Publications by authors named "Patrick Schmid"

86 Publications

Response to a sexual risk reduction intervention provided in combination with hepatitis C treatment by HIV/HCV co-infected men who have sex with men: a reflexive thematic analysis.

BMC Infect Dis 2021 Apr 6;21(1):319. Epub 2021 Apr 6.

Nursing Science, Department Public Health, Medical Faculty, University of Basel, Basel, Switzerland.

Background: Hepatitis C virus reinfections in HIV-positive men-who-have-sex-with-men (MSM) challenge the effectiveness of antiviral treatment. To fight this problem, an adapted sexual risk reduction intervention was implemented within a hepatitis C treatment trial. Following this, the current study had two aims and describes 1) how the program was received by participants; and 2) their responses to the program regarding sexual risk taking. Based on the participants' input, we hoped to judge the intervention's potential for scale-up.

Methods: Seventeen participants who received the sexual risk reduction intervention in addition to hepatitis C treatment were recruited for semi-structured interviews six to 12 months post-intervention. We evaluated the responses via reflexive thematic analysis and applied the concept of sense-making.

Results: Giving hepatitis C a place and living without it again illustrates how participants received the program and how their experiences were altered by the impact of sense-making. Based on their responses, we allocated participants to three groups: 1. Avoid risks: get rid of hepatitis C for life. For these men, hepatitis C remained a life-threatening disease: they actively modified their risk behavior and felt supported by the intervention in maintaining their behavioral changes. 2. Minimize risks: live as long as possible without hepatitis C. In contrast to group 1, these men saw hepatitis C as a manageable disease. The intervention facilitated reflection on risks and how to develop behavioral changes that suited them individually. 3. Accept risks; live with the risk of hepatitis C. These men perceived behavioral changes as much more difficult than "easy" medical treatment. They expected to either undergo repeated rounds of treatment or stay HCV re-infected.

Conclusion: These results illustrate the diversity of men's responses and their decisions regarding sexual risk behavior after participating in a combination of antiviral treatment and a sexual risk reduction intervention. Two major aspects were identified: 1) Teachable moments, particularly at the time of diagnosis/treatment, could offer an opportunity to develop openness for behavioral change; 2) adapting sexual risk reduction interventions to sense-making patterns could help to improve its effectiveness. Support for reducing infection risk and raising awareness of preventative measures are additional benefits.

Trial Registration: Clinical Trial Number: NCT02785666 , 30.05.2016.
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http://dx.doi.org/10.1186/s12879-021-06003-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022541PMC
April 2021

Pharmacokinetic parameters and weight change in HIV patients newly switched to dolutegravir-based regimens in SIMPL'HIV clinical trial.

Br J Clin Pharmacol 2021 Mar 25. Epub 2021 Mar 25.

HIV/AIDS Unit, Department of Infectious Diseases, Geneva University Hospitals and the University of Geneva Faculty of Medicine, Geneva, Switzerland.

This study aims to evaluate the association between dolutegravir (DTG) pharmacokinetic parameters and weight changes in treatment-experienced people with HIV (PWHIV) from the Simpl'HIV study newly switched to a dual DTG-based regimen. We used multivariable linear regressions to evaluate the association between DTG pharmacokinetic parameters at week 48 (derived using an established model) and weight change between week 0 and week 48. We adjusted our model for potential confounders including CD4 nadir, female sex, African origin, age, weight at week 0 and presence of a non-nucleoside reverse transcriptase inhibitor-based regimen before switch to DTG. The analysis included data from 39 PWHIV. An average significant weight gain of 2.4 kg was observed between baseline and week 48. DTG plasma exposure was not significantly associated with weight gain, even after adjusting for potential confounders (P = .9). We found no significant association between DTG pharmacokinetic parameters and weight gain amongst PWHIV newly switched to a DTG-based dual regimen.
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http://dx.doi.org/10.1111/bcp.14832DOI Listing
March 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 Mar 16. 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
March 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
March 2021

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

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

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

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

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

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

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

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

Increased CHIP Prevalence Amongst People Living with HIV.

medRxiv 2020 Nov 7. Epub 2020 Nov 7.

