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Objectives: We previously demonstrated an association between tenofovir disoproxil fumarate (TDF) and chronic liver enzyme elevation in the D:A:D study. The objective of the study was to assess changes in alanine aminotransferase (ALT) levels after switching from TDF to tenofovir alafenamide (TAF). Methods: We included Swiss HIV Cohort Study participants who switched from TDF to TAF with two or more ALT values in the 24 months before and two or more values in the 24 months after replacing TDF with TAF. Individuals with replicating viral hepatitis were excluded. Uni‐ and multivariable linear mixed models were used to explore changes in ALT values associated with switching from TDF to TAF, and to assess potential modifying effects. Results: A total of 1712 participants were included, contributing 6169 ALT values before and 5482 after switching. Median (interquartile range, IQR) age was 50 (42–57) years, and 75% were male. Median (IQR) ALT was 28 (22–38) U/L before and 24 (19–32) U/L after replacing TDF with TAF. ALT values decreased by 3.7 U/L (95% confidence interval: 3.2–4.2) after the switch. The median drop was larger in patients with chronic ALT elevation (defined as two or more elevated values for ≥ 6 months) compared with patients with normal ALT values (17.8 vs. 3.3 U/L, P < 0.001). We did not identify any major effect modifications of the ALT change with any of the potential variables studied. Conclusions: Replacing TDF with TAF in HIV‐monoinfected people led to a significant decrease in ALT values. Findings were not significantly affected by known risk factors for hepatotoxicity. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosing neurocognitive impairment (NCI) in HIV infection requires time‐consuming neuropsychological assessment. Screening tools are needed to identify when neuropsychological referral is indicated. We examined the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying NCI. Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study recruited patients aged ≥45 years enrolled in the Swiss HIV Cohort Study between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self‐report forms [Center for Epidemiologic Studies Depression Scale (CES‐D)] rating mood. NCI categories were defined using Frascati criteria. PPVs and NPVs of the EACS screening questions in identifying NCI categories were calculated. Results: Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV‐associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV‐associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001). Conclusions: The EACS screening questions had an NPV of 0.7 for excluding patients with HIV‐associated NCI as defined by Frascati criteria. The PPV and NPV may improve if NCI diagnoses are based on new criteria. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. Methods: The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV‐associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z‐score means) were performed. Results: Most patients (942; 96.2%) had viral loads < 50 HIV‐1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV‐associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non‐Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. Conclusions: In this large sample of aging people living with HIV with well‐controlled infection in Switzerland, baseline HIV‐associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course. [ABSTRACT FROM AUTHOR]

Objectives: Late presentation (LP) to HIV care disproportionally affects individuals from sub‐Saharan Africa (SSA). We explored the reasons for late presentation to care among this group of patients in the Swiss HIV Cohort Study. Methods: The prevalence of LP was compared between patients from Western Europe (WE) and those from SSA enrolled between 2009 and 2012. Patients were asked about HIV testing, including access to testing and reasons for deferring it, during face‐to‐face interviews. Results: The proportion of LP was 45.8% (435/950) among patients from WE, and 64.6% (126/195) among those from SSA (P < 0.001). Women from WE were slightly more likely to present late than men (52.6% versus 44.5%, respectively; P = 0.06), whereas there was no sex difference in patients from SSA (65.6% versus 63.2%, respectively; P = 0.73). Compared with late presenters from WE, those from SSA were more likely to be diagnosed during pregnancy (9.1% versus 0%, respectively; P < 0.001), but less likely to be tested by general practitioners (25.0% versus 44.6%, respectively; P = 0.001). Late presenters from SSA more frequently reported 'not knowing about anonymous testing possibilities' (46.4% versus 27.3%, respectively; P = 0.04) and 'fear about negative reaction in relatives' (39.3% versus 21.7%, respectively; P = 0.05) as reasons for late testing. Fear of being expelled from Switzerland was reported by 26.1% of late presenters from SSA. Conclusions: The majority of patients from SSA were late presenters, independent of sex or education level. Difficulties in accessing testing facilities, lack of knowledge about HIV testing and fear‐related issues are important drivers for LP in this population. [ABSTRACT FROM AUTHOR]

