Search

Objectives: The aim of the study was to assess the feasibility of a national pre‐exposure prophylaxis (PrEP) programme using smartphone‐compatible data collection. Methods: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone‐compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV‐negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow‐up (number with first follow‐up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. Results: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52–137]. Retention at first follow‐up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33–47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. Conclusions: In a national PrEP programme using smartphone‐compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort. [ABSTRACT FROM AUTHOR]

Introduction: Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART., Methods and Analysis: B-Free is a multistage, randomised, multicentre, open-label, non-inferiority trial, embedded within the Swiss HIV Cohort Study and conducted in collaboration with cohorts of PWH in the Netherlands and France. Cohort participants with a history of ART change due to virologic failure and who maintain HIV virologic suppression with an ART regimen consisting of a pharmacological booster and at least two drugs from classes other than nucleoside reverse transcriptase inhibitors are included. Patients with major drug resistance mutations against DTG or DOR and individuals with chronic hepatitis B virus infection are not eligible for the study. Individuals are randomised 1:1 to either receiving co-formulated DTG/3TC and DOR once daily or continuing their boosted ART regimen. The primary outcome is the proportion of individuals lacking virologic control (HIV-RNA ≥50 cp/mL) at 48 weeks, according to the Food and Drug Administration snapshot algorithm. Changes in DDI burden (assessed using a DDI score), treatment satisfaction (assessed using the HIV Treatment Satisfaction Questionnaire), quality of life and mental health represent key secondary outcomes. Additional secondary outcomes include the proportion of individuals developing new resistance-associated mutations and changes in quality of life and mental health. In a qualitative substudy, we will conduct semistructured interviews with a subset of participants to assess their expectations and experiences towards HIV treatment and clinical research in general. Enrolling 210 individuals will provide 80% power to demonstrate non-inferiority, defined as less than 8% absolute increase in loss of viral suppression in individuals randomised to DOR/DTG/3TC (one-sided type I error rate of 0.025)., Ethics and Dissemination: The study was approved by the competent ethics committees (reference number BASEC 2023-01060) and the regulatory authority Swissmedic (reference number 701655) in Switzerland before the enrolment of the first participant. Approval by the European Medicines Agency and local ethical committees in the Netherlands and France will be obtained prior to including participants in these countries. Participant's written informed consent is obtained by the investigators before enrolment. The results of all major B-Free study outcomes will be submitted to peer-reviewed journals that enable Open Access publication., Trial Registration Number: Swiss National Clinical Trials Portal (SNCTP000005686, registered on 06 November 2023) and Clinicaltrials.gov (NCT06037564, registered on 07 September 2023)., Competing Interests: Competing interests: BS reports financial support for travel grants from Gilead Sciences and ViiV Healthcare and for advisory boards from Gilead Sciences and MSD, paid to his institution. GW has received research grants from Gilead Sciences and Roche Diagnostics, as well as fees for advisory boards and lectures from ViiV Healthcare, MSD, Roche Diagnostics and Gilead Sciences (all paid to his institution). MC’s institution received research grants and expert opinion fees from Gilead Sciences, MSD and ViiV Healthcare. DLB received money paid to himself outside of the submitted work for advisory boards and lectures from the companies Gilead Sciences, MSD, Pfizer and ViiV Healthcare and money for a research grant from the company ViiV Healthcare. The institution of EB received study grants from Merck and Gilead Sciences; it also received travel grants and fees for EB participation to advisory boards from Gilead Sciences, Merck, ViiV Healthcare, Pfizer AG, Moderna, AstraZeneca, AbbVie and Eli Lilly. DH received fees for consultancies from AstraZeneca, Bavarian Nordic, Gilead Sciences, UCB and ViiV Healthcare, a travel grant from Gilead Sciences, and institutional funding from