Publications by authors named "Philip E Tarr"

79 Publications

Neurocognitive course at two-year follow-up in the neurocognitive assessment in the metabolic and aging cohort (NAMACO) study.

AIDS 2021 Aug 19. Epub 2021 Aug 19.

Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland Department of Infectious Diseases and Hospital Epidemiology, Universitätsspital Zurich, University of Zurich, Zurich, Switzerland Laboratory of Neuroimmunology, Research Centre of clinical neurosciences, Department of clinical neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland University Department of Medicine, Kantonsspital Bruderholz, University of Basel, Bruderholz, Switzerland Department of Infectious Diseases and Hospital Epidemiology, Universitätsspital Basel, University of Basel, Basel, Switzerland Memory Clinic, Felix Platter Hospital, University Center for Medicine of Aging, Basel, Switzerland Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurology, Bern University Hospital, University of Bern, Bern, Switzerland HIV unit, Infectious Diseases Division, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland Department of Neurology, University Hospital of Geneva and Faculty of Medicine, Geneva, Switzerland Division of Infectious Diseases and Hospital Epidemiology Division, Kantonsspital St. Gallen, St. Gallen, Switzerland Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland Infectious Diseases Division, Ospedale Regionale di Lugano, Lugano, Switzerland Department of Neurology, Neurocentre of Southern Switzerland, Ospedale Civico, Lugano, Switzerland Neuropsychology Unit, Department of Neurology, Universitätsspital Zurich, University of Zurich, Zurich, Switzerland Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Objective: To examine neurocognitive course over time among people with well-treated HIV.

Design: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up.

Setting: Seven SHCS centers.

Subjects: Patients aged ≥45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at two-year follow-up of whom 644 had complete data sets.

Intervention: Standardized neuropsychological assessment at baseline and two-year follow-up.

Main Outcome Measure: Neurocognitive performance using Frascati criteria and mean z-scores.

Results: Four participants (of 644, 0.6%) had plasma HIV-1 RNA > 50 copies/mL; median CD4 count was 660 cells/μL. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over two years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age ≥65 years (p = 0.02) and cognitive complaints (p = 0.004) were associated with neurocognitive decline, while black race (p = 0.01) and dolutegravir treatment (p = 0.002) were associated with improvement.

Conclusion: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well-treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.
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http://dx.doi.org/10.1097/QAD.0000000000003057DOI Listing
August 2021

Coronary Artery Disease-associated and Longevity-associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living with HIV: The Swiss HIV Cohort Study.

Clin Infect Dis 2021 Jun 6. Epub 2021 Jun 6.

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

Background: Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with HIV (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRS) and by considering genetic variants associated with successful aging and longevity.

Methods: In Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (OR) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRS. PRS were built from CAD-associated single nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.

Results: We included 269 cases with CAD events between 2000-2017 (Median age 54 years, 87% male, 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (i.e. traditional and HIV-related) risk factors, and PRS built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (p<0.001). Participants with the most unfavorable clinical risk factor profile (top quintile) had adjusted CAD-OR=17.82 (8.19-38.76), compared to participants in the bottom quintile. Participants with the most unfavorable CAD-PRS (top quintile) had adjusted CAD-OR=3.17 (1.74-5.79), compared to the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had adjusted CAD-OR=3.67 (2.00-6.73), compared to the bottom quintile.

Conclusions: In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related and genetic risk factors provided the most powerful CAD prediction.
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http://dx.doi.org/10.1093/cid/ciab521DOI Listing
June 2021

Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length.

J Infect Dis 2021 Apr 5. Epub 2021 Apr 5.

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

Background: Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI).

Methods: We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for >6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL.

Results: In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p<0.001), not if ART was interrupted >12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p<0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables.

Discussion: In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.
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http://dx.doi.org/10.1093/infdis/jiab186DOI Listing
April 2021

Application of the Parent Attitudes about Childhood Vaccines (PACV) survey in three national languages in Switzerland: Exploratory factor analysis and Mokken scale analysis.

Hum Vaccin Immunother 2021 08 24;17(8):2652-2660. Epub 2021 Mar 24.

University of Basel, Basel, Switzerland.

Vaccine hesitancy (VH) is a complex and context-specific phenomenon that is linked to under-immunization and poses challenges to immunization programs. The Parent Attitudes about Childhood Vaccines (PACV) is an instrument developed to measure VH. We translated the PACV into three languages (German, French and Italian) and administered it to 1388 Swiss parents. We used exploratory factor analysis (EFA) to confirm the scale sub-domains, Cronbach's alpha to assess internal consistency reliability, and Mokken scale analysis (MSA), to explore unidimensionality of each language version. We determined to construct validity by linking parental PACV score to children's immunization status for the first dose of measles vaccine. For the 15-item PACV, EFA extracted three sub-domains in German and French and four sub-domains in Italian. Cronbach's alpha was >0.8 across the three languages, and MSA produced a 13-item German, 14-item French, and 11-item Italian PACV. EFA and MSA of the short version PACV extracted a single factor and scale with Cronbach's alpha >0.7 in all three language versions. VH was significantly associated with non-timely receipt of the first dose of measles in all languages (odds ratio of 20.7, 21.3, and 8.3 for German, French, and Italian languages, respectively). The translated and revised PACV-15 versions are valid and reliable instruments for VH measurement. The structure and reliability of the short version of the PACV was as good as the long version. Our results suggest that the PACV can be used to measure parental VH outside the US in the validated languages.
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http://dx.doi.org/10.1080/21645515.2021.1894894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475569PMC
August 2021

Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV : A Cohort Study.