The potential for mitochondrial (mt) DNA mutation accumulation during antiretroviral therapy (ART), and preferential accumulation in patients with lipoatrophy compared with control participants, remains controversial. We sequenced the entire mitochondrial genome, both before ART and after ART exposure, in 29 human immunodeficiency virus (HIV)-infected Swiss HIV Cohort Study participants initiating a first-line thymidine analogue-containing ART regimen. No accumulation of mtDNA mutations or deletions was detected in 13 participants who developed lipoatrophy or in 16 control participants after significant and comparable ART exposure (median duration, 3.3 and 3.7 years, respectively). In HIV-infected persons, the development of lipoatrophy is unlikely to be associated with accumulation of mtDNA mutations detectable in peripheral blood. [ABSTRACT FROM AUTHOR]

Background and Objectives Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS). Methods In the SHCS, patients are followed twice a year and scored by the treating physician as having ‘fat accumulation’, ‘fat loss’, or neither. Treatments, and reasons for change thereof, are recorded. Our study sample included all patients treated with cART between 2003 and 2006 and, in addition, all patients who started cART between 2000 and 2003. Results From 2003 to 2006, the percentage of patients taking stavudine, didanosine and nelfinavir decreased, the percentage taking lopinavir, nevirapine and efavirenz remained stable, and the percentage taking atazanavir and tenofovir increased by 18.7 and 22.2%, respectively. In life-table Kaplan–Meier analysis, patients starting cART in 2003–2006 were less likely to develop LD than those starting cART from 2000 to 2002 ( P<0.02). LD was quoted as the reason for treatment change or discontinuation for 4% of patients on cART in 2003, and for 1% of patients treated in 2006 ( P for trend <0.001). In univariate and multivariate regression analysis, patients with a weight gain of ≥5 kg were more likely to take lopinavir or atazanavir than patients without such a weight gain [odds ratio (OR) 2, 95% confidence interval (CI) 1.3–2.9, and OR 1.7, 95% CI 1.3–2.1, respectively]. Conclusions LD has become less frequent in the SHCS from 2000 to 2006. A weight gain of more than 5 kg was associated with the use of atazanavir and lopinavir. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although 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 6 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: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) 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% confidence interval [CI] -.98 to -.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (95% CI -2.72 to -.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, 95% CI -.82 to .48) or long-acting CAB/RPV (-0.64 kg, 95% CI -2.16 to .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 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV., Competing Interests: Potential conflicts of interest . P. E. T. received grants, and educational and advisory fees to institution from Gilead, MSD, and ViiV outside the submitted work. O. N. T.’s institution received expenses compensation for expert opinion from ViiV Healthcare. K. E. A. D.'s institution has received research grants from Gilead Sciences and travel grants and lecture fees from Gilead and MSD. B. S. reports support to his institution for travel grants from Gilead Sciences and ViiV healthcare. G. W. reports unrestricted research grants from Gilead Sciences and Roche Diagnostics, as well as travel grants and advisory board/lecture fees from ViiV, Gilead Sciences and MSD, all paid to his institution. M. C.’s institution received research grants and payment for expert testimony from Gilead, MSD, and ViiV. E. B.'s institution received research grants from MSD, consulting fees from Moderna, payment for lectures from Pfizer AG as