AstraZeneca, Gilead Sciences, GSK, A. Menarini, MSD and ViiV Healthcare. MvdV has received research grants and fees for participation in advisory boards from Gilead Sciences, MSD and ViiV Healthcare, all paid to his institution. MS reports financial support for travel grants from Gilead Sciences and for advisory boards from Gilead Sciences, MSD and ViiV Healthcare, paid to his institution. AR received research grants from Gilead Sciences, paid to his institution; travel expenses from Gilead Sciences and Pfizer, paid to his institution; and honoraria for advisory board consultations from MSD and Moderna, paid to his institution. PS’s institution has received travel grants, congress and advisory fees from ViiV Healthcare and Gilead Sciences unrelated to this work. All other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The pharmacokinetics of long-acting rilpivirine has mostly been studied in clinical trials, which do not fully address the uncertainties that arise in routine clinical situations., Aims and Methods: Our population analysis aims to establish percentile curves for rilpivirine concentrations in people with HIV (PWH) followed-up in a routine clinical setting, while identifying patient-related factors that may influence rilpivirine exposure. A total of 238 PWH enrolled in our nationwide multicenter observational study contributed to 1038 concentrations (186 and 852 concentrations after oral and intramuscular injection, respectively)., Results: Rilpivirine pharmacokinetics were best described by a two-compartment model with an oral to intramuscular relative bioavailability factor. A simple zero-order absorption process was retained for oral administration while a parallel first-order absorption was used for intramuscular administration, with 27.6% of the dose released via a fast absorption pathway and the remaining fraction via a slow absorption pathway. Our model estimated that long-acting rilpivirine reaches steady-state after 2.5 years and has an elimination half-life of 18 weeks, consistent with published estimates. In females, a 45.6% reduction in the proportion of the dose absorbed via the rapid absorption pathway was observed. However, this resulted in no more than 15% difference in trough concentrations (C trough ) compared to males, which was not considered to be clinically relevant., Conclusion: Overall, our model-based simulations showed that only approximately 50% of long-acting rilpivirine C trough would be above the 50 ng/mL threshold associated with optimal therapeutic response, while approximately 85% of C trough would be above the first quartile of concentrations observed in Phase III trials (32 ng/mL)., Competing Interests: MC reports grants and payment for expert testimony from Gilead, MSD, and ViiV and support for attending meetings from Gilead, paid to his institution. DB reports honoraria for advisory boards, lectures, and travel grants from the companies Gilead, ViiV, and MSD. HG has received unrestricted research grants from Gilead Sciences and ViiV Healthcare; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, GSK, Johnson and Johnson, Janssen, Novartis, and ViiV Healthcare; and grants from the Yvonne Jacob Foundation, from the National Institutes of Health, and unrestricted research grants from Gilead Sciences. The institution of JD received grants from Gilead Sciences and ViiV. BS reports support for travel grants and advisory boards from Gilead Sciences and ViiV, paid to his institution. The institution of HF received educational grants from ViiV, MSD, AbbVie, Gilead, and Sandoz. MS reports advisory board payments to his institution by Gilead, MSD, ViiV, Moderna, and Pfizer. The institution of AR received grants from Gilead, support for attending meetings from Gilead and Pfizer, and advisory board fees from MSD and Moderna. CM has received speaker honoraria from ViiV, MSD, and Gilead. CD received travel grants for congress participation from Gilead. The institution of EB received grants from the Swiss National Science Foundation; grants from MSD; support for attending meetings from Gilead, MSD, ViiV, and Pfizer; and advisory board fees from Gilead, MSD, ViiV, Pfizer, Moderna, AstraZeneca, Abbvie, and Lilly. The institution of PS received honoraria for advisory board participation and support for attending meetings from ViiV and Gilead. None of those grants and supports was related to the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Thoueille, Saldanha, Schaller, Choong, Veuve, Munting, Cavassini, Braun, Günthard, Duran Ramirez, Surial, Furrer, Rauch, Ustero, Calmy, Stöckle, Di Benedetto, Bernasconi, Schmid, Marzolini, Girardin, Buclin, Decosterd and Guidi.)

