETATION: In a longitudinal study over more than 17 years, epigenetic ageing accelerated during untreated HIV infection and decelerated during suppressive ART, highlighting the importance of limiting the duration of untreated HIV infection. FUNDING: Swiss HIV Cohort Study, Swiss National Science Foundation, and Gilead Sciences.

Association of a Polygenic Risk Score With Osteoporosis in People Living With HIV: The Swiss HIV Cohort Study.

BACKGROUND: Bone mineral density (BMD) loss may be accelerated in people with HIV (PLWH). It is unknown whether a polygenic risk score (PRS) is associated with low BMD in PLWH. METHODS: Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011-2020). Univariable and multivariable odds ratios (ORs) for DXA-defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9413 single-nucleotide polymorphisms associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. RESULTS: We included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34-9.67) and 4.13 (1.86-9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37-3.74), 1.84 (1.40-2.43), and 1.54 (0.82-2.9). CONCLUSIONS: In PLWH in Switzerland, osteoporosis was independently associated with a BMD-associated PRS after adjustment for established risk factors, including exposure to tenofovir disoproxil fumarate.

Leukocyte Count and Coronary Artery Disease Events in People With Human Immunodeficiency Virus: A Longitudinal Study.

BACKGROUND: People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. RESULTS: We included 536 cases with a first CAD event (2000-2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300-7995] vs 5900 [4910-7200]; P < .01), but leukocytosis (>11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events. CONCLUSIONS: PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.

Brief Report: Does Menopause Transition Influence Viral Suppression and Adherence in Women Living With HIV?

BACKGROUND: Increasing numbers of women living with HIV transition through menopause. It is unclear whether this transition has an impact on treatment adherence, viral suppression, psychiatric comorbidities, or drug use. We aimed at examining adherence and viral suppression during the perimenopausal period and explored the influence of psychiatric comorbidities and active injection drug use (IDU). SETTING: Retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. METHODS: We explored perimenopausal and postmenopausal trends of viral blips, low-level viremia, viral failure, adherence, psychiatric comorbidities, and IDU using interrupted time series models. RESULTS: Rates of depression and psychiatric care increased during perimenopause before decreasing afterward. Negative treatment outcomes such as viral blips, low-level viremia, viral failure, and low adherence steadily declined while transitioning through menopause-this was also true for subgroups of women with depression, psychiatric treatment, and active IDU. CONCLUSIONS: Increased rates of depression and psychiatric care while transitioning through menopause do not result in lower rates of adherence or viral suppression in women living with HIV in Switzerland.

Polygenic Risk Scores for Prediction of Subclinical Coronary Artery Disease in Persons With Human Immunodeficiency Virus (HIV): The Swiss HIV Cohort Study.

BACKGROUND: In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical CAD is unknown. METHODS: In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population. RESULTS: We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval [CI], 1.18-5.67), and a CAC OR = 3.95 (95% CI, 1.45-10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75-59.11), and a CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively). CONCLUSIONS: In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.

Health Care Professionals' Interest in Vaccination Training in Switzerland: A Quantitative Survey.

Objectives: Health care professionals (HCPs) play an important role for patients' vaccination decisions. To counsel patients/clients appropriately, HCPs need current factual knowledge about vaccines and strong communication skills. Methods: We conducted an online survey with physicians, pharmacists, nurses, and midwives in Switzerland (01.11.2020-31.03.2021). We evaluated: 1) interest in vaccination knowledge and counseling training; 2) vaccination recommendation practices; 3) experience with vaccination counseling/administration; 4) comfort level in addressing vaccine hesitancy (VH); 5) perspectives on patient/client VH, delays, and refusals. Results: In total, 1,933 practicing HCPs responded (496 physicians, 226 pharmacists, 607 nurses, 604 midwives). 43% physicians, 31% pharmacists, 15% nurses, and 23% midwives felt comfortable counseling VH patients/clients. 96% physicians, 98% pharmacists, 85% nurses, and 91% midwives were interested in additional vaccination-related training. All professionals mentioned safety, efficacy, and side effects as topics of most interest for additional training. Conclusion: Results demonstrate a high interest among HCPs for additional vaccination-related training. In addition to factual information about vaccination, such training will likely benefit from a communication component, given the low rates of comfort reported by HCPs when counseling VH patients/clients.

