Publications by authors named "Alexandra Calmy"

266 Publications

The association between depressive symptoms and neurocognitive impairment in people with well-treated HIV in Switzerland.

Int J STD AIDS 2021 Feb 25:956462420987434. Epub 2021 Feb 25.

Infectious Diseases Service, 30635Lausanne University Hospital, Lausanne, Switzerland.

Background: Depression may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Attributing NCI to depression rather than to HIV is complicated as depression may be both a causal factor and an effect of NCI. This study aimed to determine the association between depressive symptoms and NCI among PWH with well-controlled infection.

Methods: The Neurocognitive Assessment in the Metabolic and Ageing Cohort study is an ongoing, prospective, longitudinal study of PWH aged ≥45 years old nested within the Swiss HIV Cohort Study. Neurocognitive Assessment in the Metabolic and Ageing Cohort study participants underwent neurocognitive assessment and grading of depressive symptoms using the Centre for Epidemiological Studies Depression Scale. Neurocognitive impairment categories were defined using Frascati criteria. Participants with NCI related to neurological or psychiatric confounders other than depression were excluded. The cross-sectional association between the Centre for Epidemiological Studies Depression score and neurocognitive impairment was examined taking Centre for Epidemiological Studies Depression score as a continuous variable and then as a binary variable using two score thresholds, 16 and 27.

Results: Excluding 79 participants with confounding factors, 902 participants were studied: 81% were men; 96% had plasma viral loads <50 copies/ml; 35% had neurocognitive impairment; 28% had Centre for Epidemiological Studies Depression scores ≥16. Higher Centre for Epidemiological Studies Depression scores were associated with female sex ( = 0.0003), non-Caucasian origin ( = 0.011) and current/past intravenous drug use ( = 0.002). Whilst neurocognitive impairment was associated with higher Centre for Epidemiological Studies Depression scores, the Centre for Epidemiological Studies Depression score was a poor predictor of having neurocognitive impairment (area under the ROC curve 0.604). Applying a Centre for Epidemiological Studies Depression score threshold of 16 predicted the presence of neurocognitive impairment with a sensitivity of 38.3% (specificity 77.2%), increasing the threshold to 27 lowered sensitivity to 15.4% (specificity 93.6%).

Conclusion: In this large cohort of PWH in Switzerland, we did not observe a Centre for Epidemiological Studies Depression score threshold that was sensitive in predicting neurocognitive impairment. As neurocognitive impairment was however associated with higher Centre for Epidemiological Studies Depression scores, the data support the screening for and treatment of depression among PWH diagnosed with neurocognitive impairment.
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http://dx.doi.org/10.1177/0956462420987434DOI Listing
February 2021

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Nat Commun 2021 02 22;12(1):1219. Epub 2021 Feb 22.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.
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http://dx.doi.org/10.1038/s41467-021-21485-wDOI Listing
February 2021

Association of Incomplete Adherence to Antiretroviral Therapy With Cardiovascular Events and Mortality in Virologically Suppressed Persons With HIV: The Swiss HIV Cohort Study.

Open Forum Infect Dis 2021 Feb 21;8(2):ofab032. Epub 2021 Jan 21.

University of Basel, Basel, Switzerland.

Background: Incomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, its clinical implications remain unknown.

Methods: PWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression (<50 copies/mL) for ≥6 months were evaluated. The association between incomplete self-reported ART adherence (≥1 or ≥2 missed doses in the last month) and (1) any CVD event (myocardial infarction, revascularization, cerebral hemorrhage, stroke, and/or death due to CVD event) or (2) non-CVD-related death was evaluated using adjusted Cox proportional hazards models.

Results: A total of 6971 PWH (74% male) were included in the analysis (median age [interquartile range {IQR}], 39 [32-47] years). The median (IQR) follow-up was 8 (4-11) years, with 14 (8-23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing ≥1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio [HR], 1.23; 95% CI, 0.85-1.79;  = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing ≥1 ART dose (HR, 1.44; 95% CI, 1.00-2.07;  = .05) and missing ≥2 ART doses (HR, 2.21; 95% CI, 1.37-3.57;  = .001).