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.)

The REPRIEVE trial suggests that primary cardiovascular disease (CVD) prevention could be considered among people with HIV at low CVD risk. We found cisgender women with low/moderate and high CVD risk are less likely to receive statins than cisgender men. Efforts are needed to guarantee equal access to statin-based CVD prevention., Competing Interests: Potential conflicts of interests. I.A.A. has received honoraria from MSD and Sanofi, a travel grant from Gilead Sciences, and a grant from the Promedica foundation. R.D.K. has received research fundings from Gilead unrelated to this work. K.A.P.'s institution has received travel grants and advisory fees from MSD, Gilead, and ViiV healthcare unrelated to this work. H.F.G. has received grants from the SNF, SHCS, Yvonne Jacob Foundation, University of Zurich's Clinical Research Priority Program, viral disease; Zurich Primary HIV Infection; Bill and Melinda Gates Foundation; National Institutes of Health; Gilead Sciences, ViiV Healthcare; and Roche; and personal fees from Merck, Gilead Sciences, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis, for consultancy or DSMB membership and a travel grant from Gilead. C.M. received speaker honoraria from Gilead and ViiV unrelated to this work. M.S. received advisory fees from Gilead, MSD, Moderna, Pfizer, and ViiV healthcare unrelated to this work and a travel grant from Gilead. E.B.'s institution received research grants from SHCS, Swiss National Science Foundation, Gilead, and Merck; advisory fees and travel grants from Gilead, Merck, ViiV, Pfizer, Abbvie, Moderna, Astra Zeneca, and Ely Lilly unrelated to the present work. B.S. reports support to his institution for travel grants from Gilead Sciences and ViiV healthcare, and for advisory boards from MSD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.)

Long-acting cabotegravir has been studied mainly in the stringent framework of clinical trials, which does not necessarily reflect the situation of people with HIV (PWH) in routine clinical settings. The present population pharmacokinetic analysis aims to build real-world reference percentile curves of cabotegravir concentrations, accounting for patient-related factors that may affect cabotegravir exposure. The second objective is to simulate whether dosing interval adjustments of cabotegravir could be considered in specific subpopulations. Overall, 238 PWH contributed to 1,038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). Cabotegravir pharmacokinetics was best described using a one-compartment model with distinct first order-absorption for oral and intramuscular administrations, and identical volume and clearance. Our model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady-state of 8 months and an elimination half-life of 4.6 weeks for long-acting cabotegravir. Sex and body mass index significantly influenced absorption, and bodyweight affected clearance. Model-based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4-fold protein-adjusted 90% inhibitory target concentration., (© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: People with HIV and extensive antiretroviral exposure may have limited/exhausted treatment options (LExTO) due to resistance, comorbidities, or antiretroviral-related toxicity. Predictors of LExTO were investigated in the RESPOND cohort., Methods: Participants on ART for at least 5 years were defined as having LExTO when switched to at least two anchor agents and one third antiretroviral (any class), a two-drug regimen of two anchor agents (excluding rilpivirine with dolutegravir/cabotegravir), or at least three nucleoside reverse transcriptase inhibitors. Baseline was the latest of January 1, 2012, cohort enrolment or 5 years after starting antiretrovirals. Poisson regression modeled LExTO rates and clinical events (all-cause mortality, non-AIDS malignancy, cardiovascular disease [CVD], and chronic kidney disease [CKD])., Results: Of 23 827 participants, 2164 progressed to LExTO (9.1%) during 130 061 person-years follow-up (PYFU); incidence 1.66/100 PYFU (95% CI 1.59-1.73). Predictors of LExTO were HIV duration more than 15 years (vs. 7.5-15; adjusted incidence rate ratio [aIRR] 1.32; 95% CI 1.19-1.46), development of CKD (1.84; 1.59-2.13), CVD (1.64; 1.38-1.94), AIDS (1.18; 1.07-1.30), and current CD4 + cell count of 350 cells/μl or less (vs. 351-500 cells/μl, 1.51; 1.32-1.74). Those followed between 2018 and 2021 had lower rates of LExTO (vs. 2015-2017; 0.52; 0.47-0.59), as did those with baseline viral load of 200 cp/ml or less (0.46; 0.40-0.53) and individuals under 40. Development of LExTO was not significantly associated with clinical events after adjustment for age and current CD4, except CKD (1.74; 1.48-2.05)., Conclusion: Despite an aging and increasingly comorbid population, we found declining LExTO rates by 2018-2021, reflecting recent developments in contemporary ART options and clinical management. Reassuringly, LExTO was not associated with a significantly increased incidence of serious clinical events apart from CKD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