well as fees for the participation of E. B. to advisory boards and/or travel grants from Gilead Sciences, ViiV, MSD, Abbvie, Pfizer, AstraZeneca, Moderna, and Ely Lilly. C. B. reports participation on the Gilead advisory board on Bulevirtide. K. D. reports grants, payment for lectures, and support for meetings and/or travel from Gilead Sciences, as well as payment for expert testimony from MSD. C. A. F. reports grants from Gilead, as well as Advisory Board attendance support from Gilead, Menarini, Moderna, MSD, and ViiV. M. S. reports support for meetings and/or travel from Gilead, participation on an advisory board for Gilead Sciences, Moderna, MSD, and ViiV Healthcare. O. N. T. reports payment or honoraria for lectures from ViiV Healthcare. C. M. reports speaker honoraria from Gilead, ViiV, and MSD. P. T. reports grants and payment for lectures from Gielad, ViiV, and MSD. D. H. reports grants from Abbvie, AstraZeneka, Gilead, GSK, ViiV, MDF, and Pfizer, consulting fees from AstraZeneca, Gilead, ViiV Healthcare, and Bavarian Nordic, support for travel and/or meetings from Gilead, and payment for leadership or fiduciary role from PFMD and Positive Council. D. L. B. reports payment for lectures, consulting fees,and participation on advisory board from Gilead, ViiV, MSD, Pfizer, and consulting fees from AstraZeneka, support for attending meetings from Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, this study explored the relationship between INSTI/non-INSTI regimens, BMI changes, and DM risk., Methods: RESPOND participants were included if they had CD4, HIV RNA, and ≥ 2 BMI measurements during follow up. Those with prior DM were excluded. DM was defined as a random blood glucose ≥ 11·1 mmol/L, HbA1c ≥ 6·5%/48 mmol/mol, use of antidiabetic medication, or site reported clinical diagnosis. Poisson regression assessed the association between natural log (ln) of time-updated BMI, current INSTI/non-INSTI, and their interactions, on DM risk., Results: Among 20,865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (IQR 37-52), with a median BMI of 24 kg/m2 (IQR 22-26). There were 785 DM diagnoses with a crude rate of 0·73 (95%CI 0·68-0·78)/100 PYFU. Ln(BMI) was strongly associated with DM (adjusted incidence rate ratio (aIRR) 16·54 per log increase, 95%CI 11·33-24·13; p<0·001). Current INSTI use associated with increased DM risk (IRR 1·58, 95%CI 1·37-1·82; p<0·001) in univariate analyses, only partially attenuated when adjusted for variables including ln(BMI) (aIRR 1·48, 95%CI 1·29-1·71; p<0·001). There was no interaction between ln(BMI), INSTI and non-INSTI use, and DM (p=0·130)., Conclusions: In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Fatty liver index (FLI) and hepatic steatosis index (HSI) are serologic scores used to detect liver steatosis. However, their diagnostic performance in people with HIV (PWH) remains unclear. We performed an external validation of FLI and HSI in the Swiss HIV Cohort Study., Methods: We systematically performed vibration-controlled transient elastography (VCTE) among Swiss HIV Cohort Study participants at Bern University Hospital between November 2019 and August 2021. Individuals with viral hepatitis and pregnant women were excluded. We defined liver steatosis as controlled attenuation parameter ≥248 dB/m using VCTE. Model discrimination was assessed with the C-index and model calibration with calibration plots. A decision curve analysis was performed to compare the clinical usefulness of both scores., Results: Of 321 participants, 91 (28.4%) were female, the median age was 51.4 years (IQR, 42-59), 230 (71.7%) were Caucasian, and 164 (51.1%) had a body mass index >25 kg/m 2 . VCTE-confirmed liver steatosis was present in 158 (49.2%). Overall, 125 (38.9%) had an FLI ≥60, and 128 (39.9%) had an HSI ≥36. At these cutoffs, the C-index to diagnose liver steatosis was 0.85 for FLI (95% CI, .80-.89) and 0.78 for HSI (95% CI, .73-.83). Whereas FLI was well calibrated, HSI overestimated the risk for steatosis. Both models showed a positive net benefit, with FLI having a greater net benefit when compared with HSI., Conclusions: FLI and HSI are valid tools to detect liver steatosis in PWH. FLI should be the preferred score, given its better performance and greater clinical usefulness., Competing Interests: Potential conflicts of interest. G. W. