Publications by authors named "Katharine E A Darling"

25 Publications

  • Page 1 of 1

Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.

PLoS One 2021 2;16(3):e0246579. Epub 2021 Mar 2.

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

Background: Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.

Results: Most participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function.

Conclusions: In this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924787PMC
March 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

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

[Stigma and HIV: relevant for everyone].

Rev Med Suisse 2020 Apr;16(690):744-748

Consultation ambulatoire des maladies infectieuses, Service des maladies infectieuses, CHUV, 1011 Lausanne.

Medical advances in the treatment of HIV over the last 35 years mean that people living with HIV (PLHIV) now have a life expectancy close to that of the general population. Further, when successfully treated, PLHIV cannot transmit the virus. Despite this, HIV-related stigma remains widespread, including within healthcare settings. Stigma is not a vague sociological notion but represents a real threat to public health, with repercussions for both PLHIV and HIV-negative individuals. Stigma has been shown to have a negative impact on HIV prevention, testing, access to health services, and on the healthcare management of PLHIV. Taking stigma into consideration is essential, both in meeting the medical and psycho-social needs of PLHIV and in order to effectively combat HIV/AIDS.
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April 2020

Antibodies against HPV16E6 oncoprotein in the Swiss HIV cohort study: Kinetics and anal cancer risk prediction.

Int J Cancer 2020 08 4;147(3):757-765. Epub 2019 Dec 4.

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

Our aim was to describe HPV16E6 antibody kinetics prior to anal cancer in people living with HIV/AIDS (PLWHA) and evaluate the possible contribution of HPV16E6 serology to anal cancer risk prediction. For 91 persons diagnosed with anal cancer in the Swiss HIV Cohort Study (1989-2017), serial serum/plasma samples were tested for HPV16E6 antibodies using multiplex serology, supplemented with samples from 1,356 participants without anal cancer. Anal cancer incidence was estimated for PLWHA from 40 years-old in the cART era, stratified by HPV16E6 serostatus. HPV16E6 seroprevalence was 23.3% in samples <2 years prior to anal cancer diagnosis and decreased with increasing time prior to cancer: 16.7% at 2-4 years, 4.4% at 5-9, and 7.0% at ≥10 years. Of 25 individuals with anal cancer who were HPV16E6-seropositive at any time during follow-up, the majority (n = 18) remained seropositive in all samples after seroconversion, whereas for seven cases, seropositivity was transitory. Among individuals with anal cancer, HPV16E6 seroprevalence was marginally higher in women vs. men who have sex with men (adjusted OR = 4.3, 95% CI: 1.1, 17.2) and in older participants (adjusted OR = 6.2, 95% CI: 1.1, 34.8 for cases diagnosed at ≥55 vs. <45 years). Anal cancer incidence was 402/100,000 person-years in HPV16E6-positive vs. 82/100,000 in HPV16E6-negative PLWHA (incidence rate ratio = 4.9, 95% CI: 1.3, 13.1). In conclusion, HPV16E6 serology, despite its low sensitivity, allows characterization of a group of individuals with very high anal cancer incidence and may have a place in secondary prevention in groups at high risk for anal cancer such as PLWHA.
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http://dx.doi.org/10.1002/ijc.32784DOI Listing
August 2020

Cross-Sectional and Cumulative Longitudinal Central Nervous System Penetration Effectiveness Scores Are Not Associated With Neurocognitive Impairment in a Well Treated Aging Human Immunodeficiency Virus-Positive Population in Switzerland.

Open Forum Infect Dis 2019 Jul 8;6(7):ofz277. Epub 2019 Jul 8.

Infectious Diseases Service, Lausanne University Hospital, Switzerland.

Background: Neurocognitive impairment (NCI) in people with human immunodeficiency virus (PWH) remains a concern despite potent antiretroviral therapy (ART). Higher central nervous system (CNS) penetration effectiveness (CPE) scores have been associated with better CNS human immunodeficiency virus (HIV) replication control, but the association between CPE and NCI remains controversial.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a subgroup of the Swiss HIV Cohort Study (SHCS) that invited patients aged ≥45 years enrolled in the SHCS and followed-up at NAMACO-affiliated centers in Switzerland to participate between May 2013 and November 2016. In total, 981 patients were enrolled, all of whom underwent standardized neurocognitive assessment. Neurocognitive impairment, if present, was characterized using Frascati criteria. The CPE scores of NAMACO study participants with undetectable plasma HIV-ribonucleic acid at enrollment (909 patients) were analyzed. Cross-sectional CPE scores (at neurocognitive assessment) were examined as potential predictors of NCI in multivariate logistic regression models. The analysis was then repeated taking CPE as a cumulative score (summarizing CPE scores from ART initiation to the time of neurocognitive assessment).