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 and Aims: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study., Methods: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA., Results: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY., Conclusions: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported., Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023., Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load., Interpretation: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated., Funding: This work was funded by the Swiss National Science Foundation, grant number N ◦ 324730&#95;192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers)., Competing Interests: M.C. reports grants and payment for expert testimony from Gilead, MSD and ViiV, and support for attending meetings from Gilead, paid to his institution outside of the submitted work. D.B. has received honoraria for advisory board from the companies Gilead, MSD, and ViiV, and support for attending meetings from ViiV and Gilead. 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, Johnson and Johnson, Janssen, Novartis, and ViiV Healthcare; and grants from the Swiss National Science Foundation, the Yvonne Jacob Foundation, from National Institutes of Health and unrestricted research grants from Gilead Sciences. B.S. reports support for travel grants and advisory boards from Gilead Sciences and ViiV, paid to his institution outside of the submitted work. The institution of H.F. received educational grants from ViiV, MSD, AbbVie, Gilead, and Sandoz paid to the institution. M.S. reports advisory board paid to his institution by Gilead, MSD, ViiV, Moderna and Pfizer. The institution of A.R. received grants from Gilead; support for attending meetings from Gilead and Pfizer; and advisory boards from MSD and Moderna. C.M. has received speaker honoraria from ViiV, MSD, and Gilead unrelated to this work. C.D.B. received travel grant for congress participation from Gilead. The institution of E.B. received grants from the Swiss National Science Foundation; grants from MSD; support for attending meetings from Gilead, MSD, ViiV and Pfizer; and advisory boards from Gilead, MSD, ViiV, Pfizer, Moderna, AstraZeneca, Abbvie and Lilly. The institution of P.S. received honoraria for advisory board and support for attending meetings from ViiV and Gilead. The other authors declare no conflict of interest., (© 2023 The Author(s).)

Background: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events., Methods: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates., Findings: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52)., Interpretation: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV., Funding: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism., Competing Interests: Declaration of interests SMR, RWL, and SMI report National Institutes of Health (NIH) grants paid to their institution during the conduct of the study. SL reports grants from the NIH and the Providence/Boston Center for AIDS Research. MAH reports grants from the NIH and personal honoraria from Cytel, ProPublica, and ADIA Lab. JACS reports grants from the NIH and UK National Institute for Health and Care Research (NIHR). AP received grants from the Wellcome Trust, the Bill & Melinda Gates Foundation, the NIH, and UK NIHR and payments from the Gates Foundation outside of the study. FB reports grants and personal fees from Gilead Sciences, outside the submitted work. IJ reports payments from Gilead Sciences, GESIDA, and ViiV Healthcare. MJG participated on advisory boards for Merck, Gilead, and ViiV. MBK has received grants and honoraria from ViiV Healthcare, AbbVie, and Gilead. LM reports grants from ANRS-MIE INSERM paid to her institution. RL received grants from Canadian Institutes of Health Research, Alberta Innovates, and the University of Calgary outside of the study. PR reports grants from Gilead Sciences, ViiV Healthcare, and Merck & Co. CAS and MvdV report grants and honoraria from Gilead Sciences, ViiV Healthcare, and MSD outside of the submitted work. BS reports financial support to his institution for travel grants from Gilead Sciences and ViiV healthcare, and for advisory boards from Gilead Sciences. GT received grants from Gilead Sciences and University College London and EU and national funds. AvS reports grants from the Dutch Ministry of Health, Welfare, and Sport and the European Centre for Disease Prevention and Control. LW received grants from ANRS-MIE. JMM has received consulting honoraria and research grants from Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work. JMM has also received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain, during 2017–24. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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.)