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and AbbVie and unrestricted research grants from Gilead Sciences and Roche Diagnostics. B. S. reports support to his institution for advisory boards and travel grants from Gilead Sciences. H. F. G. has received unrestricted research grants from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, ViiV, Janssen, and Novartis; and grants from the Swiss National Science Foundation, National Institutes of Health, and Yvonne Jacob Foundation. The institutions from which H. F. has received educational grants are as follows: Gilead, ViiV, MSD, AbbVie, and Sandoz. P. E. T.'s institution has received grants, advisory fees, and/or educational fees from Gilead, ViiV, MSD, and Daiichi-Sankyo. A. R. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead, Sciences, and Pfizer and unrestricted research grants from Gilead Sciences. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Potential conflicts of interest. F. S. reports grants or contracts and stock or stock options from Certara UK Ltd, Simcyp Division (employee). P. E. T. received grants and educational and advisory fees to their institution from Gilead, MSD, and ViiV, outside the submitted work. The institution of M. C. has received research grants from Gilead, MSD, and ViiV. D. L. B. reports honoraria paid to him for advisory boards and lectures from Gilead, Merck, and ViiV, outside the submitted work. The institution of A. H. has received travel grants and congress and advisory fees from MSD, ViiV, and Gilead unrelated to this work. E. B. received consultant fees and travel grants to their institution from Gilead, MSD, ViiV, Pfizer, AbbVie, Ely Lilly, and Moderna, outside the submitted work. A. C. reports unrestricted educational grants from MSD, Gilead, and ViiV. C. M. has received speaker honoraria from MSD, ViiV, Gilead, and Pfizer unrelated to this work. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE form for disclosure of potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

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., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

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., Competing Interests: Potential conflicts of interest. P. E. T.’s institution reports grants and other fees from Gilead, Merck, and ViiV, outside the submitted work. A. C. has received unrestricted educational and research grants from MSD, Gilead, and ViiV. B. L. received personal fees from Kantonsspital Baselland, Liestal, Switzerland, during the conduct of the study and reports personal fees from Gilead and ViiV, outside the submitted work. C. M. has received speaker honoraria from ViiV, MSD, and Pfizer unrelated to this work. E. B.’s institution reports fees for advisory board participation from Gilead Sciences, ViiV Healthcare, MSD, Pfizer, Astra Zeneca, and Ely Lilly and travel grants from Gilead Sciences, ViiV Healthcare, MSD, and Abbvie, outside the submitted work. H. F. G. reports honoraria from Gilead Sciences, Merck, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis for serving on data and safety monitoring and/or advisory boards and has received a travel grant from Gilead Sciences. In addition, he has received grants from the Yvonne Jacob Foundation and unrestricted research grants from Gilead Sciences, all paid to the institution. G. W. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Abbvie and an unrestricted research grant from Gilead Sciences; all remuneration was provided outside the submitted work. I. C. S.'s institution received a lecture fee from ViiV, outside the submitted work. R. D. K. has received personal fees from Gilead Sciences, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Potential conflicts of interest . B. S. reports financial support to his institution for travel grants from Gilead Sciences and ViiV healthcare, and for advisory boards from Gilead Sciences. D. H.’s institution receives unrestricted educational grants from AbbVie, Gilead, MSD, and ViiV Healthcare, AstraZeneca, Roche, Pfizer, and GSK. D. H. has received advisory fees from Gilead and ViiV Healthcare and reports consulting fees from AstraZeneca and UCB, all outside the submitted work. D. H. also reports roles on PFMD Executive Committee, Gilde Healthcare Impact Council, EUPATI Advisory committee (chair), Positive Council (chair), and Aids-Hilfe Bern. M. S. reports support to his institution for advisory boards from Gilead, MSD, ViiV, Pfizer, and Moderna, as well as for travel grants from Gilead. P. S. reports financial support to his institution for advisory boards and travel grants from Gilead Sciences and ViiV Healthcare. E. B. reports financial support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, ViiV Healthcare, Pfizer, Ely