Ann Intern Med 2021 06 16;174(6):758-767. Epub 2021 Mar 16.

Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (B.S., C.M., H.F., G.W., A.R.).

Background: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain.

Objective: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF.

Design: Cohort study.

Setting: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland.

Participants: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer.

Measurements: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions tests.

Results: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months.

Limitation: Short follow-up, small subgroup analyses, and potential residual confounding.

Conclusion: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels.

Primary Funding Source: Swiss National Science Foundation.
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http://dx.doi.org/10.7326/M20-4853DOI Listing
June 2021

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
August 2021

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

J Antimicrob Chemother 2021 02;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

Rapid Progression of Kidney Dysfunction in People Living With HIV: Use of Polygenic and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Risk Scores.

J Infect Dis 2021 Jun;223(12):2145-2153

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

Background: In people with human immunodeficiency virus (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction (ie, estimated glomerular filtration rate [eGFR] decrease of >5mL/min/1.73m2 per year for ≥3 consecutive years).

Methods: We obtained univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D chronic kidney disease (CKD) risk score, antiretroviral exposures, and a polygenic risk score based on 14 769 genome-wide single nucleotide polymorphisms in white Swiss HIV Cohort Study participants.

Results: We included 225 participants with rapid progression and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with low D:A:D risk, participants with high risk had rapid progression (HR =  1.82 [95% CI, 1.28-2.60]). Compared to the first (favorable) polygenic risk score quartile, participants in the second, third, and fourth (unfavorable) quartiles had rapid progression (HR = 1.39 [95% CI, 0.94-2.06], 1.52 [95% CI, 1.04-2.24], and 2.04 [95% CI, 1.41-2.94], respectively). Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR = 1.36 [95% CI, 1.06-1.76]).

Discussion: An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors.
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http://dx.doi.org/10.1093/infdis/jiaa695DOI Listing
June 2021

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

Telomere Length, Traditional Risk Factors, Factors Related to Human Immunodeficiency Virus (HIV) and Coronary Artery Disease Events in Swiss Persons Living With HIV.

Clin Infect Dis 2021 10;73(7):e2070-e2076

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 human immunodeficiency virus (HIV; PLWH) may have accelerated atherosclerosis and shorter TL than the general population. It is unknown whether TL is associated with CAD in PLWH.

Methods: We measured TL by quantitative polymerase chain reaction (PCR) in white Swiss HIV Cohort Study participants. Cases had a first CAD event during 1 January 2000 to 31 December 2017. We matched 1-3 PLWH controls without CAD events on sex, age, and observation time. We obtained univariable and multivariable odds ratios (OR) for CAD from conditional logistic regression analyses.

Results: We included 333 cases (median age 54 years; 14% women; 83% with suppressed HIV RNA) and 745 controls. Median time (interquartile range) of TL measurement was 9.4 (5.9-13.8) years prior to CAD event. Compared to the 1st (shortest) TL quintile, participants in the 5th (longest) TL quintile had univariable and multivariable CAD event OR = 0.56 (95% confidence interval [CI], .35-.91) and OR = 0.54 (95% CI, .31-.96). Multivariable OR for current smoking was 1.93 (95% CI, 1.27-2.92), dyslipidemia OR = 1.92 (95% CI, 1.41-2.63), and for recent abacavir, cumulative lopinavir, indinavir, and darunavir exposure was OR = 1.82 (95% CI, 1.27-2.59), OR = 2.02 (95% CI, 1.34-3.04), OR = 3.42 (95% CI, 2.14-5.45), and OR = 1.66 (95% CI, 1.00-2.74), respectively. The TL-CAD association remained significant when adjusting only for Framingham risk score, when excluding TL outliers, and when adjusting for CMV-seropositivity, HCV-seropositivity, time spent with detectable HIV viremia, and injection drug use.

Conclusions: In PLWH, TL measured >9 years before, is independently associated with CAD events after adjusting for multiple traditional and HIV-related factors.
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http://dx.doi.org/10.1093/cid/ciaa1034DOI Listing
October 2021

Intra-Abdominal Nocardiosis-Case Report and Review of the Literature.

J Clin Med 2020 Jul 7;9(7). Epub 2020 Jul 7.