Objectives: Access to affordable STI testing for asymptomatic persons is important to reduce STI transmission. Our testing site offers easily accessible and affordable STI testing for the general population irrespective of symptoms. Here we report STI prevalence and motivational factors of attendance., Methods: Between 2017 and 2019, all participants at our STI testing site at the University Hospital Bern, Switzerland, were interviewed with a computer-based self-completion questionnaire. Pooled (oral, genital and anal) swabs were tested for Chlamydia trachomatis , Neisseria gonorrhoeae and blood samples for syphilis and HIV. People's motivational factors to attend were assessed using a standardised questionnaire., Results: 5402 individuals between 17 and 82 (median 33.5) years were included. Of those, 2550 (47.2%) were between 25 and 34 years old and 3133 were heterosexual (58%), with rising attendance over the years. One-third attended because of a new sexual relationship, and one-third reported condomless sex. Among all individuals, we found 191 (3.8%) new chlamydia infections (89/191 in females and 101/191 in males) and 54 (1.1%) gonorrhoea infections (44/54 in males). In addition, 52/5125 tested individuals (0.8%) had syphilis requiring treatment.The number of sexual partners, previous bacterial STIs and condomless sex were associated with having an STI. Four heterosexual individuals were newly diagnosed with HIV. People rated a low threshold offer (through online booking or telephone) and personal counselling as most important factors to attend the service., Conclusion: We found many asymptomatic bacterial STIs requiring treatment. Offering easily accessible STI testing and counselling proved successful as shown by increasing rates of attendance and high levels of satisfaction., Competing Interests: Competing interests: The institution of KA-P has received travel grants and advisory fees from MSD, Gilead and ViiV healthcare. BS reports support to his institution for advisory boards and travel grants from Gilead Sciences and ViiV. HF’s institution has received educational grants from Gilead, MSD, ViiV, Abbvie and Sandoz paid to the institution. AR reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, Pfizer and Abbvie, and an investigator initiated trial grant from Gilead Sciences. All remuneration went to his home institution and not to AR personally, and all remuneration was provided outside the submitted work., (© 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 & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection., Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves., Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals., Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening., Impact and Implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In the Swiss HIV Cohort Study, 61 of 222 (27%) HIV-suppressed persons with chronic hepatitis B virus (HBV) infection had HBV replication after 2 years on tenofovir, of whom 77% were suppressed thereafter. Self-reported adherence to therapy and HBV viral load at tenofovir initiation were predictors of persistent replication., Competing Interests: Potential conflicts of interest . E. H. reports support for attending meetings and/or travel from Gilead Sciences and ViiV Healthcare (paid to institution). B. S. reports a grant from Institutional Grant Inselspital Bern, support for attending meetings and/or travel from Gilead Sciences and ViiV Healthcare (paid to institution), and participation on a data and safety monitoring board (DSMB) or advisory board for Gilead Sciences (paid to institution). H. F. G. reports grants from National Institute of Health (NIH) and the Yvonne Jacob Foundation; an unrestricted research grant from Gilead Sciences (paid to institution); and participation on a DSMB or advisory board for Merck, Gilead Sciences, Janssen, ViiV Healthcare, GSK, and Novartis (paid to author). M. S. reports participation on a DSMB or advisory board for Gilead Sciences, ViiV Healthcare, Moderna, MSD, and Pfizer. E. B. reports grants or contracts from Merck Sharp and Dohme (paid to institution); support for attending meetings and/or travel from AbbVie, Gilead Sciences, Merck Sharp and Dohme, Pfizer AG, and ViiV Healthcare (paid to institution); and participation on a DSMB or advisory board for Gilead Sciences, Merck Sharp and Dohme, Pfizer AG, ViiV Healthcare, Ely Lilly, and Astra Zeneca (Paid to institution). P. S. has received consulting/advisory board membership fees from Gilead Sciences. A. C. reports grants from Gilead Sciences, ViiV Healthcare, MSD (unrestricted educational grant; Groupe LIPO et métabolisme; grant to institution), and MSD (research grant). A. R. reports serving on advisory boards for Gilead Sciences and MSD (paid to institution), travel grants from Gilead Sciences and Pfizer, and research support by an investigator-initiated trial grant from Gilead Sciences (all renumeration went to institution). G. W. reports grants or contracts from Gilead Sciences and Roche Diagnostics (paid to institution); payment or honoraria for lectures, presentations, speakers and bureaus, manuscript writing, or educational events from Gilead Sciences and MSD (paid to institution). All remaining authors: No reported 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) 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.)

