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Laser assisted in situ keratomileusis (LASIK) surgery is the leading and most performed refractive surgery nowadays. A possible complication of LASIK surgery is infectious keratitis which can lead to disastrous corneal damage and result in permanent loss of vision. LASIK procedures have become increasingly accessible, and the demand for refractive surgery has risen among patients, challenging the medical field to improve the prevention of post-operative infections. Nevertheless, a wide range of pathogens have been described as responsible for post-LASIK keratitis. However, non-tuberculous mycobacterial keratitis remains an infrequent occurrence and is poorly described in the literature. To the best of our knowledge, this is the first ever reported case of post-LASIK keratitis caused by Mycobacterium wolinskyi. We describe the clinical and microbial characteristics, leading to its challenging treatment choice., (© 2024. The Author(s).)

Background: Although sex hormones are recognized to induce immune variations, the effect of hormonal therapy use on immunity is only poorly understood. Here, we quantified how hormonal therapy use affects HIV-1 immune markers in cis women (CW) and trans women and non-binary people (TNBP) with HIV., Methods: We considered CD4, CD8 and lymphocyte measurements from cis men (CM), CW and TNBP in the Swiss HIV Cohort Study. We modelled HIV-1 markers using linear mixed-effects models with an interaction between 'gender' (CW, TNBP) and 'hormonal therapy use' (yes/no). Models were adjusted on age, ethnicity, education level, time since start of antiretroviral therapy and use of intravenous drugs. We assessed the inflammatory effect of hormonal therapy use in 31 TNBP using serum proteomics measurements of 92 inflammation markers., Results: We included 54 083 measurements from 3092 CW and 83 TNBP, and 147 230 measurements from 8611 CM. Hormonal therapy use increased CD4 count and CD4:CD8 ratio in TNBP more than in CW (p interaction  = 0.02 and 0.007, respectively). TNBP with hormonal therapy use had significantly higher CD4 counts [median = 772 cells/μL, interquartile range (IQR): 520-1006] than without (617 cells/μL, 426-892). This was similar to the effect of CW versus CM on CD4 T cells. Hormonal therapy use did not affect serum protein concentrations in TNBP., Conclusion: This study highlights the potential role of hormonal therapy use in modulating the immune system among other biological and social factors, especially in TNBP with HIV., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

The number of elderly people is constantly increasing in Switzerland. This population is often at higher risk of infections and concomitant decompensation of underlying comorbidities, in particular cardiac or respiratory diseases. Vaccines are some of the most effective preventive measures for limiting morbidity and mortality related to some of those infections, such as influenza or shingles. In order to improve vaccination coverage, it is essential to inform the patients of the benefits of vaccination, and to plan a catch-up vaccination consultation. The goal of this article is to offer a practical guide for the general practitioner detailing vaccines for the elderly recommended in Switzerland., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

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: 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.)

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.)

Reactive oxygen species (ROS) play a crucial role in the cellular defense against S. aureus , as evidenced by the importance of this pathogen in patients lacking the ROS-generating phagocyte NADPH oxidase NOX2. ROS concentrations required to kill S. aureus in vitro are much higher than those found in the phagosome. We therefore hypothesized that sublethal ROS concentrations may play a role in S. aureus gene dysregulation and investigated the in vitro transcriptomic response of S. aureus to sublethal concentrations of hydrogen peroxide (H 2 O 2 ). A striking observation of these experiments was a coordinated and massive downregulation of genes involved in pyrimidine metabolism. Using transposon insertion mutants, we demonstrated that deletion of carA , a gene involved in pyrimidine synthesis, led to a significant growth defect and to an increased sensitivity of S. aureus to added H 2 O 2 . The phenotype of the carA mutant could be reversed through supplementation with the pyrimidine precursor uracil, or with a multicopy vector encoding carA . As opposed to the impact of ROS on extracellular survival, carA deletion did not affect the intracellular survival in neutrophils. Our results raise the possibility that ROS-dependent downregulation of pyrimidine metabolism might be a survival strategy of S. aureus , allowing colonization through intracellular survival, while decreasing the risk of killing the host through dampened extracellular growth., Competing Interests: The 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 © 2021 Buvelot, Roth, Jaquet, Lozkhin, Renzoni, Bonetti, Gaia, Laumay, Mollin, Stasia, Schrenzel, François and Krause.)