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n=600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n=8,111) from blood DNA-derived exome sequences. We observed that HIV is associated with increased CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p=0.005). Additionally, unlike in ARIC, ASXL1 was the most commonly implicated mutated CHIP gene. We propose that CHIP may be one mechanism through which PLWH are at increased risk for CAD. Larger prospective studies should evaluate the hypothesis that CHIP contributes to the excess cardiovascular risk in PLWH.
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http://dx.doi.org/10.1101/2020.11.06.20225607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654930PMC
November 2020

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

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

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

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

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

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

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

Rapid Progression of Kidney Dysfunction in Swiss People Living with HIV: Contribution of Polygenic Risk Score and D:A:D Clinical Risk Score.

J Infect Dis 2020 Nov 5. Epub 2020 Nov 5.

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

Background: In people with HIV (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction; i.e. eGFR decrease of >5mL/min/1.73m 2 per year for >3 consecutive years.

Methods: We used time-to-event analyses to measure univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D CKD risk score, antiretroviral exposures, and a polygenic risk score based on 14'769 genome-wide single nucleotide polymorphisms (SNPs) in white Swiss HIV Cohort Study participants.

Results: We included 225 participants with rapid progression (median age 42 years, 76% male, median baseline eGFR 101 mL/min/1.73m 2) and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with a low risk D:A:D CKD risk score, participants with medium and high risk had rapid progression-HR=1.30 (0.99-1.71) and 1.82 (1.28-2.60), respectively. Compared to the first (most favorable) polygenic risk score quartile, participants in the second, third and fourth (most unfavorable) quartiles had rapid progression-HR=1.39 (0.94-2.06), 1.52 (1.04-2.24) and 2.04 (1.41-2.94), respectively. Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR=1.36 [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
November 2020

Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment.

J Acquir Immune Defic Syndr 2020 12;85(4):517-524

School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Background: The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here, we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment.

Setting: Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study, a nation-wide prospective observational study.

Methods: We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size at 3 time points over a median of 5.4 years, and searched for associations between human genetic variation and 2 phenotypic readouts: the reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.

Results: Genome-wide and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive antiretroviral treatment.

Conclusions: Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.
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http://dx.doi.org/10.1097/QAI.0000000000002473DOI Listing
December 2020

Brief Report: Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction-A Prospective Cohort Study.

J Acquir Immune Defic Syndr 2020 10;85(2):227-232

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

Background: Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear.

Methods: We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series.

Results: Among 106 participants (15.1% women, median age 53 years), eGFR was 60-89 mL/min/1.73 m in 84 (79.2%) and <60 mL/min/1.73 m in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m experienced increases in eGFR of 3.2 mL/min/1.73 m (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m experienced improvements of 6.2 mL/min/1.73 m (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (-6.3 mg/mmol, 95% CI -10.0 to -2.7), and ALT levels declined in patients with elevated baseline levels (-11.8 IU/L, 95% CI -17.3 to -6.4) 1 year after replacing TDF with TAF.

Conclusions: Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels.
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http://dx.doi.org/10.1097/QAI.0000000000002429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495978PMC
October 2020

All-Cause Mortality and Causes of Death in the Swiss Hepatitis C Cohort Study (SCCS).

Open Forum Infect Dis 2020 Aug 25;7(8):ofaa308. Epub 2020 Jul 25.

Institute of Global Health, University of Geneva, Geneva, Switzerland.

Background: With direct-acting antiviral agents (DAAs), mortality rates and causes of death among persons with hepatitis C virus (HCV) infection may change over time. However, the emergence of such trends may be delayed by the slow progression of chronic hepatitis C. To date, detailed analyses of cause-specific mortality among HCV-infected persons over time remain limited.