Results: Most patients were male (80%) and Caucasian (92%). Neurocognitive impairment was present in 40%: 27% with HIV-associated NCI (mostly asymptomatic neurocognitive impairment), and 13% with NCI related to other factors. None of the CPE scores, neither cross-sectional nor cumulative, was statistically significantly associated with NCI.

Conclusions: In this large cohort of aviremic PWH, we observed no association between NCI, whether HIV-associated or related to other factors, and CPE score, whether cross-sectional or cumulative.
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http://dx.doi.org/10.1093/ofid/ofz277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612860PMC
July 2019

Cross-Sectional and Cumulative Longitudinal Central Nervous System Penetration Effectiveness Scores Are Not Associated With Neurocognitive Impairment in a Well Treated Aging Human Immunodeficiency Virus-Positive Population in Switzerland.

Open Forum Infect Dis 2019 Jul 8;6(7):ofz277. Epub 2019 Jul 8.

Infectious Diseases Service, Lausanne University Hospital, Switzerland.

Background: Neurocognitive impairment (NCI) in people with human immunodeficiency virus (PWH) remains a concern despite potent antiretroviral therapy (ART). Higher central nervous system (CNS) penetration effectiveness (CPE) scores have been associated with better CNS human immunodeficiency virus (HIV) replication control, but the association between CPE and NCI remains controversial.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a subgroup of the Swiss HIV Cohort Study (SHCS) that invited patients aged ≥45 years enrolled in the SHCS and followed-up at NAMACO-affiliated centers in Switzerland to participate between May 2013 and November 2016. In total, 981 patients were enrolled, all of whom underwent standardized neurocognitive assessment. Neurocognitive impairment, if present, was characterized using Frascati criteria. The CPE scores of NAMACO study participants with undetectable plasma HIV-ribonucleic acid at enrollment (909 patients) were analyzed. Cross-sectional CPE scores (at neurocognitive assessment) were examined as potential predictors of NCI in multivariate logistic regression models. The analysis was then repeated taking CPE as a cumulative score (summarizing CPE scores from ART initiation to the time of neurocognitive assessment).

Results: Most patients were male (80%) and Caucasian (92%). Neurocognitive impairment was present in 40%: 27% with HIV-associated NCI (mostly asymptomatic neurocognitive impairment), and 13% with NCI related to other factors. None of the CPE scores, neither cross-sectional nor cumulative, was statistically significantly associated with NCI.

Conclusions: In this large cohort of aviremic PWH, we observed no association between NCI, whether HIV-associated or related to other factors, and CPE score, whether cross-sectional or cumulative.
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http://dx.doi.org/10.1093/ofid/ofz277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612860PMC
July 2019

Targeted versus non-targeted HIV testing offered via electronic questionnaire in a Swiss emergency department: A randomized controlled study.

PLoS One 2018 7;13(3):e0190767. Epub 2018 Mar 7.

Emergency Department, Lausanne University Hospital, Lausanne, Switzerland.

Background: In Switzerland, the national HIV testing recommendations propose targeted testing. Although the emergency department (ED) is mentioned specifically as a site where HIV testing should take place, the testing rate in our ED is 1% of patients seen. The aim of this study was to use electronic tablets to offer testing to ED patients and to examine whether non-targeted screening increased testing rates compared to targeted testing.

Methods: This randomised, cross-over design study took place at Lausanne University Hospital, Switzerland, between August and November 2015. Eligible patients were randomised to a targeted testing or a non-targeted screening arm. Using electronic tablets, targeted arm patients completed a risk factor assessment; patients with risk factors were offered free rapid HIV testing. Non-targeted arm patients received information about HIV and HIV testing on their tablet and were then offered testing. In a second step, patients who declined testing were crossed over to the other strategy. The primary endpoint was the HIV testing rate per arm.

Results: Eighty patients were recruited to each study arm. In the targeted arm, 17 patients (of 80, 21%) had at least one risk factor and were offered testing, of whom eight (of 17, 47%) accepted. HIV testing rate in the targeted arm was 10% (8/80) compared to 48% (38/80) in the non-targeted arm (P<0.001). Secondary cross-screening, where targeted arm patients without risk factors were offered non-targeted screening, increased the testing rate in the targeted arm to 45% (36/80). Among patients offered testing, the acceptance rate did not differ between targeted and non-targeted arms, at 48% and 53%, respectively (P = 0.9).