University Department of Medicine, Kantonsspital Baselland, University of Basel, 4101 Bruderholz, Switzerland.

Nocardiosis is primarily an opportunistic infection affecting immunosuppressed individuals, in whom it most commonly presents as pulmonary infection and sometimes cerebral abscesses. Isolated abdominal or retroperitoneal nocardiosis is rare. Here, we report the second case, to our knowledge, of isolated abdominal nocardiosis due to and provide a comprehensive review of intra-abdominal nocardiosis. The acquisition of abdominal nocardiosis is believed to occur via hematogenous spreading after pulmonary or percutaneous inoculation or possibly via direct abdominal inoculation. Cases of peritonitis have been reported in patients on peritoneal dialysis. Accurate diagnosis of abdominal nocardiosis requires histological and/or microbiological examination of appropriate, radiologically or surgically obtained biopsy specimens. Malignancy may initially be suspected when the patient presents with an abdominal mass. Successful therapy usually includes either percutaneous or surgical abscess drainage plus prolonged combination antimicrobial therapy.
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http://dx.doi.org/10.3390/jcm9072141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408857PMC
July 2020

'Problem patients and physicians' failures': What it means for doctors to counsel vaccine hesitant patients in Switzerland.

Soc Sci Med 2020 06 3;255:112946. Epub 2020 Apr 3.

University of Basel, Petersplatz 1, 4001, Basel, Switzerland; University Department of Medicine, Kantonsspital Baselland, University of Basel, 4101, Bruderholz, Switzerland. Electronic address:

This article reports on our qualitative inquiry into the meanings biomedically trained doctors in Switzerland attach to treating vaccine hesitant (VH) and underimmunized patients. With support from social science literature on 'good' and 'bad' patients and doctors, we explore how both doctors and patients cross the boundaries of these conceptual categories in situations involving vaccine hesitancy and underimmunization. The doctors we interviewed (N = 20) and observed (N = 16 observations, subsample of 6 doctors from the interview sample) described how they screened, measured, and diagnosed patients' levels of vaccine hesitancy. Our results emphasize the meanings doctors associated with counseling hesitant patients, especially while managing their own professional responsibilities, legitimacy, and reputations among colleagues and patients. Doctors' discourses constructed the figure of 'problem patients,' characterized through their (potential) non-adherence to vaccination recommendations, desire for lengthy consultations and individualized counseling, and dogmatic ideologies running contra to biomedicine. Discussions around the dilemmas faced by doctors in vaccination consultations brings to the fore several key, yet underdiscussed, paradoxes concerning VH, patient-doctor relationships, and the constructs of 'good'/'bad' doctors and patients. These paradoxes revolve around expectations in Western societies for 'good' patients to be autonomous health-information seekers and active participants in clinical encounters, which research shows to be the case for many VH and underimmunizing individuals. However, in the eyes of many vaccination advocates and proponents of biomedical approaches, VH patients become 'bad' patients thru their risk of non-adherence, which has implications for the population at large. In these consultations, doctors find themselves conflicted around the expectations to promote vaccination while, at the same time, being active listeners and good communicators with those who question their biomedical training and legitimacy. Understanding these paradoxes highlights the need to better support HCPs in addressing VH in clinical practice.
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http://dx.doi.org/10.1016/j.socscimed.2020.112946DOI Listing
June 2020

Collaborating with Complementary and Alternative Medicine (CAM) Providers When Writing HPV Vaccine Review Articles.

J Clin Med 2020 Feb 21;9(2). Epub 2020 Feb 21.

University of Basel, 4051 Basel, Switzerland.

Novel strategies are needed to address vaccine hesitancy (VH), which correlates with complementary and alternative medicine (CAM). In Switzerland, CAM providers play important roles in vaccine counseling of vaccine hesitant (VH) parents, and traditional vaccination messaging tends to overlook CAM provider perspectives. In the setting of a Swiss national research program on VH, our key strategy has been to work together closely with CAM providers. To assess the feasibility of generating educational human papillomavirus (HPV) vaccine materials that would interest VH healthcare providers (HCPs), we invited four CAM providers to co-author two HPV vaccine review articles for general practitioners. We conducted thematic analysis of CAM provider comments to identify patterns that could complement and improve vaccination messaging from CAM perspectives. We identified several themes and generated an inventory of CAM provider messaging recommendations related to language use, presentation of background information, nuanced statements regarding HPV vaccine efficacy and safety, and communication tools that would be important to VH HCPs. Contrary to our initial expectations, and in an inclusive, respectful atmosphere of open dialogue, we were able to productively finalize our manuscripts. In the opinion of the CAM co-authors, the manuscripts effectively considered the communication needs and perspectives of VH HCPs. Engaging with CAM providers appears to be a feasible and innovative avenue for providing vaccine information and designing communication tools aimed at VH healthcare providers.
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http://dx.doi.org/10.3390/jcm9020592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074104PMC
February 2020

Recurrent Campylobacter Enteritis in Patients with Hypogammaglobulinemia: Review of the Literature.