Objective: The aim was to assess the impact of operating room (OR) ventilation quality on surgical site infections (SSIs) using a novel ventilation index., Background: Previous studies compared laminar air flow with conventional ventilation, thereby ignoring many parameters that influence air flow properties., Methods: In this cohort study, we surveyed hospitals participating in the Swiss SSI surveillance and calculated a ventilation index for their ORs, with higher values reflecting less turbulent air displacement. For procedures captured between January 2017 and December 2019, we studied the association between ventilation index and SSI rates using linear regression (hospital-level analysis) and with the individual SSI risk using generalized linear mixed-effects models (patient-level analysis)., Results: We included 47 hospitals (182 ORs). Among the 163,740 included procedures, 6791 SSIs were identified. In hospital-level analyses, a 5-unit increase in the ventilation index was associated with lower SSI rates for knee and hip arthroplasty (-0.41 infections per 100 procedures, 95% confidence interval: -0.69 to -0.13), cardiac (-0.89, -1.91 to 0.12), and spine surgeries (-1.15, -2.56 to 0.26). Similarly, patient-level analyses showed a lower SSI risk with each 5-unit increase in ventilation index (adjusted odds ratio 0.71, confidence interval: 0.58-0.87 for knee and hip; 0.72, 0.49-1.06 for spine; 0.82, 0.69-0.98 for cardiac surgery). Higher index values were mainly associated with a lower risk for superficial and deep incisional SSIs., Conclusions: Better ventilation properties, assessed with our ventilation index, are associated with lower rates of superficial and deep incisional SSIs in orthopedic and cardiac procedures. OR ventilation quality appeared to be less relevant for other surgery types., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

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: ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised., Methods: In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection., Results: We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461)., Conclusions: The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts., Methods: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline., Results: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline., Conclusion: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

SHCS#879 is an ongoing Switzerland-wide multicenter observational study conducted within the Swiss HIV Cohort Study (SHCS) for the prospective follow-up of people living with HIV (PLWH) receiving long-acting injectable cabotegravir-rilpivirine (LAI-CAB/RPV). All adults under LAI-CAB/RPV and part of SHCS are enrolled in the project. The study addresses an integrated strategy of treatment monitoring outside the stringent frame of controlled clinical trials, based on relevant patient characteristics, clinical factors, potential drug-drug interactions, and measurement of circulating blood concentrations. So far, 91 blood samples from 46 PLWH have been collected. Most individuals are less than 50 years old, with relatively few comorbidities and comedications. The observed concentrations are globally in accordance with the available values reported in the randomized clinical trials. Yet, low RPV concentrations not exceeding twice the reported protein-adjusted 90% inhibitory concentration have been observed. Data available at present confirm a considerable between-patient variability overall. Based on the growing amount of PK data accumulated during this ongoing study, population pharmacokinetic analysis will characterize individual concentration-time profiles of LAI-CAB/RPV along with their variability in a real-life setting and their association with treatment response and tolerability, thus bringing key data for therapeutic monitoring and precision dosage adjustment of this novel long-acting therapy., Competing Interests: D.B. received honoraria for advisory board from the companies Gilead, MSD, Pfizer, and ViiV. 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, Novartis, and ViiV Healthcare; and grants from the Swiss National Science Foundation, the Yvonne Vontobel Foundation and from National Institutes of Health. B.S. reports support to his institution for advisory boards and travel grants from Gilead Sciences and ViiV. The institution of H.F. received educational grants from ViiV, MSD, AbbVie, Gilead, and Sandoz paid to the institution. M.S. reports advisory board paid to his institution by Gilead, MSD, and ViiV and grant to participate at conferences paid to his institution by Gilead. A.C. received a research grant from MSD, and educational grants from Gilead, MSD, and ViiV. C.M. has received speaker honoraria from ViiV and MSD unrelated to this work. The other authors declare no conflict of interest.