Discussion: In our centre, non-targeted HIV screening resulted in a higher testing rate than targeted testing due to more patients being offered a test. The acceptance rate of testing offered did not differ between targeted and non-targeted arms. Electronic tablets were well-received by patients and easy to use. We conclude that non-targeted HIV screening using electronic tablets would increase the HIV testing rate in our ED.

Trial Registration: ClinicalTrials.gov NCT03038724.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190767PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841645PMC
June 2018

Patient and doctor perspectives on HIV screening in the emergency department: A prospective cross-sectional study.

PLoS One 2017 21;12(7):e0180389. Epub 2017 Jul 21.

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

Background: The emergency department (ED) is mentioned specifically in the Swiss HIV testing recommendations as a site at which patients can benefit from expanded HIV testing to optimise early HIV diagnosis. At our centre, where local HIV seroprevalence is 0.2-0.4%, 1% of all patients presenting to the ED are tested for HIV. Barriers to HIV testing, from the patient and doctor perspective, and patient acceptability of rapid HIV testing were examined in this study.

Methods: Between October 2014 and May 2015, 100 discrete patient-doctor encounter pairs undertook a survey in the ED of Lausanne University Hospital, Switzerland. Patients completed a questionnaire on HIV risk factors and were offered free rapid HIV testing (INSTI™). For every patient included, the treating doctor was asked if HIV testing had 1) been indicated according to the national testing recommendations, 2) mentioned, and 3) offered during the consultation.

Results: Of 100 patients, 30 had indications for HIV testing through risk factors or a suggestive presenting complaint (PC). Fifty patients accepted rapid testing; no test was reactive. Of 50 patients declining testing, 82% considered themselves not at risk or had recently tested negative and 16% wished to focus on their PC. ED doctors identified 20 patients with testing indications, mentioned testing to nine and offered testing to six. The main reason for doctors not mentioning or not offering testing was the wish to focus on the PC.

Discussion: Patients and doctors at our ED share the testing barrier of wishing to focus on the PC. Rapid HIV testing offered in parallel to the patient-doctor consultation increased the testing rate from 6% (offered by doctors) to 50%. Introducing this service would enable testing of patients not offered tests by their doctors and reduce missed opportunities for early HIV diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180389PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521743PMC
September 2017

Investigating Barriers in HIV-Testing Oncology Patients: The IBITOP Study, Phase I.

Oncologist 2016 10 20;21(10):1176-1182. Epub 2016 Jul 20.

Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland

Background: Although the prevalence of non-AIDS-defining cancers (non-ADCs) among people living with HIV is rising, we observed HIV testing rates below 5% at our oncology center, against a regional HIV prevalence of 0.2%-0.4%. We performed the Investigating Barriers in HIV-Testing Oncology Patients (IBITOP) study among oncology physicians and patients.

Methods: Between July 1 and October 31, 2013, patients of unknown HIV status newly diagnosed with solid-organ non-ADCs referred to Lausanne University Hospital Oncology Service, Switzerland, were offered free HIV testing as part of their oncology work-up. The primary endpoints were (a) physician willingness to offer and patient acceptance of HIV testing and (b) physicians' reasons for not offering testing.

Results: Of 239 patients of unknown HIV status with a new non-ADC diagnosis, 43 (18%) were offered HIV testing, of whom 4 declined (acceptance rate: 39 of 43; 91%). Except for 21 patients tested prior to oncology consultation, 175 patients (of 239; 73%) were not offered testing. Testing rate declined among patients who were >70 years old (12% versus 30%; p = .04); no non-European patients were tested. Physicians gave reasons for not testing in 16% of cases, the main reason being patient follow-up elsewhere (10 patients; 5.7%). HIV testing during the IBITOP study increased the HIV testing rate to 18%.

Conclusion: Although the IBITOP study increased HIV testing rates, most patients were not tested. Testing was low or nonexistent among individuals at risk of late HIV presentation (older patients and migrants). Barriers to testing appear to be physician-led, because patient acceptance of testing offered was very high (91%). In November 2013, the Swiss HIV testing recommendations were updated to propose testing in cancer patients. Phase II of the IBITOP study is examining the effect of these recommendations on HIV testing rates and focusing on physician-led testing barriers.