Conclusions: Incomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes.
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http://dx.doi.org/10.1093/ofid/ofab032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880264PMC
February 2021

Prophylaxis for COVID-19: a systematic review.

Clin Microbiol Infect 2021 Jan 18. Epub 2021 Jan 18.

HIV/AIDS Unit, Department of Infectious Diseases, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Background: While the landscape of vaccine and treatment candidates against the novel coronavirus disease 2019 (COVID-19) has been reviewed systematically, prophylactic candidates remain unexplored.

Objectives: To map pre- and postexposure prophylactic (PrEP and PEP) candidate for COVID-19.

Data Sources: PubMed/Medline, Embase, International Committee of Medical Journal Editors and International Clinical Trials Registry Platform clinical trial registries and medRxiv.

Study Eligibility Criteria And Participants: All studies in humans or animals and randomized controlled trials (RCTs) in humans reporting primary data on prophylactic candidates against COVID-19, excluding studies focused on key populations.

Interventions: PrEP and PEP candidate for COVID-19.

Methods: Systematic review and qualitative synthesis of COVID-19 PrEP and PEP studies and RCTs complemented by search of medRxiv and PubMed and Embase for studies reporting RCT outcomes since systematic review search completion.

Results: We identified 13 studies (from 2119 database records) and 117 RCTs (from 5565 RCTs listed in the registries) that met the inclusion criteria. Non-RCT studies reported on cross-sectional studies using hydroxychloroquine (HCQ) in humans (n = 2) or reported on animal studies (n = 7), most of which used antibodies. All five completed RCTs focused on the use of HCQ as either PrEP or PEP, and these and the cross-sectional studies reported no prophylactic effect. The majority of ongoing RCTs evaluated HCQ or other existing candidates including non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, anti(retro)virals or use of vitamins and supplements.

Conclusions: The key message from completed studies and RCTs seems to be that HCQ does not work. There is little evidence regarding other compounds, with all RCTs using candidates other than HCQ still ongoing. It remains to be seen if the portfolio of existing molecules being evaluated in RCTs will identify successful prophylaxis against COVID-19 or if there is a need for the development of new candidates.
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http://dx.doi.org/10.1016/j.cmi.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813508PMC
January 2021

The Impact of Binge Drinking on Mortality and Liver Disease in the Swiss HIV Cohort Study.

J Clin Med 2021 Jan 14;10(2). Epub 2021 Jan 14.

Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.

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.
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http://dx.doi.org/10.3390/jcm10020295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830571PMC
January 2021

[HIV in the time of COVID-19 : the meeting between two pandemics].

Rev Med Suisse 2021 Jan;17(720-1):95-101

Service des maladies infectieuses, CHUV, 1011 Lausanne.

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.
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January 2021

Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

Swiss Med Wkly 2020 12 31;150:w20446. Epub 2020 Dec 31.

Division of Prison Health, University of Geneva and University Hospitals of Geneva, Thônex, Switzerland / Office of Corrections, Department of Justice and Home Affairs of the Canton of Zurich, Zurich, Switzerland.

Aims Of The Study: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19).

Methods: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs.

Results: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619).

Conclusions: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.
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http://dx.doi.org/10.4414/smw.2020.20446DOI Listing
December 2020

Cyber harassment of female scientists will not be the new norm.

Lancet Infect Dis 2020 Dec 23. Epub 2020 Dec 23.

HIV Unit, Infectious Diseases Division, Geneva University Hospitals, Switzerland; Faculty of Medicine, University of Geneva, Switzerland.

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http://dx.doi.org/10.1016/S1473-3099(20)30944-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758174PMC
December 2020

Clinical outcomes of two-drug regimens vs. three-drug regimens in antiretroviral treatment-experienced people living with HIV.

Clin Infect Dis 2020 Dec 23. Epub 2020 Dec 23.

Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK.

Background: Limited data exist comparing clinical outcomes of two-drug regimens (2DRs) and three-drug regimens (3DRs) in people living with HIV.