Methods: We evaluated changes in causes of death among Swiss Hepatitis C Cohort Study (SCCS) participants from 2008 to 2016. We analyzed risk factors for all-cause and cause-specific mortality, accounting for changes in treatment, fibrosis stage, and use of injectable drugs over time. Mortality ascertainment was completed by linking lost-to-follow-up participants to the Swiss Federal Statistical Office death registry.

Results: We included 4700 SCCS participants, of whom 478 died between 2008 and 2016. The proportion of unknown causes of death decreased substantially after linkage, from 42% to 10%. Leading causes of death were liver failure (crude death rate 4.4/1000 person-years), liver cancer (3.4/1000 person-years), and nonliver cancer (2.8/1000 person-years), with an increasing proportion of cancer-related deaths over time. Cause-specific analysis showed that persons with sustained virologic response were less at risk for liver-related mortality than those never treated or treated unsuccessfully.

Conclusions: Although the expected decrease in mortality is not yet observable, causes of death among HCV-infected persons have evolved over time. With the wider use of DAAs, liver-related mortality is expected to decline in the future. Continued monitoring of cause-specific mortality will remain important to assess the long-term effect of DAAs and design effective interventions.
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http://dx.doi.org/10.1093/ofid/ofaa308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443104PMC
August 2020

A treatment as prevention trial to eliminate hepatitis C among men who have sex with men living with HIV in the Swiss HIV Cohort Study.

Clin Infect Dis 2020 Aug 6. Epub 2020 Aug 6.

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

Background: In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with HIV from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population.

Methods: During phase A (10/2015-06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016-02/2017) we offered treatment with HCV direct-acting agents (DAAs) to MSM identified with a replicating HCV infection. During phase C (03/2017-11/2017), we offered re-screen to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections (Clinicaltrials.gov NCT02785666).

Findings: We screened 3'715/4'640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of which started DAA treatment and 149 (99.3%) were cured. We re-screened 2'930/3'538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from 0.53 per 100 patient-years (95% confidence interval [CI] 0.35, 0.83) prior to the intervention to 0.12 (CI 0.03, 0.49) by the end of 2019.

Interpretation: A systematic and population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets.
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http://dx.doi.org/10.1093/cid/ciaa1124DOI Listing
August 2020

Genetic variation near CXCL12 is associated with susceptibility to HIV-related non-Hodgkin lymphoma.

Haematologica 2020 07 16. Epub 2020 Jul 16.

Ecole Polytechnique Federale de Lausanne and University of Lausanne, Switzerland

Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.
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http://dx.doi.org/10.3324/haematol.2020.247023DOI Listing
July 2020

Changes in Renal Function After Switching From TDF to TAF in HIV-Infected Individuals: A Prospective Cohort Study.

J Infect Dis 2020 07;222(4):637-645

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

Background: Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) improves renal tubular markers in HIV-infected individuals but the impact on estimated glomerular filtration rate (eGFR) remains unclear.

Methods: In all participants from the Swiss HIV Cohort Study who switched from TDF to TAF-containing antiretroviral regimen or continued TDF, we estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months using mixed-effect models.

Results: Of 3520 participants (26.6% women, median age 50 years), 2404 (68.5%) switched to TAF. Overall, 1664 (47.3%) had an eGFR <90 mL/min and 1087 (30.9%) an UPCR ≥15 mg/mmol. In patients with baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (-1.7 mL/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% confidence interval [CI], .5-2.5) if the baseline eGFR was 60-89 mL/min, and 4.1 mL/min (95% CI, 1.6-6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI, 2.3-9.3) with continued use of TDF in individuals with baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR.

Conclusions: Switching from TDF to TAF improves eGFR and proteinuria in patients with renal dysfunction.
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http://dx.doi.org/10.1093/infdis/jiaa125DOI Listing
July 2020

Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients.

Open Forum Infect Dis 2019 Oct 12;6(10):ofz330. Epub 2019 Jul 12.

Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Switzerland.

Objective: The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated.