Lilly, AstraZeneca and Moderna. E. B. also reports grants or contracts paid to institution from Merck Sharp & Dohme. All remuneration went to his home institution and not to E. B. personally, and all remuneration was provided outside the submitted work. P. E. T.’s institution reports unrestricted and educational grants from Gilead, ViiV, and MSD, and advisory fees from Gilead and ViiV, and reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MSD, ViiV, and Gilead, all outside the submitted work. H. F. G. has received unrestricted research grants from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, Johnson and Johnson, Janssen, GSK, Novartis, and ViiV Healthcare; a travel grant from Gilead and grants from the Swiss National Science Foundation, Swiss HIV Cohort Study, Swiss HIV Cohort Research Foundation, the Yvonne Jacob Foundation, and from National Institutes of Health. G. W. reports unrestricted research grants from Gilead Sciences and Roche Diagnostics, as well as travel grants and advisory board/lecture fees from ViiV, Gilead Sciences, and MSD, all paid to his institution. A. R. reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Pfizer, and an investigator-initiated trial (IIT) grant from Gilead Sciences. A. R. also reports participation on a Data Safety Monitoring Board or Advisory Board for Moderna. All remuneration went to his home institution and not to A. R. personally, and all remuneration was provided outside the submitted work. C. A. F. reports a Gilead grant for clinical and laboratory follow-up of drug substitution patients regarding HCV in our area, paid to the Department of Infectious Diseases of the Kantonsspital Aarau, Switzerland; support for Advisory Board attendance for Gilead, Menarini, Moderna, MSD, and ViiV, paid to institution. A. C. reports unrestricted educational grants from MSD, Gilead, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: Potential conflicts of interest. B. L. received personal fees from Kantonsspital Baselland (for consultancy and statistical analyses), Liestal, Switzerland, during the conduct of the study, and reports personal fees from Gilead Switzerland SARL for lectures and ViiV for advisory board service, outside the submitted work. I. C. S.'s institution received a lecture fee from ViiV, outside the submitted work. P. R., through his institution, has received independent scientific grant support from Gilead, ViiV, Merck (all investigator-initiated study grants), and Janssen, honorarium paid to institution for lecture (content fully under author's control) from Merck & Co and has served on scientific advisory boards for Gilead, ViiV, and Merck, for which his institution has received remuneration. E. B. has received consulting fees from Gilead, MSD, ViiV, Pfizer, and AbbVie and travel support from Gilead, MSD, ViiV Healthcare, Abbvie, and Pfizer AG, and reports grants or contracts from Merck Sharp & Dohme and participation on a Data Safety Monitoring Board or Advisory Board with Merck Sharp & Dohme, Gilead Sciences, ViiV Healthcare, Pfizer AG, Ely Lilly, and Moderna, all paid to their institution and all outside the submitted work. D. L. B. received honoraria for advisory boards from Gilead, ViiV, and MSD and consulting fees from ViiV, Gilead, MSD, Pfizer, and Astra Zeneka. M. C. reports grants/support from Gilead, MSD, and ViiV, payment for expert testimony from Gilead, MSD, and ViiV, and travel support from Gilead, all paid to their institution and all outside the submitted work. R. K. reports grants/support from Gilead, paid to their institution, and grants or contracts from Swiss National Science Foundation, National Institutes of Health, outside the submitted work. H. F. G., outside this study, reports grants from Gilead (unrestricted research grant), the National Institutes of Health and the Yvonne Jacob Foundation (Swiss National Science Foundation, Swiss HIV Cohort Study), all paid to their institution; personal fees as an advisor/consultant for Merck, ViiV, and Gilead, and data and safety monitoring board remuneration from Merck, paid to their institution, and a travel grant from Gilead Sciences, paid to author, and paid participation on a Data Safety Monitoring Board or Advisory Board for Merck, Gilead Sciences, ViiV, Janssen, Johnson and Johnson, Novartis, and GSK, all outside the submitted work. P. E. T.'s institution reports unrestricted and educational grants from Gilead, ViiV, and MSD, and advisory fees from Gilead and ViiV, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Gilead, ViiV, MSD, and Daiichi