Methods: Antiretroviral treatment-experienced individuals in RESPOND switching to a new 2DR or 3DR from 1/1/12-1/10/18 were included. The incidence of clinical events (AIDS, non-AIDS cancer, cardiovascular disease, end-stage liver and renal disease, death) was compared between regimens using Poisson regression.

Results: Of 9791 individuals included, 1088 (11.1%) started 2DRs and 8703 (88.9%) 3DRs. The most common 2DRs were dolutegravir plus lamivudine (22.8%) and raltegravir plus boosted darunavir (19.8%); the most common 3DR was dolutegravir plus 2 nucleoside reverse transcriptase inhibitors (46.9%). Individuals on 2DRs were older (median 52.6 years [interquartile range 46.7-59.0] vs 47.7 [39.7-54.3]), and a higher proportion had ≥1 comorbidity (81.6% vs 73.9%).There were 619 events during 27,159 person-years of follow-up (PYFU): 540 (incidence rate [IR] 22.5/1000 PYFU [95% CI 20.7-24.5]) on 3DRs, 79 (30.9/1000 PYFU [24.8-38.5]) on 2DRs. The most common events were death (7.5/1000 PYFU [95% CI 6.5-8.6]) and non-AIDS cancer (5.8/1000 PYFU [4.9-6.8]). After adjustment for baseline demographic and clinical characteristics, there was a similar incidence of events on both regimen types (2DRs vs 3DRs IR ratio: 0.92 [0.72-1.19]; p=0.53).

Conclusions: This is the first large, international cohort assessing clinical outcomes on 2DRs. After accounting for baseline characteristics, there was a similar incidence of events on 2DRs and 3DRs. 2DRs appear to be a viable treatment option with regard to clinical outcomes; further research on resistance barriers and long-term durability of 2DRs is needed.
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http://dx.doi.org/10.1093/cid/ciaa1878DOI Listing
December 2020

Rosuvastatin therapy in people with HIV at intermediate cardiovascular risk does not decrease biomarkers of inflammation and immune activation.

J Infect Dis 2020 Dec 22. Epub 2020 Dec 22.

Life Sciences Discipline, Burnet Institute, Melbourne, Victoria, Australia.

Background: Statins may help prevent cardiovascular disease (CVD) in people with HIV (PWH) with chronic inflammation due to their pleotropic lipid lowering and anti-inflammatory properties.

Methods: The impact of 48 weeks of rosuvastatin therapy on inflammation and immune activation in a double-blind, placebo-controlled trial in PWH at moderate CVD risk was assessed.

Results: Rosuvastatin not alter plasma levels of IL-6, soluble (s)TNF-RII, CXCL10, sCD14 or sVCAM-1 (p≥0.1 for all). Proportions of CD16 + monocyte subsets were increased in PWH receiving rosuvastatin.

Conclusions: The potential benefits of statin use in PWH with normal lipid levels requires further clinical outcome research.
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http://dx.doi.org/10.1093/infdis/jiaa775DOI Listing
December 2020

Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis.

EClinicalMedicine 2020 Nov 16;28:100573. Epub 2020 Oct 16.

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: To inform World Health Organization (WHO) global guidelines, we updated and expanded the evidence base to assess the comparative efficacy, tolerability, and safety of first-line antiretroviral therapy (ART) regimens.

Methods: We searched Embase, Medline and CENTRAL on 28 February 2020 to update the systematic literature review of clinical trials comparing recommended first-line ART that informed previous WHO guidelines. Outcomes included viral suppression, change in CD4 cell counts, mortality, serious and overall adverse events (AEs), discontinuation, discontinuations due to AEs (DAEs); and new outcomes: drug-resistance, neuropsychiatric AEs, early viral suppression, weight gain and birth outcomes. Comparative effects were assessed through network meta-analyses and certainty in the evidence was assessed using the GRADE framework.