Method: This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population.

Results: We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154-441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4-21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35-4.59 and HR 1.66; 95% CI, 0.81-3.43, respectively).

Conclusions: In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.
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http://dx.doi.org/10.1093/ofid/ofz330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778427PMC
October 2019

Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients.

Open Forum Infect Dis 2019 Oct 12;6(10):ofz330. Epub 2019 Jul 12.

Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Switzerland.

Objective: The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated.

Method: This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population.

Results: We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154-441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2-79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4-21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35-4.59 and HR 1.66; 95% CI, 0.81-3.43, respectively).

Conclusions: In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.
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http://dx.doi.org/10.1093/ofid/ofz330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778427PMC
October 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 Jul;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

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

Very Low Hepatitis C Viral Loads in Treatment-naive Persons: Do They Compromise Hepatitis C Virus Antigen Testing?

Clin Infect Dis 2020 02;70(4):653-659

Institute of Global Health, University of Geneva, Zürich.

Background: Hepatitis C virus (HCV) antigen testing is less expensive than quantitative reverse-transcription polymerase chain reaction but has lower sensitivity for very low viral load (VLVL; HCV RNA ≤3000 IU/mL). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce.

Methods: We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing.

Results: We included 2533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female sex, and human immunodeficiency virus coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall, 33% of samples with VLVL were reactive by antigen testing.

Conclusions: The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.
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http://dx.doi.org/10.1093/cid/ciz270DOI Listing
February 2020

Very Low Hepatitis C Viral Loads in Treatment-naive Persons: Do They Compromise Hepatitis C Virus Antigen Testing?

Clin Infect Dis 2020 02;70(4):653-659

Institute of Global Health, University of Geneva, Zürich.

Background: Hepatitis C virus (HCV) antigen testing is less expensive than quantitative reverse-transcription polymerase chain reaction but has lower sensitivity for very low viral load (VLVL; HCV RNA ≤3000 IU/mL). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce.

Methods: We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing.

Results: We included 2533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female sex, and human immunodeficiency virus coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall, 33% of samples with VLVL were reactive by antigen testing.

Conclusions: The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.
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http://dx.doi.org/10.1093/cid/ciz270DOI Listing
February 2020

Emergence of Drug Resistance in the Swiss HIV Cohort Study Under Potent Antiretroviral Therapy Is Observed in Socially Disadvantaged Patients.

Clin Infect Dis 2020 01;70(2):297-303

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich.

Background: The rate of acquired human immunodeficiency virus type 1 (HIV-1) drug resistance (ADR) has fallen dramatically since introduction of combined antiretroviral therapy (cART) in Switzerland. However, clinical experience indicates that there are still patients at risk of newly acquiring drug resistance despite having access to cART. Here, we characterized risk factors for ADR, to improve patient care and prevent emergence of drug resistance and treatment failure.

Methods: We performed a case-control study to identify risk factors for ADR in all patients starting their first cART in the Swiss HIV Cohort Study (SHCS) since 1996. The SHCS is highly representative and includes >75% of patients receiving ART in Switzerland. To this end, we implemented a systematic medical chart review to obtain more detailed information on additional parameters, which are not routinely collected in the SHCS. The collected data were analyzed using univariable and multivariable conditional logistic regression.

Results: We included in our study 115 cases and 115 matched controls. Unemployment (multivariable odds ratio [mOR], 2.9 [95% confidence interval {CI}, 1.3-6.4]; P = .008), African origin (mOR, 3.0 [95% CI, 1.0-9.2]; P = .047), comedication with anti-infectives (mOR, 3.7 [95% CI, 1.0-12.6]; P = .045), and symptoms of mental illness (mOR, 2.6 [95% CI, 1.2-5.5]; P = .012) were associated with ADR in the multivariable model.