J Clin Med 2020 Feb 18;9(2). Epub 2020 Feb 18.

University Department of Medicine, Kantonsspital Baselland, Bruderholz, University of Basel, 4101 Bruderholz, Switzerland.

Recurrent enteritis is a well-recorded complication of primary hypogammaglobulinemia but has only rarely been reported with other types of immunodeficiency, and no cases have been reported after rituximab-associated secondary hypogammaglobulinemia. We therefore reviewed our local microbiology laboratory databases and conducted a literature search, to provide a detailed characterization of the immunodeficiency states associated with recurrent enteritis. Published cases had primary hypogammaglobulinemia, most frequently in the setting of common variable immunodeficiency, x-linked agammaglobulinemia, and Good syndrome. No cases were identified in the literature after rituximab or secondary hypogammaglobulinemia. We report a 73-year-old patient with recurrent enteritis and hypogammaglobulinemia in the setting of non-Hodgkin lymphoma, chemotherapy, and maintenance rituximab. Physicians should be aware of the association of recurrent enteritis and immunodeficiency, most commonly in primary hypogammaglobulinemia. Rituximab alone may not be sufficiently immunosuppressive for recurrent campylobacteriosis to occur; additional factors, including hematological malignancy and its treatment, appear necessary. Patients with recurrent enteritis and those starting rituximab should be investigated for hypogammaglobulinemia and B-lymphopenia.
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http://dx.doi.org/10.3390/jcm9020553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074135PMC
February 2020

Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy.

Open Forum Infect Dis 2020 Jan 22;7(1):ofz464. Epub 2020 Jan 22.

Center for Research and Innovation in Clinical Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Lausanne, Lausanne, Switzerland.

Objective: There is limited data on abdominal obesity and the influence of genetics on weight change after antiretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) change over time in the Swiss HIV Cohort study (SHCS).

Methods: Mixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background.

Results: Individuals with CD4 nadir <100 cells/µL gained 6.4 times more BMI than individuals with ≥200, and 2.8 times more WHR than individuals with ≥100 ( < .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir <100 cells/µL compared to 100-199 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.63-2.74) and ≥200 (OR, 1.69; 95% CI, 1.26-2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir <100 compared to ≥100 (OR, 1.35; 95% CI, 1.17-1.54 [in men]; OR, 1.36; 95% CI, 1.18-1.57 [in women]), persisting after 10 years of ART. No significant differences were found across antiretroviral drug classes or genetic scores.

Conclusions: The risk of general and abdominal obesity increased with CD4 nadir <100 cells/µL. Based on our results, including the genetic background would not improve obesity predictions in HIV-infected individuals.
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http://dx.doi.org/10.1093/ofid/ofz464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974740PMC
January 2020

Determinants of vaccine hesitancy in Switzerland: study protocol of a mixed-methods national research programme.

BMJ Open 2019 11 2;9(11):e032218. Epub 2019 Nov 2.

University of Basel, Basel, Switzerland

Introduction: Vaccine hesitancy is a complex public health issue referring to concerns about the safety, efficacy or need for vaccination. Relatively little is known about vaccine hesitancy in Switzerland. This ongoing study (2017-2021) focuses on biomedical and complementary and alternative medicine (CAM) providers and their patients since healthcare professionals play important roles in vaccination decision-making. This national research programme seeks to assess the sociocultural determinants of vaccine hesitancy regarding childhood and human papillomavirus vaccines in Switzerland. We aim to provide a detailed characterisation of vaccine hesitancy, including CAM and biomedical perspectives, patient-provider interactions, and sociocultural factors, to establish the mediating effects of vaccine hesitancy on underimmunisation, and to design an intervention to improve vaccination communication and counselling among physicians, parents and adolescents.

Methods And Analysis: Our transdisciplinary team employs a sequential exploratory mixed-methods study design. We have established a network of more than 150 medical providers across Switzerland, including more than 40 CAM practitioners. For the qualitative component, we conduct interviews with parents, youth, and biomedical and CAM providers and observations of vaccination consultations and school vaccination information sessions. For the quantitative component, a sample of 1350 parents of young children and 722 young adults (15-26 years) and their medical providers respond to questionnaires. We measure vaccine hesitancy with the Parent Attitudes about Childhood Vaccines 15-item survey and review vaccination certificates to assess vaccination status. We administer additional questions based on findings from qualitative research, addressing communication with medical providers, vaccine information sources and perceptions of risk control vis-à-vis vaccine-preventable diseases. The questionnaires capture sociodemographics, political views, religion and spirituality, and moral foundations.