Findings: We identified 156 publications pertaining to 68 trials for the primary population. Relative to efavirenz, dolutegravir had improved odds of viral suppression across all time points (odds ratio [OR]: 1·94; 95% credible interval [CrI]: 1·48-2·56 at 96 weeks); was protective of drug-resistance (OR: 0·13; 95%CrI: 0·04-0·48); and led to fewer discontinuations (OR: 0·58; 95%CrI: 0·48-0·70). Evidence supported dolutegravir use among TB-HIV co-infected persons and pregnant women. Adverse birth outcomes were observed in 33.2% of dolutegravir-managed pregnancies and 35.0% of efavirenz-managed pregnancies. Low-dose efavirenz had comparable efficacy and safety to standard-dose efavirenz, but led to fewer DAEs (OR: 0·70; 95%CrI: 0·50-0·92).

Interpretation: The evidence supports choosing dolutegravir in combination with lamivudine/emtricitabine and tenofovir disoproxil fumarate as the preferred first-line regimen and low-dose efavirenz-based regimens as an alternative. Dolutegravir can be considered to be effective, safe and tolerable.

Funding: WHO.
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http://dx.doi.org/10.1016/j.eclinm.2020.100573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700905PMC
November 2020

Analysis of inappropriate prescribing in elderly patients of the Swiss HIV Cohort Study reveals gender inequity.

J Antimicrob Chemother 2021 Feb;76(3):758-764

University of Basel, Basel, Switzerland.

Background: The extent of inappropriate prescribing observed in geriatric medicine has not been thoroughly evaluated in people ageing with HIV. We determined the prevalence of and risk factors for inappropriate prescribing in individuals aged ≥75 years enrolled in the Swiss HIV Cohort Study.

Methods: Retrospective review of medical records was performed to gain more insights into non-HIV comorbidities. Inappropriate prescribing was screened using the Beers criteria, the STOPP/START criteria and the Liverpool drug-drug interactions (DDIs) database.

Results: For 175 included individuals, the median age was 78 years (IQR 76-81) and 71% were male. The median number of non-HIV comorbidities was 7 (IQR 5-10). The prevalence of polypharmacy and inappropriate prescribing was 66% and 67%, respectively. Overall, 40% of prescribing issues could have deleterious consequences. Prescribing issues occurred mainly with non-HIV drugs and included: incorrect dosage (26%); lack of indication (21%); prescription omission (drug not prescribed although indicated) (17%); drug not appropriate in elderly individuals (18%) and deleterious DDIs (17%). In the multivariable logistic regression, risk factors for prescribing issues were polypharmacy (OR: 2.5; 95% CI: 1.3-4.7), renal impairment (OR: 2.7; 95% CI: 1.4-5.1), treatment with CNS-active drugs (OR: 2.1; 95% CI: 1.1-3.8) and female sex (OR: 8.3; 95% CI: 2.4-28.1).

Conclusions: Polypharmacy and inappropriate prescribing are highly prevalent in elderly people living with HIV. Women are at higher risk than men, partly explained by sex differences in the occurrence of non-HIV comorbidities and medical care. Medication reconciliation and periodic review of prescriptions by experienced physicians could help reduce polypharmacy and inappropriate prescribing in this vulnerable, growing population.
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http://dx.doi.org/10.1093/jac/dkaa505DOI Listing
February 2021

Caring for people living with HIV during the global coronavirus disease 2019 pandemic.

AIDS 2021 03;35(3):355-358

HIV/AIDS Unit, Division of Infectious Diseases, Geneva University Hospitals.

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http://dx.doi.org/10.1097/QAD.0000000000002775DOI Listing
March 2021

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

AIDS 2021 Mar;35(4):619-624

Division of Infectious Diseases, HIV/AIDS Unit, Geneva University Hospitals, Geneva, Switzerland.

Background: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease.

Objective: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population.

Design: A double-blind multicentre, randomised, placebo-controlled trial was performed.

Methods: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357).

Results: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011].

Conclusion: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.
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http://dx.doi.org/10.1097/QAD.0000000000002764DOI Listing
March 2021

[Buyers' club : an alternative for access to treatment ?]

Rev Med Suisse 2020 Nov;16(715):2228-2231

Direction médicale et qualité, HUG, 1211 Genève 14.