Factors Associated With Liver Steatosis in People With Human Immunodeficiency Virus on Contemporary Antiretroviral Therapy.

Background: Given the impact of new antiretroviral drugs on weight and metabolic parameters, their potential contribution to the development of liver steatosis is of concern. We investigated the determinants of liver steatosis in patients on antiretroviral therapy (ART) in the Swiss HIV Cohort Study (SHCS). Methods: Between 2019 and 2021, we measured liver stiffness and controlled attenuation parameter (CAP) using transient elastography in consecutive SHCS participants at Bern University Hospital. Individuals with viral hepatitis coinfection and pregnant women were excluded. We used multivariable logistic regression to explore factors associated with steatosis. Results: Of 416 participants, 113 (27.2%) were female, median age was 51 years (interquartile range [IQR], 43-59), 305 (73.3%) were of European origin, and 212 (51.0%) were overweight/obese (body mass index [BMI] ≥25 kg/m2). Liver steatosis (CAP ≥248 dB/m) was present in 212 (51.0%) participants, 11 (5.2%) of whom had significant fibrosis or cirrhosis. One hundred seventy-nine (43.0%) met the criteria for metabolic-associated fatty liver disease (MAFLD). Among 64 individuals with a BMI <25 kg/m2 and liver steatosis, 31 (48.4%) had MAFLD. In multivariable analyses, BMI ≥25 kg/m2 (adjusted odds ratio, 5.76; 95% confidence interval, 3.57-9.29), age ≥50 years (1.88, 1.14-3.09), European origin (3.16, 1.69-5.89), and current use of tenofovir alafenamide (1.70, 1.08-2.69) were associated with liver steatosis. Exposure to integrase inhibitors was not associated with liver steatosis (0.83, 0.51-1.37). Conclusions: Our findings suggest a high prevalence of liver steatosis among people with HIV (PWH) on ART in Switzerland. In addition to established risk factors, the use of tenofovir alafenamide was associated with hepatic steatosis.

Anticholinergic and Sedative Medications Are Associated With Neurocognitive Performance of Well Treated People With Human Immunodeficiency Virus.

Background: We previously showed that anticholinergic (ACH) medications contribute to self-reported neurocognitive impairment (NCI) in elderly people with human immunodeficiency virus (PWH). The current cross-sectional study further evaluated the effect of ACH and sedative drugs on neurocognitive function in PWH who underwent comprehensive neuropsychological evaluation. Methods: A medication review was performed in PWH enrolled in the prospective Neurocognitive Assessment in Metabolic and Aging Cohort within the Swiss HIV Cohort Study. Neurocognitive functions were analyzed in 5 domains (motor skills, speed of information, attention/working memory, executive functions, and verbal learning memory). The effect of ACH and sedative medications on neurocognitive functioning was evaluated using linear regression models for the continuous (mean z-score) outcome and multivariable logistic regression models for the binary (presence/absence) outcome. Results: A total of 963 PWH (80% male, 92% Caucasian, 96% virologically suppressed, median age 52) were included. Fourteen percent of participants were prescribed ≥1 ACH medication and 9% were prescribed ≥1 sedative medication. Overall, 40% of participants had NCI. Sedative medication use was associated with impaired attention/verbal learning and ACH medication use with motor skills deficits both in the continuous (mean z-score difference -0.26 to -0.14, P < .001 and P = .06) and binary (odds ratio [OR], ≥1.67; P < .05) models. Their combined use was associated with deficits in overall neurocognitive functions in both models (mean z-score difference -0.12, P = .002 and OR = 1.54, P = .03). These associations were unchanged in a subgroup analysis of participants without depression (n = 824). Conclusions: Anticholinergic and sedative medications contribute to NCI. Clinicians need to consider these drugs when assessing NCI in PWH.

Vaccine hesitancy and HPV vaccine uptake among male and female youth in Switzerland: a cross-sectional study.