Ethics And Dissemination: The study was approved by the local ethics committee. The results will be published in peer-reviewed journals and disseminated to healthcare professionals, researchers and the public via conferences and public presentations.
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http://dx.doi.org/10.1136/bmjopen-2019-032218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830664PMC
November 2019

"We treat humans, not herds!": A qualitative study of complementary and alternative medicine (CAM) providers' individualized approaches to vaccination in Switzerland.

Soc Sci Med 2019 11 16;240:112556. Epub 2019 Sep 16.

University of Basel, Petersplatz 1, 4001, Basel, Switzerland; University Department of Medicine, Kantonsspital Baselland, University of Basel, Kantonsspital Baselland, University of Basel, CH-4101, Bruderholz, Switzerland. Electronic address: https://www.nfp74.ch/en/projects/out-patient-care/project-tarr.

Complementary and alternative medicine (CAM) providers' roles in parents' decision-making about vaccinations for their children have only recently begun receiving research attention, despite studies showing CAM to be used by 25-50% of the population in Western countries. This article examines how CAM practitioners discuss vaccinations with parents in Switzerland, with a focus on childhood vaccinations and human papillomavirus (HPV) vaccinations. We describe how the CAM providers we interviewed (N = 17) and observed during vaccination consultations (N = 18 observations with 5 providers) employed individualized approaches to vaccination. Triangulation of qualitative evidence from interviews and observations allowed us to analyze their discourses and descriptions of experiences (i.e. what they said) and their practices in situ (i.e. what they did). Evidence gathered shows that practitioners framed vaccination decisions as choices at individual and family levels rather than focusing on public health benefits and consequences. They articulated their perspectives in terms of personal clinical experiences and parents' wishes, concerns, and contexts. Such findings challenge recurring narratives depicting CAM providers as categorically anti-vaccination and suggest that approaches to address vaccine hesitancy in clinical practice could benefit from communication and relational approaches similar to those demonstrated by participants in this study. Such approaches include taking time to understand parents' wishes, involving them in vaccination decisions, and taking their concerns seriously.
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http://dx.doi.org/10.1016/j.socscimed.2019.112556DOI Listing
November 2019

Self-reported Neurocognitive Impairment in People Living With Human Immunodeficiency Virus (HIV): Characterizing Clusters of Patients With Similar Changes in Self-reported Neurocognitive Impairment, 2013-2017, in the Swiss HIV Cohort Study.

Clin Infect Dis 2020 07;71(3):637-644

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

Background: Self-reported neurocognitive impairment (SRNI) in people living with human immunodeficiency virus type 1 (HIV-1) infection is frequent. We use longitudinal information on SRNI in the Swiss HIV Cohort Study (SHCS) to identify and characterize groups of patients with persisting SRNI over time.

Methods: We included all SHCS patients who were assessed for SRNI during at least 5 visits spanning at least 2.5 years in 2013-2017. We first compared patients with SRNI to those without SRNI over the whole study period. Second, we used a hierarchical cluster algorithm to identify groups of patients with similar changes of SRNI over time. In both analyses, we studied clinical and demographic factors potentially influencing SRNI.

Results: In total, 79 683 questionnaires of 11 029 patients contained information about SRNI, and 8545 of 11 029 (77.5%) patients had longitudinal information. The overall percentage of patients with SRNI decreased from 19.6% in 2013 to 10.7% in 2017. Compared to patients in the cluster with low-level SRNI over time, patients in the cluster with high-level persisting SRNI more often had a prior opportunistic infection of the central nervous system (CNS) (odds ratio [OR], 3.7; P < .001), imperfect adherence to antiretroviral therapy (ART) (OR, 2.8; P < .001), and depression (OR, 1.9; P < .001).

Conclusions: Although overall SRNI is decreasing in the SHCS, there is a group of patients with persisting SRNI over time. Past opportunistic infections of the CNS, imperfect adherence to ART, and depression were associated most with persisting SRNI. Patients with these characteristics should be preferentially tested for neurocognitive impairment.Although overall self-reported neurocognitive impairment (SRNI) is decreasing in the Swiss HIV Cohort Study, there is a group of patients with persisting SRNI over time, characterized by more past opportunistic infections of the central nervous system, imperfect adherence to antiretroviral therapy, and depression.
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http://dx.doi.org/10.1093/cid/ciz868DOI Listing
July 2020

Subclinical Atherosclerosis Imaging in People Living with HIV.

J Clin Med 2019 Jul 29;8(8). Epub 2019 Jul 29.

University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, 4101 Bruderholz, Switzerland.