Rapid medication management for patients infected with HIV, HCV or HBV is key in optimizing a more favourable clinical response, in terms of morbidity, mortality, quality-of-life and reduced risk of transmission. If a drug is expensive, access to treatment for an uninsured patient with limited resources can be a hurdle that leads to forgoing healthcare for economic reasons. The buyers' club's objective is to provide logistics and/or financial assistance to a patient aiming to import qualitative generics for his personal use at an affordable price oversea. The drug is purchased on the internet.
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November 2020

Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial.

BMJ Open 2020 11 12;10(11):e040110. Epub 2020 Nov 12.

HIV Unit, Geneva University Hospitals, Geneva, Switzerland.

Introduction: Lopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.

Methods And Analysis: COPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.

Ethics And Dissemination: Ethics approval has been granted by the Commission Cantonale d'Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.

Trial Registration Number: Clinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).

Registered Report Identifier: CCER 2020-0864.
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http://dx.doi.org/10.1136/bmjopen-2020-040110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662450PMC
November 2020

Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL'HIV trial.

PLoS Med 2020 11 10;17(11):e1003421. Epub 2020 Nov 10.

HIV/AIDS Unit, Department of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.

Background: Dolutegravir (DTG)-based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL'HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART.

Methods And Findings: SIMPL'HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel-Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than -12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference -1.2%; 95% CI -7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI -5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference -1.1%; 95% CI -9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study's main limitations included a rather small proportion of women included, the open label design, and its short duration.

Conclusions: In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals.

Trial Registration: ClinicalTrials.gov NCT03160105.
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http://dx.doi.org/10.1371/journal.pmed.1003421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654764PMC
November 2020

Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART.

Nat Commun 2020 11 2;11(1):5542. Epub 2020 Nov 2.

Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients' hurdle towards a cure.
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http://dx.doi.org/10.1038/s41467-020-19198-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608612PMC
November 2020

Longitudinal Progression of Subclinical Coronary Atherosclerosis in Swiss HIV-Positive Compared With HIV-Negative Persons Undergoing Coronary Calcium Score Scan and CT Angiography.

Open Forum Infect Dis 2020 Oct 16;7(10):ofaa438. Epub 2020 Sep 16.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: People with HIV (HIV+) may have increased cardiovascular event rates compared with HIV-negative (HIV-) persons. Cross-sectional data from the United States and Switzerland, based on coronary artery calcium scan (CAC) and coronary computed tomography angiography (CCTA), suggest, respectively, increased and similar prevalence of subclinical atherosclerosis in HIV+ vs HIV- persons.

Methods: We repeated CAC/CCTA in 340 HIV+ and 90 HIV- study participants >2 years after baseline CAC/CCTA. We assessed the association of HIV infection, Framingham risk score (FRS), and HIV-related factors with the progression of subclinical atherosclerosis.

Results: HIV+ were younger than HIV- participants (median age, 52 vs 56 years;  < .01) but had similar median 10-year FRS (8.9% vs 9.0%;  = .82); 94% had suppressed HIV viral load. In univariable and multivariable analyses, FRS was associated with the incidence rate ratio (IRR) of new subclinical atherosclerosis at the follow-up CAC/CCTA, but HIV infection was not: any plaque (adjusted IRR for HIV+ vs HIV- participants, 1.21; 95% CI, 0.62-2.35), calcified plaque (adjusted IRR for HIV+ vs HIV- participants, 1.06; 95% CI, 0.56-2), noncalcified/mixed plaque (adjusted IRR for HIV+ vs HIV- participants, 1.24; 95% CI, 0.69-2.21), and high-risk plaque (adjusted IRR for HIV+ vs HIV- participants, 1.46; 95% CI, 0.66-3.20). Progression of CAC score between baseline and follow-up CAC/CCTA was similar in HIV+ (median annualized change [interquartile range {IQR}], 0.41 [0-10.19]) and HIV- participants (median annualized change [IQR], 2.38 [0-16.29];  = .11), as was progression of coronary segment severity score (HIV+: median annualized change [IQR], 0 [0-0.47]; HIV-: median annualized change [IQR], 0 [0-0.52];  = .10) and coronary segment involvement score (HIV+: median annualized change [IQR], 0 [0-0.45]; HIV-: median annualized change [IQR], 0 [0-0.41];  = .25).