Conclusions: Although ADR has become very rare with cART due to new potent therapies, patients in socially challenging life situations or presenting with mental health issues are at higher risk for drug resistance. Prompt identification and adequate support of these patients before ADR will prevent treatment failure and HIV-1 transmission.
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http://dx.doi.org/10.1093/cid/ciz178DOI Listing
January 2020

Paritaprevir, ritonavir, ombitasvir, and dasabuvir with and without ribavirin in people with HCV genotype 1 and recent injecting drug use or receiving opioid substitution therapy.

Int J Drug Policy 2018 12 29;62:94-103. Epub 2018 Oct 29.

The Kirby Institute, UNSW Sydney, Wallace Wurth Building, UNSW NSW 2052, Australia.

Background: Direct-acting antiviral therapy for hepatitis C virus (HCV) infection is safe and effective, but there are little data among people who have recently injected drugs. This study evaluated the efficacy, and safety of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for chronic HCV genotype (G) 1 among people with recent injecting drug use and/or receiving OST.

Methods: D3FEAT is an international open-label study that recruited treatment-naïve participants with recent injecting drug use (previous 6 months) and/or receiving OST with chronic HCV G1 infection between June 2016 and February 2017 in seven countries. Participants received paritaprevir/ritonavir, ombitasvir, dasabuvir with (G1a) or without ribavirin (G1b) administered twice daily in a one-week electronic blister pack (records timing of each dose) for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (SVR12).

Results: Among 87 participants (median age 48 years), 23% were female, 8% had cirrhosis, and 90% had G1a. Overall, 71% were receiving OST, 61% injected in the previous six months, 45% injected in the previous month, and 15% injected > daily. Treatment completion was 97% (84 of 87). There were no virological breakthroughs, but three discontinuations (loss to follow-up, n = 1; non-adherence, n = 1; incarceration, n = 1). SVR was 91% (79 of 87, 95% CI, 83%-96%). Five participants who completed treatment did not have SVR (loss to follow-up, n = 1; death, n = 1; virologic relapse, n = 3). Drug use prior to and during treatment did not impact SVR12. Treatment-related adverse events were observed in 46 (53%) patients (six grade 3, no grade 4). Five (6%) patients had at least one serious adverse event (two possibly/probably related to therapy; nausea and myoclonus). Two cases of reinfection were observed.

Conclusion: Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for 12 weeks is effective among people with HCV genotype 1 with recent injecting drug use and/or receiving OST.
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http://dx.doi.org/10.1016/j.drugpo.2018.10.004DOI Listing
December 2018

Variation in antiretroviral treatment coverage and virological suppression among three HIV key populations.

AIDS 2018 11;32(18):2807-2819

CHIP, Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Objectives: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use (IDU) and heterosexual transmission.

Design: A multinational cohort study.

Methods: Within the EuroSIDA study, we assessed region-specific percentages of ART-coverage among those in care and virological suppression (<500 copies/ml) among those on ART, and analysed differences between transmission categories using logistic regression.

Results: Among 12 872 participants followed from 1 July 2014 to 30 June 2016, the percentages of ART-coverage and virological suppression varied between transmission categories, depending on geographical region (global P for interaction: P = 0.0148 for ART-coverage, P = 0.0006 for virological suppression). In Western [adjusted odds ratio (aOR) 1.41 (95% confidence interval 1.14-1.75)] and Northern Europe [aOR 1.68 (95% confidence interval 1.25-2.26)], heterosexuals were more likely to receive ART than MSM, while in Eastern Europe, there was some evidence that infection through IDU [aOR 0.60 (95% confidence interval 0.31-1.14)] or heterosexual contact [aOR 0.58 (95% confidence interval 0.30-1.10)] was associated with lower odds of receiving ART. In terms of virological suppression, people infected through IDU or heterosexual contact in East Central and Eastern Europe were around half as likely as MSM to have a suppressed viral load on ART, while we observed no differences in virological suppression across transmission categories in Western and Northern Europe.