Sankyo, all outside the submitted work. C. M. reports speaker honoraria from MSD, ViiV, and Pfizer, unrelated to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: Declaration of interests ICS received a lecture fee to institution from ViiV, outside the submitted work. BR declares personal fees from Gilead and non-financial support from ViiV Healthcare, outside the submitted work. DLB reports honoraria paid to himself for advisory boards and lectures from Gilead, Merck, and ViiV, outside the submitted work. CM declares personal fees from ViiV, MSD, and Pfizer, outside the submitted work. EB received consultant fees and travel grants to institution from Gilead Sciences, MSD, ViiV, Pfizer, AbbVie, Ely Lilly, and Moderna, outside the submitted work. HFG has been an adviser or member of a drug safety monitoring board (with personal fees), outside of the submitted work for Merck, Gilead Sciences, ViiV, GSK, Janssen, Johnson & Johnson, and Novartis and has received unrestricted research grants and a travel grant from Gilead Sciences. JRA has received personal fees from Gilead, Janssen, ViiV, MSD, Aelix, and Theranos, outside the submitted work. BL received personal fees from Kantonsspital Baselland, Liestal, Switzerland, during the conduct of the study, and reports personal fees from Gilead, outside the submitted work. PET received grants, and educational and advisory fees to institution from Gilead, MSD, and ViiV, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: None of the authors has declared a possible conflict of interest related to this study. A.H.'s institution has received travel grants, congress and advisory fees from MSD, ViiV, and Gilead, unrelated to this work. B.B. Flury has undertaken Advisory Boards or ad hoc consultancy for Merck/MSD, Melinta/Menarini, Shionogi, and Pfizer, and has received research grants from Melinta/Menarini unrelated to this work. K.E.A.D.'s institution has received research funding unrelated to this publication from Gilead and offered expert testimony for MSD. P.T.'s institution has received grants, advisory fees, and educational grants from Gilead, MSD, and ViiV outside the submitted work. K.A.-P.’s institution has received travel grants and advisory fees from MSD, Gilead, and ViiV healthcare unrelated to this work. I.A.A. is supported by the ProMedica Foundation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Potential conflicts of interest. I. C. S.'s institution received a lecture fee from ViiV, outside the submitted work. P. E. T.'s institution reports grants, advisory fees, and support for educational activities from Gilead, ViiV, MSD, and Sankyo Daiichi, outside the submitted work. B. L. received personal fees from Kantonsspital Baselland, Liestal, Switzerland, during the conduct of the study, and reports personal fees from Gilead (for lectures), and ViiV (for participation on Advisory Board), outside the submitted work. R. R. B. reports speaker honoraria from Pfizer (personal <2000 CHF), Sanofi-Aventis (personal 2000 CHF), and GE Healthcare (personal <2000 CHF); support for attending meetings from Pfizer for Registration EAMN Congress 2021; and unpaid roles as Chair of the Nuclear Certification Sub-committee of the European Association of Cardiovascular Imaging and Programme committee member for the annual congress of the European Association of Cardiology; and Research contract with Department of Nuclear Medicine, University Hospital Zurich, Switzerland from GE Healthcare. D. L. B. reports honoraria for advisory boards, lectures and travel grants from AbbVie, Gilead, MSD, and ViiV; and consulting fees from ViiV, MSD, Gilead, Pfizer, and AstraZeneka. AC reports educational grants from AbbVie, MSD, Gilead, and ViiV healthcare; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or education events from Gilead Sciences (unrestricted), MSD, and ViiV healthcare (educational grant to institution). R. N. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Pfizer. P. A. K. reports payment for Advisory Board meeting (Date 02/05/21; Focus: myocardial perfusion tracer) from GE Healthcare; unpaid role as Vice Chair of the Swiss Society of Nucleaer Medicine; and research contract with Department of Nuclear Medicine, University Hospital Zurich, Switzerland from GE Healthcare. All other authors report no potential conflicts. All authors have prepared ICMJE forms for disclosure of potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2022 Lucas Ramanathan, Baldesberger, Dietrich, Speranza, Lüthy, Buhl, Gisin, Koch, Nicca, Suggs, Huber, Deml and Tarr.)