Background: Changes in mental and sexual health among men having sex with men (MSM) due to the SARS-CoV-2 pandemic remain unclear., Methods: Design: Longitudinal analysis of an ongoing, multicentre, pre-exposure prophylaxis (PrEP) cohort (NCT03893188) in Switzerland. Participants: HIV-negative MSM aged ≥18 who completed at least one questionnaire before and one after the start of the SARS-CoV-2 pandemic. Outcomes: Primary: mental health, defined as anxiety and depression scores assessed by the Patient Health Questionnaire-4. Secondary: sexual behaviour, well-being, PrEP use and disruption of care. Outcomes were assessed over seven periods corresponding to different SARS-CoV-2 prevention measures in Switzerland. We performed pairwise comparisons between periods (Wilcoxon signed rank test)., Results: Data from 1,043 participants were included. Whilst anxiety scores remained stable over time, depression scores worsened in the second wave and the second lockdown period compared to pre-pandemic scores. This was confirmed by pairwise comparisons (pre-SARS-CoV-2/second wave and pre-SARS-CoV-2/second lockdown: p <0.001). Downward trends in sexual activity,sexualized substance use, and a switch from daily to "event-driven" PrEP were found. Disruption of care affected 42.6% (790/1856) of daily PrEP users' follow-up visits., Conclusion: In this longitudinal analysis of a PrEP cohort enrolling MSM, depression scores worsened in the second wave and the second lockdown compared to the pre-pandemic period.

Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immune response with regard to neuronal injury has not yet been investigated., Methods: In a prospective cohort study, we recruited patients with mild-moderate ( n  = 39) and severe ( n  = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses., Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild-moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild-moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies., Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.C.S. and T.S. report grants from Orion Pharma, Abbott Nutrition International, B. Braun Medical, CSEM, Edwards Lifesciences Services, Kenta Biotech, Maquet Critical Care, Omnicare Clinical Research, Nestle, Pierre Fabre Pharma, Pfizer, Bard Medica, Abbott, Anandic Medical Systems, Pan Gas Healthcare, Bracco, Hamilton Medical, Fresenius Kabi, Getinge Group Maquet, Dräger, Teleflex Medical, GlaxoSmithKline, Merck Sharp and Dohme, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Hemotune, Phagenesis, and Nycomed, outside the submitted work. D.L. is CMO of GeNeuro; he has received personal compensation for consulting and speaking, and travel reimbursement from Quanterix, Roche, Novartis, Orion, GeNeuro, and Sanofi, outside the submitted work. J.K. reports grants from Biogen, Novartis, Roche, Swiss MS Society, Sanofi, University of Basel, Swiss National Research Foundation, Merck, and Celgene, outside the submitted work. D.L. is CMO of GeNeuro; he has received personal compensation for consulting and speaking, and travel reimbursement from Quanterix, Roche, Novartis, Orion, GeNeuro, and Sanofi, outside the submitted work. S.L.L. reports grants from Swiss National Science Foundation, European Union’s Horizon 2020 research and innovation program, and HEARit Eureka Eurostars/European Commission, outside the submitted work., (© The Author(s), 2022.)

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., (© 2021 British HIV Association.)

Background: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain., Objective: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF., Design: Cohort study., Setting: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland., Participants: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer., Measurements: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions Z tests., Results: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months., Limitation: Short follow-up, small subgroup analyses, and potential residual confounding., Conclusion: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels., Primary Funding Source: Swiss National Science Foundation.

Background & Aims: Chronic hepatitis B virus (HBV) infection accounts for 30%-50% of cirrhosis related deaths in sub-Saharan Africa (SSA). Since HBV-related cirrhosis is an indication for immediate antiviral therapy and cancer surveillance, we aimed to estimate the prevalence of cirrhosis among treatment-naïve patients with chronic HBV infection in SSA., Methods: We performed a systematic review of published articles which evaluated liver fibrosis stage among treatment-naïve HBV-infected individuals who presented to care in SSA. Our primary outcome was the prevalence of cirrhosis in HBsAg-positive persons, which was estimated using random-effects meta-analysis. Risk factors for cirrhosis were explored using subgroup-analyses and multivariable meta-regression., Results: Of 2129 articles identified, 17 met our eligibility criteria. The studies described 22 cohorts from 13 countries, including 13 cohorts (3204 patients) with chronic HBV mono-infection and nine cohorts (688 patients) with HIV/HBV-coinfection. Liver fibrosis was assessed using transient elastography (10 cohorts), APRI score (11 cohorts), and Fibrotest (one cohort). The pooled prevalence of cirrhosis was 4.1% (95% confidence interval [CI] 2.6-6.4) among studies from primary care facilities or general population, compared to 12.7% (95% CI 8.6-18.3) in studies performed in referral or tertiary care facilities (adjusted odds ratio 0.29, 95% CI 0.15-0.56). We found no association between cirrhosis and age, gender, fibrosis test used or HIV-coinfection., Conclusions: Depending on the setting, between 4% and 13% of HBV-infected individuals in SSA have cirrhosis and need immediate antiviral therapy. These estimates should be considered when planning HBV treatment strategies and resource allocation., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