Implications For Practice: Patients of unknown HIV status newly diagnosed with solid-organ non-AIDS-defining cancers were offered free HIV testing. Physician and patient barriers to HIV testing were examined. Most patients (82%) were not offered testing, and testing of individuals at risk of late HIV presentation (older patients and migrants) was low or nonexistent. Conversely, patient acceptance of testing offered was very high (91%), suggesting that testing barriers in this setting are physician-led. Since this study, the Swiss HIV testing recommendations now advise testing cancer patients before chemotherapy. Phase II of the Investigating Barriers in HIV-Testing Oncology Patients study is examining the effect of these recommendations on testing rates and physician barriers.
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http://dx.doi.org/10.1634/theoncologist.2016-0107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061530PMC
October 2016

Patients' understanding of blood tests and attitudes to HIV screening in the emergency department of a Swiss teaching hospital: a cross-sectional observational study.

Swiss Med Wkly 2015 4;145:w14206. Epub 2015 Dec 4.

Emergency Department, Lausanne University Hospital, Switzerland.

Background: In Switzerland, patients may undergo "blood tests" without being informed what these are screening for. Inadequate doctor-patient communication may result in patient misunderstanding. We examined what patients in the emergency department (ED) believed they had been screened for and explored their attitudes to routine (non-targeted) human immunodeficiency virus (HIV) screening.

Methods: Between 1st October 2012 and 28th February 2013, a questionnaire-based survey was conducted among patients aged 16-70 years old presenting to the ED of Lausanne University Hospital. Patients were asked: (1) if they believed they had been screened for HIV; (2) if they agreed in principle to routine HIV screening and (3) if they agreed to be HIV tested during their current ED visit.

Results: Of 466 eligible patients, 411 (88%) agreed to participate. Mean age was 46 ± 16 years; 192 patients (47%) were women; 366 (89%) were Swiss or European; 113 (27%) believed they had been screened for HIV, the proportion increasing with age (p ≤ 0.01), 297 (72%) agreed in principle with routine HIV testing in the ED, and 138 patients (34%) agreed to be HIV tested during their current ED visit.

Conclusion: In this ED population, 27% believed incorrectly they had been screened for HIV. Over 70% agreed in principle with routine HIV testing and 34% agreed to be tested during their current visit. These results demonstrate willingness among patients concerning routine HIV testing in the ED and highlight a need for improved doctor-patient communication about what a blood test specifically screens for.
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http://dx.doi.org/10.4414/smw.2015.14206DOI Listing
September 2016

Virological outcome and management of persistent low-level viraemia in HIV-1-infected patients: 11 years of the Swiss HIV Cohort Study.

Antivir Ther 2015 25;20(2):165-75. Epub 2014 Jun 25.

Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS).

Methods: In this retrospective study (2000-2011), pLLV was defined as a VL of 21-400 copies/ml on ≥ three consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥ three consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/ml.

Results: Among 9,972 patients, 179 had pLLV and 5,389 were controls. Compared to controls, pLLV patients were more often on unboosted protease inhibitor (PI)-based (adjusted odds ratio [aOR; 95% CI] 3.2 [1.8, 5.9]) and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-only combinations (aOR 2.1 [1.1, 4.2]) than on non-nucleoside reverse transcriptase inhibitor and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 [3.8, 315]), unboosted PI-based (aOR 12.8 [1.7, 96]) or NRTI-only combinations (aOR 115 [6.8, 1,952]), and VLs>200 during pLLV (aOR 3.7 [1.1, 12]). No VF occurred in patients with persistent very LLV (21-49 copies/ml; n=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared with 19/74 (26%) without change (P<0.001).

Conclusions: Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV>200 copies/ml.
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http://dx.doi.org/10.3851/IMP2815DOI Listing
January 2016

Awareness of HIV testing guidelines is low among Swiss emergency doctors: a survey of five teaching hospitals in French-speaking Switzerland.

PLoS One 2013 6;8(9):e72812. Epub 2013 Sep 6.

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

Background: In Switzerland, 30% of HIV-infected individuals are diagnosed late. To optimize HIV testing, the Swiss Federal Office of Public Health (FOPH) updated 'Provider Induced Counseling and Testing' (PICT) recommendations in 2010. These permit doctors to test patients if HIV infection is suspected, without explicit consent or pre-test counseling; patients should nonetheless be informed that testing will be performed. We examined awareness of these updated recommendations among emergency department (ED) doctors.

Methods: We conducted a questionnaire-based survey among 167 ED doctors at five teaching hospitals in French-Speaking Switzerland between 1(st) May and 31(st) July 2011. For 25 clinical scenarios, participants had to state whether HIV testing was indicated or whether patient consent or pre-test counseling was required. We asked how many HIV tests participants had requested in the previous month, and whether they were aware of the FOPH testing recommendations.