Background: In people with human immunodeficiency virus (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction (ie, estimated glomerular filtration rate [eGFR] decrease of >5mL/min/1.73m2 per year for ≥3 consecutive years)., Methods: We obtained univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D chronic kidney disease (CKD) risk score, antiretroviral exposures, and a polygenic risk score based on 14 769 genome-wide single nucleotide polymorphisms in white Swiss HIV Cohort Study participants., Results: We included 225 participants with rapid progression and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with low D:A:D risk, participants with high risk had rapid progression (HR =  1.82 [95% CI, 1.28-2.60]). Compared to the first (favorable) polygenic risk score quartile, participants in the second, third, and fourth (unfavorable) quartiles had rapid progression (HR = 1.39 [95% CI, 0.94-2.06], 1.52 [95% CI, 1.04-2.24], and 2.04 [95% CI, 1.41-2.94], respectively). Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR = 1.36 [95% CI, 1.06-1.76])., Discussion: An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk 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.)

The current COVID-19 pandemic is the main topic of news worldwide by its magnitude and consequences across the entire planet. From a medical point of view, several risk factors for developing severe illness have been reported in the literature, notably an immunosuppressed status. For people living with HIV, several questions have been raised concerning not only their vulnerability, but also in relation to an eventual protection conferred by antiretroviral therapy. This article will address these two pandemics by looking at the potential impact of SARS-CoV-2 on people living with HIV and, in parallel, exploring similarities and differences in terms of treatment, potential for recovery, prevention and their impact on clinical research. We review also future novel therapies for the treatment of HIV., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project « PIRATE » indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published., Competing Interests: Angela Huttner a mené le projet suisse PIRATE, financé entièrement par une subvention du Fonds national suisse. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Reactive oxygen species (ROS) are highly reactive oxygen derivatives. Initially, they were considered as metabolic by-products (of mitochondria in particular), which consistently lead to aging and disease. Over the last decades, however, it became increasingly apparent that virtually all eukaryotic cells possess specifically ROS-producing enzymes, namely, NOX NADPH oxidases. In most mammals, there are seven NOX isoforms: three closely related isoforms, NOX1, 2, 3, which are activated by cytoplasmic subunits; NOX4, which appears to be constitutively active; and the EF-hand-containing Ca 2+ -activated isoforms NOX5 and DUOX1 and 2. Loss-of-function mutations in NOX genes can lead to serious human disease. NOX2 deficiency leads to primary immune deficiency, while DUOX2 deficiency presents as congenital hypothyroidism. Nox-deficient mice provide important tools to explore the physiological functions of various NADPH oxidases as a loss of function in Nox2, Nox3, and Duox2 leads to a spontaneous phenotype. The genetic absence of Nox1, Nox4, and Duox1 does not result in an obvious mouse phenotype (the NOX5 gene is absent in rodents and can therefore not be studied using knockout mice). Since the discovery of the NOX family at the turn of the millennium, much progress in understanding the biochemistry and the physiology of NOX has been made; however many questions remain unanswered to date. This chapter is an overview of our present knowledge on mammalian NOX/DUOX enzymes.

Dysfunction of phagocytes is a relevant risk factor for staphylococcal infection. The most common hereditary phagocyte dysfunction is chronic granulomatous disease (CGD), characterized by impaired generation of reactive oxygen species (ROS) due to loss of function mutations within the phagocyte NADPH oxidase NOX2. Phagocytes ROS generation is fundamental to eliminate pathogens and to regulate the inflammatory response to infection. CGD is characterized by recurrent and severe bacterial and fungal infections, with Staphylococcus aureus as the most frequent pathogen, and skin and lung abscesses as the most common clinical entities. Staphylococcus aureus infection may occur in virtually any human host, presumably because of the many virulence factors of the bacterium. However, in the presence of functional NOX2, staphylococcal infections remain rare and are mainly linked to breaches of the skin barrier. In contrast, in patients with CGD, S. aureus readily survives and frequently causes clinically apparent disease. Astonishingly, little is known why S. aureus, which possesses a wide range of antioxidant enzymes (e.g. catalase, SOD), is particularly sensitive to control through NOX2. In this review, we will evaluate the discovery of CGD and our present knowledge of the role of NOX2 in S. aureus infection., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chickenpox is a generally benign condition during childhood, but it can cause severe complications when affecting teenage or adult patients. Immunodeficiency and pregnancy are risk factors for disseminated disease with pulmonary, neurological and/or hepatic involvement. Reinfection may be more frequent than previously thought, and management is identical to that of primary infection. The most common manifestation of viral reactivation is shingles, but it can also cause meningitis and vasculopathy, as well as disseminated herpes zoster in the immunocompromised patient. In this article, we will review the clinical manifestations and management of VZV infection in adults.