In many, but not all studies, people living with HIV (PLWH) have an increased risk of coronary artery disease (CAD) events compared to the general population. This has generated considerable interest in the early, non-invasive detection of asymptomatic (subclinical) atherosclerosis in PLWH. Ultrasound studies assessing carotid artery intima-media thickness (CIMT) have tended to show a somewhat greater thickness in HIV+ compared to HIV-, likely due to an increased prevalence of cardiovascular (CV) risk factors in PLWH. Coronary artery calcification (CAC) determination by non-contrast computed tomography (CT) seems promising to predict CV events but is limited to the detection of calcified plaque. Coronary CT angiography (CCTA) detects calcified and non-calcified plaque and predicts CAD better than either CAC or CIMT. A normal CCTA predicts survival free of CV events over a very long time-span. Research imaging techniques, including black-blood magnetic resonance imaging of the vessel wall and 18F-fluorodeoxyglucose positron emission tomography for the assessment of arterial inflammation have provided insights into the prevalence of HIV-vasculopathy and associated risk factors, but their clinical applicability remains limited. Therefore, CCTA currently appears as the most promising cardiac imaging modality in PLWH for the evaluation of suspected CAD, particularly in patients <50 years, in whom most atherosclerotic coronary lesions are non-calcified.
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http://dx.doi.org/10.3390/jcm8081125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723163PMC
July 2019

Systematic De-escalation of Successful Triple Antiretroviral Therapy to Dual Therapy with Dolutegravir plus Emtricitabine or Lamivudine in Swiss HIV-positive Persons.

EClinicalMedicine 2018 Dec 6;6:21-25. Epub 2018 Dec 6.

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

Background: Studies increasingly suggest that the efficacy of certain dual antiretroviral therapy (ART) combinations is equal to triple ART. Increasing concerns among HIV-positive patients and physicians in Switzerland include ART cost and long-term ART safety and toxicity, i.e. taking only as many ART agents as necessary. The aims of this retrospective analysis are to report on the de-escalation of our entire clinic population of eligible patients with well-controlled HIV-infection to dolutegravir-containing dual ART.

Methods: Starting in March 2015, we systematically considered the de-escalation of eligible patients to either dolutegravir/emtricitabine or dolutegravir/lamivudine, by discontinuing tenofovir disoproxil fumarate or abacavir. We report on the virological efficacy, tolerability and patient satisfaction ≥ 48 weeks after de-escalation.

Findings: Of 106 HIV-positive patients followed in our clinic, 70 patients were de-escalated. Three returned to triple ART (insomnia after dolutegravir start, n = 2; new wish for single tablet regimen, n = 1). All de-escalated patients and all who continued triple ART had suppressed HIV viremia at last follow-up and were satisfied with their ART regimen, except for one patient who had virological failure after ART discontinuation in the setting of major depression. The most common reasons to not de-escalate included hepatitis B co-infection (n = 6), physician's concern about ART adherence (n = 6), patient reluctance to switch from a single tablet to a 2-tablet regimen (n = 7), patient satisfied with current ART (n = 5) and others (n = 12).

Interpretation: ART de-escalation to dolutegravir/FTC or dolutegravir/3TC is possible in the majority of patients virologically suppressed on triple ART, and may effectively address patient and physician concerns about long-term safety and cost of ART.
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http://dx.doi.org/10.1016/j.eclinm.2018.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537552PMC
December 2018

Measles in Switzerland - progress made, but communication challenges lie ahead.

Swiss Med Wkly 2019 06 11;149:w20105. Epub 2019 Jun 11.

Centre for Integrative Paediatrics, Department of Paediatrics, Fribourg Hospital HFR, and Faculty of Science and Medicine, University of Fribourg, Switzerland.

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http://dx.doi.org/10.4414/smw.2019.20105DOI Listing
June 2019

The comparative effectiveness of NRTI-sparing dual regimens in emulated trials using observational data from the Swiss HIV Cohort Study.

Antivir Ther 2019 ;24(5):343-353

Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, University of Basel, Basel, Switzerland.

Background: Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) cause side effects in some patients, prompting the use of either partly or fully NRTI-sparing regimens.

Methods: We used data from the Swiss HIV Cohort Study to estimate the effectiveness of two new dolutegravir dual regimens relative to the alternative NRTI-sparing dual regimens that our clinicians used previously. We emulated two trials by propensity score matching case patients on the dolutegravir regimen with control patients on an alternative regimen. We analysed the case control sets using a Bayesian Cox model and estimated effectiveness as the percentage still on their trial regimen without virological failure at 48 weeks.

Results: In a comparison of partly NRTI-sparing regimens, 58 cases treated with dolutegravir were matched to 17 controls treated with boosted darunavir (both with lamivudine or emtricitabine). The estimated difference in effectiveness was 15% (95% credible interval [CrI] 2-33) and 12% (95% CrI 0-26) in two sequential analyses 1 year apart. In a comparison of fully NRTI-sparing regimens, 54 cases treated with dolutegravir were matched to 32 controls treated with raltegravir (both with boosted darunavir). The estimated difference in effectiveness was 9% (95% CrI -1-21) and 5% (95% CrI -4-15) in the two sequential analyses.