Results: 144/167 doctors (88%) returned the questionnaire. Median postgraduate experience was 6.5 years (interquartile range [IQR] 3; 12). Mean percentage of correct answers was 59 ± 11%, senior doctors scoring higher (P=0.001). Lowest-scoring questions pertained to acute HIV infection and scenarios where patient consent was not required. Median number of test requests was 1 (IQR 0-2, range 0-10). Only 26/144 (18%) of participants were aware of the updated FOPH recommendations. Those aware had higher scores (P=0.001) but did not perform more HIV tests.

Conclusions: Swiss ED doctors are not aware of the national HIV testing recommendations and rarely perform HIV tests. Improved recommendation dissemination and adherence is required if ED doctors are to contribute to earlier HIV diagnoses.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072812PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765151PMC
June 2014

An analysis of the benefit of using HEV genotype 3 antigens in detecting anti-HEV IgG in a European population.

PLoS One 2013 7;8(5):e62980. Epub 2013 May 7.

Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

Background: The benefit of using serological assays based on HEV genotype 3 in industrialised settings is unclear. We compared the performance of serological kits based on antigens from different HEV genotypes.

Methods: Taking 20 serum samples from patients in southwest France with acute HEV infection (positive PCR for HEV genotype 3) and 550 anonymised samples from blood donors in southwest Switzerland, we tested for anti-HEV IgG using three enzyme immunoassays (EIAs) (MP Diagnostics, Dia.Pro and Fortress) based on genotype 1 and 2 antigens, and one immunodot assay (Mikrogen Diagnostik recomLine HEV IgG/IgM) based on genotype 1 and 3 antigens.

Results: All acute HEV samples and 124/550 blood donor samples were positive with ≥1 assay. Of PCR-confirmed patient samples, 45%, 65%, 95% and 55% were positive with MP Diagnostics, Dia.Pro, Fortress and recomLine, respectively. Of blood donor samples positive with ≥1 assay, 120/124 (97%), were positive with Fortress, 19/124 (15%) were positive with all EIAs and 51/124 (41%) were positive with recomLine. Of 11/20 patient samples positive with recomLine, stronger reactivity for HEV genotype 3 was observed in 1/11(9%), and equal reactivity for both genotypes in 5/11 (45.5%).

Conclusions: Although recomLine contains HEV genotype 3, it has lower sensitivity than Fortress in acute HEV infection and fails to identify infection as being due to this genotype in approximately 45% of patients. In our single blood donor population, we observe wide variations in measured seroprevalence, from 4.2% to 21.8%, depending on the assay used.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062980PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646942PMC
December 2013

Impact of recommendation updates in well-controlled patients on nonrecommended antiretroviral therapies: the Swiss HIV cohort study.

J Acquir Immune Defic Syndr 2013 Feb;62(2):180-9

Department of Medicine, Infectious Diseases Service, University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored.

Methods: We selected patients with undetectable viral loads (VLs) on nonrecommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs), or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics with those of control patients with undetectable VL not on these regimens and examined clinical outcome and reasons for treatment modification.

Results: At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%), and 1 (5%) patient were still on DBPIs, triple-NRTIs, and ddI plus d4T, respectively. 'Physician decision,' excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation nonobservance included female sex [adjusted odds ratio (aOR) 2.69, 95% confidence interval (CI) 1 to 7.26; P = 0.01] for DPBIs, and undetectable VL (aOR 3.53, 95% CI 1.6 to 7.8; P = 0.002) and lack of cardiovascular events (aOR 2.93, 95% CI 1.23 to 6.97; P = 0.02) for triple-NRTIs. All patients on DBPIs with documented diabetes or a cardiovascular event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P = 0.06), and more patients having undetectable VL (P = 0.02) in the triple-NRTI group.

Conclusion: The physician's decision is the main factor driving change from nonrecommended to recommended regimens, whereas virological suppression is associated with not switching. Positive clinical outcomes observed postswitch underline the importance of observing recommendations, even in well-controlled patients.
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http://dx.doi.org/10.1097/QAI.0b013e31827b626aDOI Listing
February 2013

Cerebral vasculitis complicating postoperative meningitis: the role of steroids revisited.

Swiss Med Wkly 2012 29;142:w13697. Epub 2012 Oct 29.