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/m 2 ). 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/m 2 and liver steatosis, 31 (48.4%) had MAFLD. In multivariable analyses, BMI ≥25 kg/m 2 (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., Competing Interests: Potential conflicts of interest. G. W. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences and Abbvie, and unrestricted research grants from Gilead Sciences and Roche Diagnostics. B. S. reports support to his institution for advisory boards and travel grants from Gilead Sciences. H. F. G. has received unrestricted research grants from Gilead Sciences; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, ViiV, Janssen and Novartis; and grants the Swiss National Science Foundation, National Institutes of Health, and the Yvonne Jacob Foundation. The institutions from which H. F. have received educational grants are as follows: Gilead, ViiV, MSD, Abbvie, and Sandoz. P. E. T.'s institution has received grants, advisory fees and/or educational fees from Gilead, Viiv, MSD, and Daiichi-Sankyo. C. R. is recipient of the Protected Research Time Grant for PhD students of the University of Bern. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. A. R. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead, Sciences and Pfizer, and unrestricted research grants from Gilead Sciences., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

While an increased risk of active and latent tuberculosis infection (LTBI) in people with type-2 diabetes (DM) has been demonstrated, it is less well characterized whether LTBI is associated with an increased risk of developing DM. We investigated the link between LTBI and DM in people living with HIV in the Swiss HIV Cohort Study via time-dependent Cox proportional hazards models. We found that LTBI significantly increased the risk of developing DM (HR = 1.47), which was robust across different adjustment and censoring techniques. Our results thus suggest that LTBI may be associated with an increased risk of developing DM., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In people with human immunodeficiency virus (PWH), long-term telomere length (TL) change without/with suppressive antiretroviral therapy (ART) and the contribution of genetic background to TL are incompletely understood., Methods: We measured TL change in peripheral blood mononuclear cells by quantitative polymerase chain reaction in 107 Swiss HIV Cohort Study participants with longitudinal samples available both before and during suppressive ART. We applied mixed-effects multilevel regression to obtain uni-/multivariable estimates for longitudinal TL dynamics including age, sex, and CD4/CD8 ratio. We assessed the effect of (1) individual antiretrovirals and (2) an individual TL-polygenic risk score ([TL-PRS] based on 239 single-nucleotide polymorphisms) on TL in 798 additional participants from our previous longitudinal studies., Results: During untreated human immunodeficiency virus (HIV) infection (median observation, 7.7; interquartile range [IQR], 4.7-11] years), TL declined significantly (median -2.12%/year; IQR, -3.48% to -0.76%/year; P = .002). During suppressive ART (median observation, 9.8; IQR, 7.1-11.1 years), there was no evidence of TL decline or increase (median + 0.54%/year; IQR, -0.55% to + 1.63%/year; P = .329). The TL-PRS contributed to TL change (global P = .019) but particular antiretrovirals did not (all P > .15)., Conclusions: In PWH, TL is associated with an individual PRS. Telomere length declined significantly during untreated chronic HIV infection, but no TL change occurred during suppressive ART., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This article examines the relationships between biomedicine, complementary and alternative medicine (CAM) and parents' vaccination decision-making in Switzerland. Our empirical evidence sheds light on an understudied phenomenon-parents switching from one doctor to another provider (often one offering CAM services) around issues that arise during vaccination consultations. This is important to understand since CAM is used by 25%-50% of the Swiss population and is integrated into the Swiss health-care system when offered by biomedically trained medical doctors with additional CAM training. Qualitative data gathered from in-depth semi-structured interviews with parents (N = 30) and ethnographic observations of vaccination consultations (N = 16 biomedical consultations, N = 18 CAM consultations) demonstrate how there was not always a clear-cut, direct relationship between (non)vaccination and parents' use of CAM and/or biomedicine. Borrowing from Hirschman (Exit, voice, and loyalty: Responses to decline in firms, organizations, and states, Harvard Univ. Press, 1970), we frame our analysis by using the concepts of exit, voice and loyalty to describe parents' provider selection and vaccination decision-making process, although only four families in the sample described switching solely because of vaccination-related issues. Findings add to vaccine decision-making literature by describing and analysing the underdiscussed provider-switching phenomenon and by demonstrating the importance of parents' experiences of trust, affect and choice in vaccination consultations as they pursue the best health outcomes for their children., (© 2021 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL (SHIL).)