Conclusions: Estimates of relative effectiveness suggest that both dolutegravir regimens are not inferior to these alternative regimens. All four regimens seem suitable for patients needing an NRTI-sparing regimen: there were few virological failures and few treatment changes due to toxicity.
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http://dx.doi.org/10.3851/IMP3310DOI Listing
July 2020

Antiretroviral Drugs Associated With Subclinical Coronary Artery Disease in the Swiss Human Immunodeficiency Virus Cohort Study.

Clin Infect Dis 2020 02;70(5):884-889

Department of Medicine and Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.

Background: Coronary artery disease (CAD) events have been associated with certain antiretroviral therapy (ART) agents. In contrast, the influence of ART on subclinical atherosclerosis is not clear. The study objective was to assess the association between individual ART agents and the prevalence and extent of subclinical CAD.

Methods: Coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) were performed in ≥45-year-old Swiss Human Immunodeficiency Virus Cohort Study participants. The following subclinical CAD endpoints were analyzed separately: CAC score >0, any plaque, calcified plaque, noncalcified/mixed plaque, segment involvement score (SIS), and segment severity score (SSS). Logistic regression models calculated by inverse probability of treatment weights (IPTW) were used to explore associations between subclinical CAD and cumulative exposure to the 10 most frequently used drugs.

Results: There were 403 patients who underwent CCTA. A CAC score >0 was recorded in 188 (47%), any plaque in 214 (53%), calcified plaque in 151 (38%), and noncalcified/mixed plaque in 150 (37%) participants. A CAC score >0 was negatively associated with efavirenz (IPTW adjusted odds ratio per 5 years 0.73, 95% confidence interval [CI] 0.56-0.96), tenofovir disoproxil fumarate (0.68, 95% CI 0.49-0.95), and lopinavir (0.64, 95% CI 0.43-0.96). Any plaque was negatively associated with tenofovir disoproxil fumarate (0.71, 95% CI 0.51-0.99). Calcified plaque was negatively associated with efavirenz (0.7, 95% CI 0.57-0.97). Noncalcified/mixed plaque was positively associated with abacavir (1.46, 95% CI 1.08-1.98) and negatively associated with emtricitabine (0.67, 95% CI 0.46-0.99). For SSS and SIS, we found no association with any drug.

Conclusions: An increased risk of noncalcified/mixed plaque was only found in patients exposed to abacavir. Emtricitabine was negatively associated with noncalcified/mixed plaque, while tenofovir disoproxil fumarate and efavirenz were negatively associated with any plaque and calcified plaque, respectively.
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http://dx.doi.org/10.1093/cid/ciz283DOI Listing
February 2020

Contribution of Genetic Background and Data Collection on Adverse Events of Anti-human Immunodeficiency Virus (HIV) Drugs (D:A:D) Clinical Risk Score to Chronic Kidney Disease in Swiss HIV-infected Persons With Normal Baseline Estimated Glomerular Filtration Rate.

Clin Infect Dis 2020 02;70(5):890-897

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

Background: In human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown.

Methods: We applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m2). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms.

Results: We included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m2 (n = 144) or ≥25% eGFR drop to <90 mL/minute/1.73 m2 (n = 599), and 322 controls (eGFR drop <15%). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval [CI], 1.55-2.97) in participants in the fourth (most unfavorable) vs first (most favorable) genetic score quartile; 1.94 (95% CI, 1.37-2.65) in the fourth vs first D:A:D score quartile; and 2.98 (95% CI, 2.02-4.66), 1.70 (95% CI, 1.29-2.29), and 1.83 (95% CI, 1.45-2.40), per 5 years of exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the first genetic score quartile had no increased CKD risk, even if they were in the fourth D:A:D score quartile.

Conclusions: Genetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD.
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http://dx.doi.org/10.1093/cid/ciz280DOI Listing
February 2020

Psoas Abscess Due to in A Patient with Chronic Lymphocytic Leukemia-Case Report and Review.

J Clin Med 2019 Feb 7;8(2). Epub 2019 Feb 7.

University Department of Medicine, Kantonsspital Baselland, University of Basel, 4101 Bruderholz, Switzerland.

Infections may constitute a serious complication in patients with chronic lymphocytic leukemia (CLL). New treatment agents including obinutuzumab and ibrutinib have improved the progression-free survival in CLL, and data suggest a similar overall infection risk and a limited risk of opportunistic infections when compared to standard chemo-immunotherapy. Nevertheless, cases of opportunistic infections including non-tuberculous mycobacterial (NTM) in CLL patients have recently been published. We present a case of a 74-year old man with extensive prior CLL treatment history, including most recently obinutuzumab. He developed an abscess of the psoas muscle and inguinal lymphadenopathy. An inguinal node biopsy specimen showed infection with , confirmed by broad-spectrum mycobacterial PCR, -specific PCR, and mycobacterial culture. This case and our literature review suggest that physicians should be aware of opportunistic infections in patients with CLL. Diagnostic differentiation from CLL disease progression, Richter's transformation to aggressive lymphoma, and secondary malignancy relies on histological and appropriate microbiological studies from biopsy material of affected organs. Infection prophylaxis in CLL should be considered, including vaccinations and intravenous immune globulin replacement.
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http://dx.doi.org/10.3390/jcm8020216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406768PMC
February 2019

Anti-inflammatory therapy in well controlled HIV infection.

