Publications by authors named "Wyen C"

Article Synopsis
  • The study aimed to evaluate how well the Veterans Aging Cohort Study (VACS) Index 2.0 predicts specific causes of death in people with HIV (PWH) receiving antiretroviral therapy (ART), which could improve targeted healthcare interventions.
  • It involved analyzing data from over 59,000 PWH who started ART between 2000 and 2018, calculating their VACS scores and examining the relationship between these scores and causes of death through various statistical models.
  • Findings revealed that the VACS Index 2.0 was particularly effective at predicting deaths from AIDS-related causes and other measurable health issues, but less reliable for predicting suicides or accidental deaths.
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Results of a prospective study of stage-adapted treatment of human immunodeficiency virus (HIV)-associated Hodgkin lymphoma (HIV-HL) showed a 2-year overall survival (OS) of 90.7% with no significant difference between early favorable (EF), early unfavorable (EU), and advanced HL. Patients with EF HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy involved field (IF) radiation, those with EU HIV-HL received four cycles of ABVD or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline + 30 Gy IF, and six to eight cycles of BEACOPP baseline were administered in advanced disease.

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Cryptococcosis is the most prevalent fungal infection of the central nervous system worldwide. We performed a retrospective multicenter cohort study to gain insights into the epidemiology of cryptococcosis in Germany. We describe the use of diagnostic tests, clinical management and patient outcome.

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Background: Switching to the 2-drug regimen dolutegravir/lamivudine demonstrated durable non-inferior efficacy vs continuing 3- or 4-drug tenofovir alafenamide-based regimens for maintaining virologic suppression in people with HIV-1 through Week 144 in TANGO.

Setting: 134 centers, 10 countries.

Methods: Adults with HIV-1 RNA <50 copies/mL for >6 months and no history of virologic failure were randomized to switch from stable tenofovir alafenamide-based regimens to dolutegravir/lamivudine on Day 1 (early-switch group) for 196 weeks.

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Background: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

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Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART).

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The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department.

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Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART).

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Objectives: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose).

Methods: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits.

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Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients' disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age.

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Background: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV.

Methods: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022.

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Article Synopsis
  • NK cells are crucial for fighting viral infections and use a variety of receptors, with HLA-C being the main ligand for Killer-cell immunoglobulin-like receptors (KIRs), influencing NK cell activity.
  • The study shows that HIV-1 can evade the immune response by adapting to host genetics, particularly through the Vpu protein that downregulates HLA-C, which helps the virus escape detection by NK cells.
  • Researchers found that HIV-1 infection leads to changes in the NK cell receptor profile, including an increase in specific NK cell populations and a genotype-dependent expansion of KIR2DL1, indicating a complex relationship between the immune response and HIV-1 evolution.
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Article Synopsis
  • - TANGO study found that switching to dolutegravir/lamivudine (DTG/3TC) was as effective as maintaining tenofovir alafenamide (TAF)-based regimens for HIV-1 treatment after 144 weeks, with only 0.3% of DTG/3TC participants showing viral rebound compared to 1.3% on TAF.
  • - Safety profiles indicated more drug-related side effects with DTG/3TC, particularly in the first 48 weeks (15% adverse events vs. 5% for TAF), but rates became similar afterward.
  • - Overall, DTG/3TC was associated with favorable changes in lipid levels and showed no significant impact
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Despite available vaccinations COVID-19 case numbers around the world are still growing, and effective medications against severe cases are lacking. In this work, we developed a machine learning model which predicts mortality for COVID-19 patients using data from the multi-center 'Lean European Open Survey on SARS-CoV-2-infected patients' (LEOSS) observational study (>100 active sites in Europe, primarily in Germany), resulting into an AUC of almost 80%. We showed that molecular mechanisms related to dementia, one of the relevant predictors in our model, intersect with those associated to COVID-19.

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Article Synopsis
  • HIV-1 forms a latent reservoir in CD4+ T cells, making it hard to completely eliminate the virus with antiretroviral therapy (ART).
  • A study found that combining dasatinib treatment for chronic myeloid leukemia (CML) with ART in HIV-infected patients significantly reduced the size and reactivation of this viral reservoir.
  • Results showed that patients on both treatments had a more than 5-fold decrease in latently infected cells and over 4-fold reduction in reactivated proviruses, suggesting that dasatinib could enhance HIV treatment outcomes.
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Background: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries.

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Objectives: Non-treponemal serological tests are used to monitor treatment response during syphilis infection. Syphilis- and HIV-coinfected patients may experience incomplete resolution in non-treponemal titres, which is referred to as the serofast state. The goal of this study was to evaluate risk factors for serofast state in HIV-infected patients.

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Background: Dolutegravir (DTG) and boosted darunavir (bDRV) are potent antiretrovirals with a high resistance barrier and might be valuable switch options for people with HIV (PWH).

Methods: DUALIS, a randomized, open-label, phase 3b, noninferiority clinical trial, compared the switch to DTG + bDRV (2DR) with continuation of 2 nucleoside reverse transcriptase inhibitors (2NRTI) + bDRV (3DR). PWH with HIV RNA <50 copies/mL taking 2NRTI + bDRV (3DR) for ≥24 weeks (1 accepted blip <200 copies/mL) were randomized to either switch to DTG 50 mg + DRV 800 mg (boosted with 100 mg of ritonavir) or continue taking 3DR.

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Purpose: Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany.

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People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer.

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Background: The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals.

Methods: TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)-based regimen.

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Article Synopsis
  • The study analyzed HIV cohort data from high-income European countries to compare mortality rates and excess mortality estimates for people living with HIV on antiretroviral therapy (ART) using UNAIDS Spectrum modeling parameters.
  • Data from 2000 to 2015 revealed that all-cause mortality rates decreased over time in both the Spectrum and ART-CC datasets, with AIDS-related deaths also declining significantly.
  • The findings suggest that mortality assumptions for people living with HIV on ART should be revised in the Spectrum model, indicating higher rates in earlier years (2000-2003) that decline more rapidly into recent years.
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Background: Safety and tolerability of analytical treatment interruptions (ATIs) as a vital part of human immunodeficiency virus type 1 (HIV-1) cure studies are discussed. We analyzed current evidence for the occurrence of adverse events (AEs) during TIs.

Methods: Our analysis included studies that reported on AEs in HIV-1-infected patients undergoing TIs.

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