Service of Infectious Diseases, Clinique Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Meningitis due to Streptococcus pneumoniae is a rare complication of trans-sphenoidal surgery. We present the case of a patient who developed pneumococcal meningitis with associated bacteraemia after elective endoscopic trans-sphenoidal resection of a pituitary macro-adenoma. After initial treatment with ceftriaxone and dexamethasone, the patient made a good recovery and dexamethasone was discontinued. Two days later the patient's condition deteriorated rapidly, presenting focal and diffuse neurological deficits. Cerebral MRI revealed widespread punctate ischaemic-type lesions affecting both anterior and posterior vascular territories bilaterally and involving features consistent with cerebral vasculitis. Antibiotic treatment was broadened to include meropenem and dexamethasone was restarted, but the patient remained in a comatose state and died 14 days later. Steroid treatment may play a dual role in this poorly characterised infectious complication of trans-sphenoidal pituitary surgery. This possibility is discussed and the options for prophylaxis are reviewed.
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http://dx.doi.org/10.4414/smw.2012.13697DOI Listing
May 2013

Increased macrophage migration inhibitory factor (MIF) plasma levels in acute HIV-1 infection.

Cytokine 2012 Nov 13;60(2):338-40. Epub 2012 Aug 13.

Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Considering macrophage migratory inhibitory factor (MIF) as a critical pro-inflammatory cytokine of the immune system, we evaluated plasma MIF levels in 89 HIV-infected adults. Plasma MIF levels were higher in HIV-infected than in HIV-negative individuals. Highest MIF levels were observed during acute HIV infection (AHI) whilst patients on antiretroviral therapy (ART) had lower MIF levels, regardless of ART efficacy. Our results suggest that MIF is an integral component of the cytokine storm characteristic of AHI.
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http://dx.doi.org/10.1016/j.cyto.2012.07.027DOI Listing
November 2012

HIV testing practices by clinical service before and after revised testing guidelines in a Swiss University Hospital.

PLoS One 2012 28;7(6):e39299. Epub 2012 Jun 28.

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

Objectives: To determine 1) HIV testing practices in a 1400-bed university hospital where local HIV prevalence is 0.4% and 2) the effect on testing practices of national HIV testing guidelines, revised in March 2010, recommending Physician-Initiated Counselling and Testing (PICT).

Methods: Using 2 hospital databases, we determined the number of HIV tests performed by selected clinical services, and the number of patients tested as a percentage of the number seen per service ('testing rate'). To explore the effect of the revised national guidelines, we examined testing rates for two years pre- and two years post-PICT guideline publication.

Results: Combining the clinical services, 253,178 patients were seen and 9,183 tests were performed (of which 80 tested positive, 0.9%) in the four-year study period. The emergency department (ED) performed the second highest number of tests, but had the lowest testing rates (0.9-1.1%). Of inpatient services, neurology and psychiatry had higher testing rates than internal medicine (19.7% and 9.6% versus 8%, respectively). There was no significant increase in testing rates, either globally or in the majority of the clinical services examined, and no increase in new HIV diagnoses post-PICT recommendations.

Conclusions: Using a simple two-database tool, we observe no global improvement in HIV testing rates in our hospital following new national guidelines but do identify services where testing practices merit improvement. This study may show the limit of PICT strategies based on physician risk assessment, compared to the opt-out approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039299PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386253PMC
March 2013

A cross-sectional survey of attitudes to HIV risk and rapid HIV testing among clients of sex workers in Switzerland.

Sex Transm Infect 2012 Oct 24;88(6):462-4. Epub 2012 May 24.

Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

Objectives: To assess attitudes to HIV risk and acceptability of rapid HIV testing among clients of street-based female sex workers (FSW) in Lausanne, Switzerland, where HIV prevalence in the general population is 0.4%.

Methods: The authors conducted a cross-sectional study in the red light district of Lausanne for five nights in September of 2008, 2009 and 2010. Clients of FSW were invited to complete a questionnaire in the street assessing demographic characteristics, attitudes to HIV risk and HIV testing history. All clients interviewed were then offered anonymous finger stick rapid HIV testing in a van parked on-site.

Results: The authors interviewed 112, 127 and 79 clients in 2008, 2009 and 2010, respectively. All were men, average age 32-37 years old; 40-60% were in a stable relationship. History of unprotected sex was higher with non-commercial partners (33-50%) than with FSW (6-11%); 29-46% of clients had never undergone an HIV test. Anonymous rapid HIV testing was accepted by 45-50% of clients. Out of 109 HIV tests conducted during the three study periods, none was reactive.

Conclusions: On-site HIV counselling and testing is acceptable among clients of FSW in this urban setting. These individuals represent an unquantified population, a proportion of which has an incomplete understanding of HIV risk in the face of high-risk behaviour, with implications for potential onward transmission to non-commercial sexual partners.
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http://dx.doi.org/10.1136/sextrans-2012-050489DOI Listing
October 2012

Immune response to hepatitis B vaccination in HIV-positive adults with isolated antibodies to HBV core antigen.