Conclusions: In this longitudinal CAC/CCTA study from Switzerland, Framingham risk score was associated with progression of subclinical atherosclerosis, but HIV infection was not.
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http://dx.doi.org/10.1093/ofid/ofaa438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585327PMC
October 2020

Predictors of virological failure and time to viral suppression of first line integrase inhibitor based antiretroviral treatment.

Clin Infect Dis 2020 Oct 24. Epub 2020 Oct 24.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Background: Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of HIV-infection. We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens.

Methods: We studied time to treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study.We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS defining events and the type of InSTI.In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.

Results: We observed 121 virological failures during 18'447 person-years of follow-up. A baseline viral load ≥100'000 cps/mL (multivariable Hazard Ratio (mHR): 2.2, 95% CI: 1.3-3.6) and an AIDS defining event (mHR: 1.8, 95% CI: 1.1-3.0) were associated with treatment failure. CD4 counts between 200-500 cells/µL (mHR: 0.5, 95% CI: 0.3-0.8) and >500 cells/µL (mHR: 0.4, 95% CI: 0.2-0.7) were protective. Median [IQR] time to viral suppression was 50 [29,107] days. Time to suppression was shorter in lower viral load strata (mHR: 0.7, 95% CI: 0.6-0.8) and in dolutegravir-based therapy (mHR: 1.2, 95% CI: 1.0-1.4). Minor resistance mutations were found at baseline in 104/646 (16%) patients with no effect on treatment outcome.

Conclusion: Among drug-naïve HIV-infected individuals treated with InSTI-based regimens, factors associated with treatment failure, in particular high viral load and low CD4 counts remain similar to older treatments. Minor InSTI resistance mutations had no impact in this large observational cohort.
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http://dx.doi.org/10.1093/cid/ciaa1614DOI Listing
October 2020

Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon.

Lancet HIV 2020 10;7(10):e677-e687

TransVIHMI, University of Montpellier, IRD, INSERM, 34394 Montpellier, France; Montpellier University Hospital Centre, Montpellier, France.

Background: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96.

Methods: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing.

Findings: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p<0·001). Virological failure (>1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p<0·001, and incidence of obesity, 22% in the dolutegravir group and 16% in the efavirenz 400 mg group, p=0·043). The incidence of new WHO HIV-related stage 3 and 4 events was similar in each group (12 [4%] in each group). The two groups had similar rates of serious adverse events (28 [9%] of 310 in the dolutegravir group and 21 [7%] of 303 in the efavirenz 400 mg group). 18 deaths were observed during the 96-week follow-up (eight in the dolutegravir group and ten in the efavirenz 400 mg group).

Interpretation: The non-inferior efficacy of the dolutegravir-based regimen and non-emergence of dolutegravir resistance at 96 weeks supports its use as a first-line regimen for antiretroviral-naive adults with HIV-1 infection. Viral load suppression was reached more quickly in the dolutegravir group and weight gain was significantly higher.

Funding: UNITAID and the French National Agency for AIDS Research.
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http://dx.doi.org/10.1016/S2352-3018(20)30238-1DOI Listing
October 2020

disseminated infection in an immunocompetent patient without predisposing factors.

BMJ Case Rep 2020 Sep 29;13(9). Epub 2020 Sep 29.

Division of Pulmonology, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.

Most infections described involve direct inoculation through skin lesions. We describe the case of a patient without risk factors who presented with an intracranial mass and a pulmonary infection with As are rarely pathogens, there is little knowledge about the optimal treatment and outcome of such infections: what is the best mode of administration, what is the best therapy duration and is surgery always required are some of the unanswered questions. In our patient, surgical removal of the mass associated with a 1-year antimycobacterial therapy led to a full recovery. Even though was rapidly identified in sputum, it was initially considered non-pathogenic and the definitive diagnosis required almost 6 weeks of investigations. New molecular techniques will probably lead to more identifications of in the next few years and a better knowledge of their possible pathogenicity and optimal treatment.
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http://dx.doi.org/10.1136/bcr-2020-235842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526288PMC
September 2020

Macrophage activation syndrome as an unusual presentation of paucisymptomatic severe acute respiratory syndrome coronavirus 2 infection: A case report.