Lancet HIV 2018 10 23;5(10):e538-e539. Epub 2018 Sep 23.

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

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http://dx.doi.org/10.1016/S2352-3018(18)30250-9DOI Listing
October 2018

Interferon lambda 3/4 polymorphisms are associated with AIDS-related Kaposi's sarcoma.

AIDS 2018 11;32(18):2759-2765

Infectious Diseases Service, Department of Medicine.

Background: Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections.

Objectives: To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS).

Methods: The risk of developing Kaposi's sarcoma according to the carriage of IFNL3/4 SNPs rs8099917 and rs12980275 and their haplotypic combinations was assessed by using cumulative incidence curves and Cox regression models, accounting for relevant covariables.

Results: Kaposi's sarcoma was diagnosed in 221 of 2558 MSM Caucasian SHCS participants. Both rs12980275 and rs8099917 were associated with an increased risk of Kaposi's sarcoma (cumulative incidence 15 versus 10%, P = 0.01 and 16 versus 10%, P = 0.009, respectively). Diplotypes predicted to produce the active P70 form (cumulative incidence 16 versus 10%, P = 0.01) but not the less active S70 (cumulative incidence 11 versus 10%, P = 0.7) form of IFNL4 were associated with an increased risk of Kaposi's sarcoma, compared with those predicted not to produce IFNL4. The associations remained significant in a multivariate Cox regression model after adjustment for age at infection, combination antiretroviral therapy, median CD4+ T-cell count nadir and CD4+ slopes (hazard ratio 1.42, 95% confidence interval 1.06-1.89, P = 0.02 for IFLN P70 versus no IFNL4).

Conclusion: This study reports for the first time an association between IFNL3/4 polymorphisms and susceptibility to AIDS-related Kaposi's sarcoma.
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http://dx.doi.org/10.1097/QAD.0000000000002004DOI Listing
November 2018

Corrigendum to "Alveolar echinococcosis: From a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years" [J Hepatol 49 (2008) 72-77].

J Hepatol 2018 Nov 8;69(5):1208. Epub 2018 Sep 8.

Gastroenterology and Hepatology, University Hospital of Zürich, Rämistrasse 100, Zürich CH-8091, Switzerland; Swiss HBP Center, University Hospital of Zürich, Rämistrasse 100, Zürich CH-8091, Switzerland. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2018.08.010DOI Listing
November 2018

HIV and Aging - Perhaps Not as Dramatic as We Feared?

Gerontology 2018 15;64(5):446-456. Epub 2018 Jun 15.

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

Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to "metabolic" complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims of this viewpoint paper are to summarize recent data and to examine the possibility that the problem of aging-related morbidity in HIV might not be as dramatic as previously believed.
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http://dx.doi.org/10.1159/000489172DOI Listing
December 2018

Incidental Findings on Coronary Computed Tomography Angiography in Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Persons.

Open Forum Infect Dis 2018 May 20;5(5):ofy084. Epub 2018 Apr 20.

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

Background: Incidental findings on coronary computed tomography angiography (CCTA) have a great impact on the benefits and costs of testing for cardiovascular disease. The number of incidental findings might be increased in human immunodeficiency virus (HIV)-positive individuals compared with the general population. Data are limited regarding the association between incidental findings and HIV infection.

Methods: We assessed the prevalence and factors associated with incidental findings among HIV-positive and HIV-negative participants ≥45 years undergoing CCTA. Logistic regression was performed to evaluate the factors associated with incidental findings in the HIV-positive and HIV-negative groups. For the analysis of the HIV effect, a propensity score-matched dataset of HIV-positive/HIV-negative participants was used.

Results: We included 553 participants, 341 with and 212 without HIV infection. Incidental findings were observed in 291 of 553 (53%) patients. In 42 of 553 (7.6%) participants, an incidental finding resulted in additional workup. A malignancy was diagnosed in 2 persons. In the HIV-positive group, age (1.31 per 5 years, 1.10-1.56) and smoking (2.29, 1.43-3.70) were associated with incidental findings; in the HIV-negative group, age (1.26, 1.01-1.59) and a CAC score >0 (2.08, 1.09-4.02) were associated with incidental findings. Human immunodeficiency virus seropositivity did not affect the risk of incidental findings.

Conclusions: Incidental findings were highly prevalent among HIV-positive and HIV-negative persons. Human immunodeficiency virus infection was not associated with an increased risk of incidental findings.
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http://dx.doi.org/10.1093/ofid/ofy084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952950PMC
May 2018
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