J Infect 2012 Aug 9;65(2):157-64. Epub 2012 Mar 9.

Infectious Diseases Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, 1011 Lausanne, Switzerland.

Objective: To investigate the merits of vaccination against hepatitis B virus (HBV) in HIV-positive individuals with isolated antibodies to hepatitis B core antigen (anti-HBc).

Methods: HIV-positive patients with isolated anti-HBc and CD4 counts >200 cells/mm(3) received HBV vaccination. An antibody titre to hepatitis B surface antigen (anti-HBs titres) ≥10 IU/L one month post-vaccination was termed an anamnestic response; a titre <10 IU/L was termed a primary response. Patients with primary responses received a 3-dose vaccine course. Anti-HBs titres in all responders were measured 12 and 24 months post-vaccination.

Results: 37 patients were studied: 19 (51%) were co-infected with hepatitis C; median CD4 count was 443 cells/mm(3). 8/37 patients (22%) elicited an anamnestic response. 29/37 patients (78%) elicited a primary response. After a 3-dose vaccine course, 15/25 primary responders (60%) achieved anti-HBs titres ≥10 IU/L. HIV acquisition through injecting drug use was the only independent predictor of an anamnestic response (OR 22.9, CI 1.71-306.74, P=0.018). Median anti-HBs titres for anamnestic and primary responders were 51 IU/L (13-127) and 157 IU/L (25-650) respectively. Of all responders, 12/23 (52%) retained anti-HBs titres ≥10 IU/L at 24 months. Anti-HBs duration was not significantly different between anamnestic and primary responders.

Conclusions: 23/37 HIV-positive patients (62%) with isolated anti-HBc achieved anti-HBs titres ≥10 IU/L after 1-3 vaccine doses. However, duration of this immune response was short-lived (
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http://dx.doi.org/10.1016/j.jinf.2012.03.009DOI Listing
August 2012

Hepatitis E Virus seroprevalence and chronic infections in patients with HIV, Switzerland.

Emerg Infect Dis 2011 Jun;17(6):1074-8

Centre Hospitalier Universitaire Vaudois and Lausanne University, Lausanne, Switzerland.

We screened 735 HIV-infected patients in Switzerland with unexplained alanine aminotransferase elevation for hepatitis E virus (HEV) immunoglobulin G. Although HEV seroprevalence in this population is low (2.6%), HEV RNA can persist in patients with low CD4 cell counts. Findings suggest chronic HEV infection should be considered as a cause of persistent alanine aminotransferase elevation.
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http://dx.doi.org/10.3201/eid/1706.101067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3358194PMC
June 2011

Hepatitis E virus seroprevalence among blood donors in southwest Switzerland.

PLoS One 2011 20;6(6):e21150. Epub 2011 Jun 20.

Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

Aim: The aim of this study was to determine the seroprevalence of Hepatitis E virus (HEV) among blood donors in southwest Switzerland.

Background: HEV is recognized as a food-borne disease in industrialized countries, transmitted mainly through pork meat. Cases of transmission through blood transfusion have also been reported. Recent studies have revealed seroprevalence rates of 13.5%, 16.6% and 20.6% among blood donors in England, France and Denmark, respectively.

Methods: We analyzed 550 consecutive blood donor samples collected in the region of Lausanne, canton of Vaud, Switzerland, for the presence of anti-HEV IgG, using the MP Diagnostics HEV ELISA kit. For each donor, we documented age, sex and alanine aminotransferase (ALT) value.

Results: The study panel was composed of 332 men (60.4%) and 218 women (39.6%). Overall, anti-HEV IgG was found in 27 of 550 samples (4.9%). The seroprevalence was 5.4% (18/332) in men and 4.1% (9/218) in women. The presence of anti-HEV IgG was not correlated with age, gender or ALT values. However, we observed a peak in seroprevalence of 5.3% in individuals aged 51 to 70 years old.

Conclusions: Compared with other European countries, HEV seroprevalence among blood donors in southwest Switzerland is low. The low seroprevalence may be explained by the sensitivity of commercial tests used and/or the strict regulation of animal and meat imports. Data regarding HEV prevalence in Swiss livestock are lacking and merit exploration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0021150PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3118806PMC
October 2011

Role of the cystic fibrosis transmembrane conductance regulator in internalization of Pseudomonas aeruginosa by polarized respiratory epithelial cells.