Medicine (Baltimore) 2020 Aug;99(32):e21570

Division of General Internal Medicine, Department of Medicine.

Rationale: Macrophage activation syndrome (MAS) is a rare life-threatening condition characterized by cytokine-mediated tissue injury and multiorgan dysfunction.

Patient Concerns: We describe the unique case of young man who developed MAS as the sole manifestation of an otherwise paucisymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Diagnoses: Clinical and biological criteria led to the diagnosis of MAS; cytokine profile was highly suggestive reverse transcription polymerase chain reaction for SARS-CoV-2 in nasopharyngeal swabs was negative, but serum anti-SARS-CoV-2 immunoglobulin A and immunoglobulin G resulted positive leading to the diagnosis of SARS-CoV-2 infection.

Interventions: The patient was treated with empiric antibiotic and hydroxychloroquine.

Outcomes: Clinical improvement ensued. At follow-up, the patient is well.

Lesson: SARS-CoV-2 infection may trigger develop life-threatening complications, like MAS. This can be independent from coronavirus disease 2019 gravity.
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http://dx.doi.org/10.1097/MD.0000000000021570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593078PMC
August 2020

Telomere Length, Traditional Risk Factors, HIV-related Factors and Coronary Artery Disease Events in Swiss Persons Living with HIV.

Clin Infect Dis 2020 Jul 29. Epub 2020 Jul 29.

University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.

Background: Leukocyte telomere length (TL) shortens with age and is associated with coronary artery disease (CAD) events in the general population. Persons living with HIV (PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH.

Methods: We measured TL by quantitative PCR in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 01.01.2000-31.12.2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses.

Results: We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR=0.56 (95% confidence interval, 0.35-0.91) and OR=0.54 (0.31-0.96). Multivariable OR for current smoking was 1.93 (1.27-2.92), dyslipidemia OR=1.92 (1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR=1.82 (1.27-2.59), OR=2.02 (1.34-3.04), OR=3.42 (2.14-5.45), and OR=1.66 (1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use.

Conclusion: In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.
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http://dx.doi.org/10.1093/cid/ciaa1034DOI Listing
July 2020

Prevalence of potential drug-drug interactions in patients of the Swiss HIV Cohort Study in the era of HIV integrase inhibitors.

Clin Infect Dis 2020 Jul 8. Epub 2020 Jul 8.

Division of Infectious Diseases & Hospital Hygiene, University Hospital Basel and University of Basel, Basel, Switzerland.

Background: Prevalence of potential drug-drug interactions (PDDIs) between antiretroviral drugs (ARVs) and comedications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of HIV integrase inhibitors (INIs), characterized by more favorable interaction profiles.

Methods: The prevalence of PDDIs in treated HIV positive individuals was assessed for the period: 01-12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged) or of weak clinical significance (yellow flagged).

Results: In 9'298 included individuals, median age was 51 years (IQR 43; 58), and 72% were males. Individuals received unboosted INIs (40%), boosted ARVs (30%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (32%) based regimens. In the entire cohort, 68% received > 1 comedication, 14% had polypharmacy (> 5 comedications) and 29% had > 1 PDDI. Among individuals with comedication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber - mostly with cardiovascular drugs - and 20% yellow flagged PDDIs) compared to 59% in 2008. Two percent had red flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared to 2008, fewer individuals received boosted ARVs (-24%) and NNRTIs (-13%) but the use of comedications was higher.

Conclusions: Prevalence of PDDIs was lower with more widespread use of INIs in 2018 than in 2008. Continued use of boosted regimens and increasing needs for comedications in this aging population impeded lower rates of PDDIs.
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http://dx.doi.org/10.1093/cid/ciaa918DOI Listing
July 2020

Author Correction: HIV and antiretroviral therapy-related fat alterations.