OBJECTIVES: Identifying factors associated with human papillomavirus (HPV) vaccine uptake is essential for designing successful vaccination programmes. We aimed to examine the association between vaccine hesitancy (VH) and HPV vaccine uptake among male and female youth in Switzerland. DESIGN: With a cross-sectional study, an interview-based questionnaire was used to collect information on sociodemographic factors, vaccination records and to measure the prevalence of VH using the Youth Attitudes about Vaccines scale (YAV-5), a modified version of the Parent Attitudes about Childhood Vaccinations survey instrument. SETTING AND PARTICIPANTS: Eligible male and female participants, 15-26 years of age, were recruited through physicians' offices and military enlistment in all three language regions of Switzerland. Of 1001 participants, we included 674 participants with a vaccination record available (415 males and 259 females) in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome was uptake for HPV vaccine (having received ≥1 dose of HPV vaccine). Covariates were VH, sex, age and other sociodemographics. RESULTS: 151 (58%) female and 64 (15%) male participants received ≥1 dose of HPV vaccine. 81 (31%) female and 92 (22%) male participants were VH (YAV-5-Score >50). The odds for being unvaccinated were higher for VH women than non-VH women, adjusted OR=4.90 (95% CI 2.53 to 9.50), but similar among VH and non-VH men, OR=1.90 (95% CI 0.84 to 4.31). The odds for being unvaccinated were lower for younger men (born on or after 1 July 2002) than older men (born before 1 July 2002), OR=0.34 (95% CI 0.14 to 0.81), but we found no association between age and vaccine uptake for female youth, OR=0.97 (95% CI 0.48 to 1.97). CONCLUSIONS: VH was associated with lower HPV vaccine uptake in female youth but not male youth in our study population in Switzerland. Our findings suggest that issues other than VH contribute to HPV underimmunisation in male youth in Switzerland.

Parental and provider vaccine hesitancy and non-timely childhood vaccination in Switzerland.

OBJECTIVE: Although medical providers are a trusted vaccination information source for parents, they do not universally support vaccination. Complementary medicine (CM) providers are particularly likely to hold vaccine hesitant (VH) views, and VH parents often consult with them. Little research compares VH of parents and providers, and if and how each is associated with uptake of recommended childhood vaccines. METHODS: We defined non-timely receipt as recommended vaccines given > 1 month later than officially recommended, based on vaccination records. We administered versions of the Parent Attitudes about Childhood Vaccines (PACV) 5-item survey instrument to 1256 parents and their children's pediatricians (N = 112, 40 CM-oriented, 72 biomedical [not CM-oriented]) to identify moderately (PACV-score 5-6) and highly (PACV-score 7+) hesitant providers/parents. We obtained multivariable adjusted odds ratios to test relationships between parental VH and provider type/VH, and between non-timely receipt of selected childhood vaccines and parental VH and provider type/VH. RESULTS: No biomedical providers were VH, 9 CM providers were moderately VH, and 17 were highly VH. Parents seeing moderately and highly hesitant providers had adjusted odds ratio (AOR) for being VH = 6.6 (95% confidence interval (CI), 3.1-14.0) and AOR = 31.3 (95% CI 16.8-58.3), respectively. Across all vaccine uptake endpoints, children of moderately and highly hesitant parents had 1.9-3.8 and 7.1-12.3 higher odds of non-timely vaccination, and children seeing highly hesitant CM providers had 4.9-9.4 higher odds. Children seeing moderately hesitant CM providers had 3.3 higher odds of non-timely vaccination for the 1st dose of measles and 3.5 higher odds for 1st dose of polio/pertussis/tetanus. CONCLUSION: VH by both parents and providers each is associated with non-timely childhood vaccination. As VH parents are more likely to consult with VH providers, interventions aimed at increasing timely vaccination need to primarily target VH providers and their clients.

Parents' vaccination information seeking, satisfaction with and trust in medical providers in Switzerland: a mixed-methods study.