Whereas excessive alcohol consumption increases liver disease incidence and mortality, evidence on the risk associated with specific drinking patterns is emerging. We assessed the impact of binge drinking on mortality and liver disease in the Swiss HIV Cohort Study. All participants with follow-up between 2013 and 2020 were categorized into one of four drinking pattern groups: "abstinence", "non-hazardous drinking", "hazardous but not binge drinking" (Alcohol Use Disorder Identification Test Consumption [AUDIT-C] score ≥ 3 in women and ≥4 in men), and "binge drinking" (≥6 drinks/occasion more than monthly). We estimated adjusted incidence rate ratios (aIRR) for all-cause mortality, liver-related mortality and liver-related events using multivariable quasi-Poisson regression. Among 11,849 individuals (median follow-up 6.8 years), 470 died (incidence rate 7.1/1000 person-years, 95% confidence interval [CI] 6.5-7.8), 37 experienced a liver-related death (0.6/1000, 0.4-0.8), and 239 liver-related events occurred (3.7/1000, 3.2-4.2). Compared to individuals with non-hazardous drinking, those reporting binge drinking were more likely to die (all-cause mortality: aIRR 1.9, 95% CI 1.3-2.7; liver-related mortality: 3.6, 0.9-13.9) and to experience a liver-related event (3.8, 2.4-5.8). We observed no difference in outcomes between participants reporting non-hazardous and hazardous without binge drinking. These findings highlight the importance of assessing drinking patterns in clinical routine.

Sexually transmitted anorectal infections Abstract. In recent years, the incidence of sexually transmitted infections in Switzerland has increased significantly for various reasons. They often manifest with anorectal symptoms, and may present as localized lesions, proctitis, or enteritis. To avoid misdiagnosis and stop transmissions to their sexual partners, testing for sexually transmitted diseases is indicated in most individuals with anorectal symptoms. This article provides an overview of the diagnosis and treatment of sexually transmitted anorectal infections.

Background: Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear., Methods: We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series., Results: Among 106 participants (15.1% women, median age 53 years), eGFR was 60-89 mL/min/1.73 m in 84 (79.2%) and <60 mL/min/1.73 m in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m experienced increases in eGFR of 3.2 mL/min/1.73 m (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m experienced improvements of 6.2 mL/min/1.73 m (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (-6.3 mg/mmol, 95% CI -10.0 to -2.7), and ALT levels declined in patients with elevated baseline levels (-11.8 IU/L, 95% CI -17.3 to -6.4) 1 year after replacing TDF with TAF., Conclusions: Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels.

Background: Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) improves renal tubular markers in HIV-infected individuals but the impact on estimated glomerular filtration rate (eGFR) remains unclear., Methods: In all participants from the Swiss HIV Cohort Study who switched from TDF to TAF-containing antiretroviral regimen or continued TDF, we estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months using mixed-effect models., Results: Of 3520 participants (26.6% women, median age 50 years), 2404 (68.5%) switched to TAF. Overall, 1664 (47.3%) had an eGFR <90 mL/min and 1087 (30.9%) an UPCR ≥15 mg/mmol. In patients with baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (-1.7 mL/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% confidence interval [CI], .5-2.5) if the baseline eGFR was 60-89 mL/min, and 4.1 mL/min (95% CI, 1.6-6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI, 2.3-9.3) with continued use of TDF in individuals with baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR., Conclusions: Switching from TDF to TAF improves eGFR and proteinuria in patients with renal dysfunction., (© 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.)

Background: Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function., Methods: We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF., Results: We included 5'012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2'796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07-1.50), age > 50 years (1.43, 1.23-1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77-2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09-0.13), those treated in non-tertiary care centers (0.56, 0.46-0.70), as well as those with CD4 cell counts below 500/μL (0.77, 0.66-0.90) and with chronic hepatitis C infection (0.66, 0.54-0.80) were most likely to stay on TDF., Conclusions: Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.