Conclusion: In our cohort, patterns of ART-coverage and virological suppression among key populations varied by geographical region, emphasizing the importance of tailoring HIV programmes to the local epidemic.
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http://dx.doi.org/10.1097/QAD.0000000000002035DOI Listing
November 2018

Population-based outcome analysis of diffuse large B-cell lymphoma in people living with HIV infection and competent individuals.

Hematol Oncol 2018 Dec 16;36(5):757-764. Epub 2018 Aug 16.

Division of Infectious Diseases, Ospedale Regionale di Lugano, Lugano, Switzerland.

The prognostic factors and outcome of 58 acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AR-DLBCL) patients from the Swiss HIV Cohort Study, diagnosed from 2004 to 2011, were compared with those of 326 immunocompetent (IC)-DLBCL from the Hematology Division of the Amedeo Avogadro University (Italy) and the Oncology Institute of Southern Switzerland. Median follow-up was 6 years; 5-year overall survival (OS) was 68% (95% CI: 63%-73%) in IC-DLBCL and 63% (95% CI: 49%-75%) in AR-DLBCL (P = .220). The acquired immunodeficiency syndrome-related lymphoma international prognostic index predicted OS in AR-DLBCL. Among 148 patients younger than 61 years (40 AR-DLBCL and 108 IC-DLBCL) treated with RCHOP/RCHOP-like regimens, 20 IC-DLBCL and 9 AR-DLBCL patients died and OS was not significantly different. A higher proportion of early deaths occurred in the AR-DLBCL: indeed, 1-year OS was 94% (95% CI: 87%-97%) in IC-DLBCL and 82% (95% CI: 66%-91%) in AR-DLBCL patients. After rituximab and active antiretroviral therapy introduction, AR-DLBCL and IC-DLBCL patients treated with curative intent have similar long-term survival.
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http://dx.doi.org/10.1002/hon.2536DOI Listing
December 2018

High Number of Potential Transmitters Revealed in a Population-based Systematic Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men Who Have Sex With Men.

Clin Infect Dis 2019 02;68(4):561-568

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

Background: The proportion of undiagnosed hepatitis C virus (HCV) infections in high-risk populations, such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) is unclear. Identification of potential HCV transmitters is important to reach World Health Organization HCV elimination targets.

Methods: Between October 2015 and May 2016, we performed a systematic HCV RNA-based screening among HIV-infected MSM participating in the Swiss HIV Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA-positive samples.

Results: Of 4257 MSM recorded in the SHCS database, we screened 3722 (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV infection. We identified 24 individuals (14%) with incident HCV infection; one-third of them had a negative HCV antibody result at the time of HCV RNA positivity. In a multivariable model, elevated liver enzyme values (odds ratio, 14.52; 95% confidence interval, 9.92-21.26), unprotected sex with occasional partners (2.01; 1.36-2.98), intravenous drug use (7.13; 4.36-11.64), noninjectable drug use (1.94; 1.3-2.88), and previous syphilis diagnosis (2.56; 1.74-3.76) were associated with HCV RNA positivity.

Conclusions: A systematic HCV RNA-based screening among HIV-infected MSM revealed a high number of potential transmitters. A substantial subpopulation of MSM had incident infection, one-third of whom had a negative HCV antibody test result at the time of the HCV RNA positivity. These data reveal that one-time RNA testing of a high-risk population for HCV RNA might identify more infected persons than routine testing for HCV antibodies and liver enzymes.

Clinical Trials Registration: NCT02785666.
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http://dx.doi.org/10.1093/cid/ciy545DOI Listing
February 2019

High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus-coinfected Men Who Have Sex With Men.

Clin Infect Dis 2019 02;68(4):569-576

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

Background: This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial.

Methods: We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a-infected individuals with baseline RASs and genotype 4-infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction-oriented behavioral intervention.

Results: We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program.

Conclusions: Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a-infected individuals, and the treatment phase was accompanied by an HCV risk reduction-oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM.

Clinical Trials Registration: NCT02785666.
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http://dx.doi.org/10.1093/cid/ciy547DOI Listing
February 2019

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