Cell Microbiol 2004 Jun;6(6):521-33

Department of Infectious Diseases, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

Pseudomonas aeruginosa is an important human pathogen, producing lung infection in individuals with cystic fibrosis (CF), patients who are ventilated and those who are neutropenic. The respiratory epithelium provides the initial barrier to infection. Pseudomonas aeruginosa can enter epithelial cells, although the mechanism of entry and the role of intracellular organisms in its life cycle are unclear. We devised a model of infection of polarized human respiratory epithelial cells with P. aeruginosa and investigated the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in adherence, uptake and IL-8 production by human respiratory epithelial cells. We found that a number of P. aeruginosa strains could invade and replicate within cells derived from a patient with CF. Intracellular bacteria did not produce host cell cytotoxicity over a period of 24 h. When these cells were transfected with wild-type CFTR, uptake of bacteria was significantly reduced and release of IL-8 following infection enhanced. We propose that internalized P. aeruginosa may play an important role in the pathogenesis of infection and that, by allowing greater internalization into epithelial cells, mutant CFTR results in an increased susceptibility of bronchial infection with this microbe.
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http://dx.doi.org/10.1111/j.1462-5822.2004.00380.xDOI Listing
June 2004

Effects of nitric oxide on Pseudomonas aeruginosa infection of epithelial cells from a human respiratory cell line derived from a patient with cystic fibrosis.

Infect Immun 2003 May;71(5):2341-9

Department of Infectious Diseases, Faculty of Medicine, Imperial College, Hammersmith Hospital, London W12 0NN, United Kingdom.

Cystic fibrosis (CF) is characterized by airway inflammation and chronic bacterial lung infection, most commonly with Pseudomonas aeruginosa, an opportunistic human pathogen. Despite the persistent airway inflammation observed in patients with CF, although phagocyte inducible nitric oxide synthase (iNOS) production is upregulated, expression of iNOS in the respiratory epithelium is markedly reduced. Given the antimicrobial action of NO, this may contribute to the chronic airway infection of this disease. To define the role of epithelium-derived NO in airway defense against P. aeruginosa, we infected differentiated human bronchial epithelial cells derived from a patient with CF (CFBE41o- cells) with different strains of this pathogen at low multiplicities of infection. Using cells transfected with human iNOS cDNA, we studied the effect of NO on P. aeruginosa replication, adherence, and internalization. P. aeruginosa adherence to iNOS-expressing cells was reduced by 44 to 72% (P = 0.02) compared with control values. Absolute P. aeruginosa uptake into these cells was reduced by 44%, but uptake expressed as a percentage of adherent bacteria did not differ from the control uptake. Survival of P. aeruginosa within iNOS-expressing cells was reduced at late times postinfection (P = 0.034). NO production did not alter host cell viability. NO production reduced P. aeruginosa adherence to human bronchial epithelial cells and enhanced killing of internalized bacteria, suggesting that a lack of epithelial iNOS in patients with CF may contribute to P. aeruginosa infection and colonization.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC153226PMC
http://dx.doi.org/10.1128/iai.71.5.2341-2349.2003DOI Listing
May 2003

Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output.

J Biol Chem 2002 Sep 21;277(36):33132-8. Epub 2002 Jun 21.

Department of Infectious Diseases, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom.

Nitric oxide (NO), produced via inducible NO synthase (iNOS), can modulate polarized epithelial processes such as solute transport. Given the high reactivity of NO, we hypothesized that optimal NO regulation of polarized epithelial functions is achieved through compartmentalization of iNOS, allowing local NO delivery to its molecular targets. Here, we show that iNOS localizes to the apical domain of epithelial cells within a submembranous protein complex tightly bound to cortical actin. We further show that iNOS can bind to the apical PDZ protein, EBP50 (ezrin-radixin-moesin-binding phosphoprotein 50), an interaction that is dependent on the last three COOH-terminal amino acids of iNOS, SAL, but requires the presence of additional unknown cellular proteins. Mutation of these three COOH-terminal residues abolishes the iNOS-EBP50 interaction and disrupts the apical association of iNOS in transfected cells, showing that this COOH-terminal motif is essential for the correct localization of iNOS in epithelial cells. Apically localized iNOS directs vectorial NO production at the apical proximal tubule epithelial cell surface. These studies define human epithelial iNOS as an apical EBP50-binding protein and suggest that the physical association of iNOS with EBP50 might allow precise NO modulation of EBP50-associated protein functions.
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http://dx.doi.org/10.1074/jbc.M205764200DOI Listing
September 2002