Objective: Vaccination in pharmacies has been a key component of national vaccination strategies to facilitate vaccination access. Qualitative data on the perspectives of professional stakeholders on vaccination in pharmacies and on the professional relations of pharmacists with physicians regarding increasing immunisation rates is limited. We conducted a qualitative study in Switzerland. The main aim was to gain further insight into professional stakeholders' perspectives on vaccination counselling and administration conducted in pharmacies, and to further understand their views on physicians' and pharmacists' roles in increasing immunisation rates., Design: We conducted semistructured qualitative interviews. We coded and analysed transcripts using thematic analysis., Setting: Face-to-face interviews took place in German-speaking and French-speaking regions of Switzerland., Participants: We interviewed 14 key vaccination stakeholders including health authorities, heads of pharmacy management and professional association boards. All participants had a background in medicine or pharmacy., Results: Three main themes emerged from the qualitative data: (1) Participants viewed pharmacists as competent to provide vaccination counselling and administration based on their university training; (2) interprofessional cooperation between physicians and pharmacists on vaccination topics is limited and should be improved; and (3) pharmacists play an important role in increasing immunisation rates by facilitating vaccination access and through provision of vaccination counselling., Conclusion: By providing vaccination counselling and administering vaccines, pharmacists play an important public health role. Healthcare policies and health authorities should encourage more involvement of pharmacists and encourage interprofessional cooperation between physicians and pharmacists in order to improve vaccination counselling and increase immunisation rates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

No validated measures of vaccine hesitancy (VH) for youth vaccination currently exist. We adapted the Parent Attitudes about Childhood Vaccines survey (PACV-15) for use in youth to create the version Youth Attitudes about Vaccines survey (YAV-14 and YAV-5), then translated it into three languages (German, French, and Italian). We administered the YAV-14 to 1,003 youth aged 15-26 years in Switzerland. We used exploratory factor analysis and Mokken scale analysis to explore the psychometric properties, Cronbach's alpha to investigate the reliability for the YAV-14 and the YAV-5, but we only report results of the YAV-5 analysis here. We determined construct validity by logistic regression of the association between youth VH as measured by the YAV-5 and non-receipt of the first human papillomavirus (HPV) vaccine dose. EFA produced a single scale in German and French while two factors were obtained in Italian. All language versions fit the Mokken scale models with medium-scale strength. There was a significant association between VH and HPV vaccine non-receipt for the full sample (odds ratio (OR); 1.93, 95% confidence interval (CI); 1.31-2.85). Language-stratified analyses found a significant association between VH and non-immunization in the German-language sample. Our results demonstrate that the German version of YAV-5 is a valid and reliable scale for identifying vaccine hesitant youth regardless of sex, and the French version is a valid and reliable scale for identifying vaccine hesitant female youth. Further validation is needed for Italian and French-speaking male youth.

Objective: The aim of this study was to examine neurocognitive course over time among people with well treated HIV., Design: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up., Setting: Seven SHCS centres., Participants: Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets., Intervention: Standardized neuropsychological assessment at baseline and 2-year follow-up., Main Outcome Measure: Neurocognitive performance using Frascati criteria and mean z-scores., Results: Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/μl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement., Conclusion: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Telomere length (TL) shortens during aging, HIV seroconversion, and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI)., Methods: We measured TL in peripheral blood mononuclear cells by quantitative polymerase chain reaction in participants of the Zurich PHI Study with samples available for ≥6 years. We obtained univariable/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL., Results: In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the first (shortest), second, and third (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (P for trend = .034), and longer TL over 6 years, but only with continuous ART (P < .001), not if ART was interrupted ≥12 months (P = .408). In multivariable analysis, participants in the second and third ART delay tertile had 17.6% (5.4%-29.7%; P = .004) and 21.5% (9.4%-33.5%; P < .001) shorter TL, after adjustment for age, with limited effect modification by clinical variables., Conclusions: In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity., Methods: In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both., Results: We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P < .001). Participants with the most unfavorable clinical risk factor profile (top quintile) had an adjusted CAD-OR of 17.82 (95% confidence interval [CI], 8.19-38.76), compared with participants in the bottom quintile. Participants with the most unfavorable CAD-PRSs (top quintile) had an adjusted CAD-OR of 3.17 (95% CI, 1.74-5.79), compared with the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had an adjusted CAD-OR of 3.67 (95% CI, 2.00-6.73), compared with the bottom quintile., Conclusions: In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related, and genetic risk factors provided the most powerful CAD prediction., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with human immunodeficiency virus (HIV; PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH., Methods: We measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses., Results: We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35-.91) and OR = 0.54 (95% CI, .31-.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27-2.92), dyslipidemia OR = 1.92 (95% CI, 1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27-2.59), OR = 2.02 (95% CI, 1.34-3.04), OR = 3.42 (95% CI, 2.14-5.45), and OR = 1.66 (95% CI, 1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use., Conclusions: In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)