OBJECTIVES: The aim of this study was to better understand parental trust in and satisfaction with information sources and medical providers regarding decision making about childhood vaccines. SETTING: The study was part of a Swiss national research programme investigating vaccine hesitancy and underimmunisation. PARTICIPANTS: We conducted qualitative interviews with 37 providers and 30 parents, observed 34 vaccination consultations, and then conducted quantitative surveys with 130 providers (both complementary and alternative medicine (CAM) oriented and biomedically oriented) and 1390 parents. MAIN OUTCOME MEASURES: Participants' vaccination information sources used in their decision-making process, parents' trust in and satisfaction with these sources and providers. RESULTS: Based on the Parent Attitudes about Childhood Vaccines scale, we considered 501 parents as vaccine-hesitant (VH) and 889 parents as non-VH. Whereas both groups mentioned providers as the most trusted source of information, VH-parents were less likely to mention paediatricians (N=358 (71%) vs N=755 (85%)) and public health authorities (N=101 (20%) vs N=333 (37%)) than non-VH-parents. VH-parents were more likely to have consulted another provider (N=196 (39%) vs N=173 (19%)) than non-VH-parents, to express less satisfaction with both their primary (N=342 (82%) vs N=586 (91%)) and other providers (N=82 (42%) vs N=142 (82%)) and less trust in their primary (N=368 (88%) vs N=632 (98%)) and other providers (N=108 (55%) vs N=146 (84%)). VH-parents were less likely to be satisfied with their biomedical primary provider than non-VH-parents (100 (69%) vs 467 (91%)). However, when the primary provider was CAM-oriented, there were similar levels of satisfaction among both groups (237 (89%) VH-parents vs 118 (89%) non-VH-parents). All differences were significant (p<0.05). CONCLUSIONS: While the provider remains the main information source, VH parents turn to additional sources and providers, which is likely related to VH parents being rather dissatisfied with and distrusting in obtained information and their provider. ETHICS: The local ethics committee (Ethikkommission Nordwest- und Zentralschweiz, EKNZ; project ID number 2017-00725) approved the study.

Women with HIV transitioning through menopause: Insights from the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland. METHODS: This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause. RESULTS: Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation. CONCLUSIONS: The median age of women living with HIV at menopause is around 2 years lower than that reported for HIV-negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause-associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy.

HPV vaccine awareness, knowledge and information sources among youth in Switzerland: a mixed methods study.

OBJECTIVES: We aimed to provide a detailed characterisation of human papillomavirus (HPV) vaccine awareness, knowledge and information sources in the HPV vaccine decision-making process of youth, both male and female, in Switzerland. DESIGN: With a mixed-method study design, we conducted quantitative questionnaires and qualitative interviews, which lasted 20-45 min. SETTING AND PARTICIPANTS: We recruited participants, 15-26 years of age, in physicians' offices, in a local sexual health clinic, and during military enlistment. We administered quantitative questionnaires to 997 youth participants (585 male, 412 female) and conducted qualitative interviews with 31 youth (17 male, 14 female). PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed HPV vaccine awareness, knowledge, information sources and vaccination status. RESULTS: In the study's quantitative component, 108 (20%) male and 262 (65%) female participants had received ≥1 dose of HPV vaccine. 697 (70%) participants were knowledgeable about the HPV vaccine. Females were more likely to be knowledgeable than males (342/412 (83%) vs 355/585 (61%); p<0.01). Younger participants in the sample compared with older participants were more likely to be aware of HPV vaccine (135/148 (91%) vs 695/849 (82%); p<0.01). The three most mentioned information sources were school health programmes (442 (53%)), healthcare providers (190 (23%)) and participants' social networks (163 (20%)). Overall, 554/710 (78%) participants had a female-gendered perception of HPV vaccine, a finding which was further supported and explained by qualitative data. CONCLUSIONS: Despite a male HPV vaccine recommendation being made >4 years prior to the data collection, HPV vaccine knowledge was higher among females than males, and a female-gendered perception of HPV vaccine remains prevalent. Internet and social media were minor HPV vaccine information sources. Study findings demonstrate that HPV knowledge matters for HPV vaccine uptake and suggest that we should improve HPV information quality and access for youth, particularly by tailoring knowledge campaigns to young men.