Nat Rev Dis Primers 2020 07 2;6(1):54. Epub 2020 Jul 2.

Sorbonne Université, Faculty of Medicine, Inserm UMR_S938, Saint- Antoine Research Centre, FRM EQU201903007868, ICAN, RHU CARMMA, Paris, France.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41572-020-0197-6DOI Listing
July 2020

Clinicopathologic Aspects of a Papulovesicular Eruption in a Patient With COVID-19.

JAMA Dermatol 2020 08;156(8):922-924

Department of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.

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http://dx.doi.org/10.1001/jamadermatol.2020.1966DOI Listing
August 2020

HIV and antiretroviral therapy-related fat alterations.

Nat Rev Dis Primers 2020 06 18;6(1):48. Epub 2020 Jun 18.

Sorbonne Université, Faculty of Medicine, Inserm UMR_S938, Saint-Antoine Research Centre, FRM EQU201903007868, ICAN, RHU CARMMA, Paris, France.

Early in the HIV epidemic, lipodystrophy, characterized by subcutaneous fat loss (lipoatrophy), with or without central fat accumulation (lipohypertrophy), was recognized as a frequent condition among people living with HIV (PLWH) receiving combination antiretroviral therapy. The subsequent identification of thymidine analogue nucleoside reverse transcriptase inhibitors as the cause of lipoatrophy led to the development of newer antiretroviral agents; however, studies have demonstrated continued abnormalities in fat and/or lipid storage in PLWH treated with newer drugs (including integrase inhibitor-based regimens), with fat gain due to restoration to health in antiretroviral therapy-naive PLWH, which is compounded by the rising rates of obesity. The mechanisms of fat alterations in PLWH are complex, multifactorial and not fully understood, although they are known to result in part from the direct effects of HIV proteins and antiretroviral agents on adipocyte health, genetic factors, increased microbial translocation, changes in the adaptive immune milieu after infection, increased tissue inflammation and accelerated fibrosis. Management includes classical lifestyle alterations with a role for pharmacological therapies and surgery in some patients. Continued fat alterations in PLWH will have an important effect on lifespan, healthspan and quality of life as patients age worldwide, highlighting the need to investigate the critical uncertainties regarding pathophysiology, risk factors and management.
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http://dx.doi.org/10.1038/s41572-020-0181-1DOI Listing
June 2020

Cohort-derived machine learning models for individual prediction of chronic kidney disease in people living with HIV: a prospective multicentre cohort study.

J Infect Dis 2020 May 9. Epub 2020 May 9.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: It is unclear whether data-driven machine learning models, which are trained on large epidemiological cohorts, may improve prediction of co-morbidities in people living with HIV.

Methods: In this proof-of-concept study, we included people living with HIV of the prospective Swiss HIV Cohort Study with a first estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 after January 1, 2002. Our primary outcome was chronic kidney disease (CKD) ─ defined as confirmed decrease in eGFR ≤60 ml/min/1.73 m2 over three months apart. We split the cohort data into a training set (80%), validation set (10%), and test set (10%) ─ stratified for CKD status and follow-up length.

Results: Of 12,761 eligible individuals (median baseline eGFR, 103 ml/min/1.73 m2), 1,192 (9%) developed a CKD after a median of eight years. We used 64 static and 502 time-changing variables: Across prediction horizons and algorithms and in contrast to expert-based standard models, most machine learning models achieved state-of-the-art predictive performances with areas under the receiver operating characteristic curve and precision recall curve ranging from 0.926 to 0.996 and from 0.631 to 0.956, respectively.

Conclusions: In people living with HIV, we observed state-of-the-art performances in forecasting individual CKD onsets with different machine learning algorithms.
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http://dx.doi.org/10.1093/infdis/jiaa236DOI Listing
May 2020

Possible link between anosmia and COVID-19: sniffing out the truth.

Eur Arch Otorhinolaryngol 2020 07 17;277(7):2149-2150. Epub 2020 Apr 17.

Division of Infectious Diseases, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211, Geneva 14, Switzerland.

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http://dx.doi.org/10.1007/s00405-020-05966-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164410PMC
July 2020