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Artikel ; Online: HIV Gag and PR

Nijhuis Monique

Retrovirology, Vol 8, Iss Suppl 2, p O

partners in resistance to protease and maturation inhibitors

2011 Band 40

Schlagwörter	Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Immunologic diseases. Allergy ; RC581-607
Sprache	Englisch
Erscheinungsdatum	2011-10-01T00:00:00Z
Verlag	BioMed Central
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel: Crosstalk between TLR8 and RIG-I-like receptors enhances antiviral immune responses.

Vlaming, Killian E / van Wijnbergen, Kelly / Kaptein, Tanja M / Nijhuis, Monique / Kootstra, Neeltje J / de Bree, Godelieve J / Geijtenbeek, Teunis B

Frontiers in medicine

2023 Band 10, Seite(n) 1146457

Abstract: Background: Toll-like receptor (TLR) agonists have been investigated due to their potential dual effects as latency reverting agents and immune modulatory compounds in people living with HIV (PLWH). Here, we investigated whether co-stimulation of TLR7/8 ...

Abstract	Background: Toll-like receptor (TLR) agonists have been investigated due to their potential dual effects as latency reverting agents and immune modulatory compounds in people living with HIV (PLWH). Here, we investigated whether co-stimulation of TLR7/8 agonists with RIG-I-like receptor (RLR) agonists enhances antiviral immunity. Methods: Peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (DCs) were incubated with TLR and RLR-agonists for 24 h and innate and adaptive immune responses were determined (maturation markers, cytokines in supernatant, ISG expression). Results: Both TLR7 and TLR8 agonists induced pro-inflammatory cytokines in DCs as well as PBMCs. TLR8 agonists were more potent in inducing cytokine responses and had a stronger effect on DC-induced immunity. Notably, while all compounds induced IL-12p70, co-stimulation with TLR8 agonists and RLR agonist polyI: C induced significantly higher levels of IL-12p70 in PBMCs. Moreover, crosstalk between TLR8 and RLR agonists induced a strong type I Interferon (IFN) response as different antiviral IFN-stimulated genes were upregulated by the combination compared to the agonists alone. Conclusion: Our data strongly suggest that TLR crosstalk with RLRs leads to strong antiviral immunity as shown by induction of IL-12 and type I IFN responses in contrast to TLRs alone. Thus, co-stimulation of TLRs and RLRs might be a powerful strategy to induce reactivation of latent reservoir as well as antiviral immunity that eliminates the reactivated cells.
Sprache	Englisch
Erscheinungsdatum	2023-05-16
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1146457
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Evaluation of a commercial SARS-CoV-2 multiplex PCR genotyping assay for variant identification in resource-scarce settings.

Umunnakwe, Chijioke N / Makatini, Zinhle N / Maphanga, Mathapelo / Mdunyelwa, Anele / Mlambo, Khamusi M / Manyaka, Puseletso / Nijhuis, Monique / Wensing, Annemarie / Tempelman, Hugo A

PloS one

2022 Band 17, Heft 6, Seite(n) e0269071

Abstract: The rapid emergence and spread of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants across the globe underscores the crucial need for continuous SARS-CoV-2 surveillance to ensure that potentially more pathogenic variants are ... ...

Abstract	The rapid emergence and spread of numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants across the globe underscores the crucial need for continuous SARS-CoV-2 surveillance to ensure that potentially more pathogenic variants are detected early and contained. Whole genome sequencing (WGS) is currently the gold standard for COVID-19 surveillance; however, it remains cost-prohibitive and requires specialized technical skills. To increase surveillance capacity, especially in resource-scarce settings, supplementary methods that are cost- and time-effective are needed. Real-time multiplex PCR genotyping assays offer an economical and fast solution for screening circulating and emerging variants while simultaneously complementing existing WGS approaches. In this study we evaluated the AllplexTM SARS-CoV-2 Variants II multiplex real-time PCR genotyping assay, Seegene (South Korea), and implemented it in retrospectively characterizing circulating SARS-CoV-2 variants in a rural South African setting between April and October 2021, prior to the emergence of the Omicron variant in South Africa. The AllplexTM SARS-CoV-2 Variants II real-time PCR assay demonstrated perfect concordance with whole-genome sequencing in detecting Beta and Delta variants and exhibited high specificity, sensitivity and reproducibility. Implementation of the assay in characterization of SARS-CoV-2 variants between April and October 2021 in a rural South African setting revealed a rapid shift from the Beta to the Delta variant between April and June. All specimens successfully genotyped in April were Beta variants and the Delta variant was not detected until May. By June, 78% of samples genotyped were Delta variants and in July >95% of all genotyped samples were Delta variants. The Delta variant continued to predominate through to the end of our analysis in October 2021. Taken together, a commercial SARS-CoV-2 variant genotyping assay detected the rapid rate at which the Delta variant displaced the Beta variant in Limpopo, an under-monitored province in South Africa. Such assays provide a quick and cost-effective method of monitoring circulating variants and should be used to complement genomic sequencing for COVID-19 surveillance especially in resource-scarce settings.
Mesh-Begriff(e)	COVID-19/diagnosis ; Genotype ; Humans ; Multiplex Polymerase Chain Reaction ; Reproducibility of Results ; Retrospective Studies ; SARS-CoV-2/genetics
Sprache	Englisch
Erscheinungsdatum	2022-06-24
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0269071
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Characterization of HIV variants from paired Cerebrospinal fluid and Plasma samples in primary microglia and CD4

Gumbs, Stephanie B H / Stam, Arjen J / Mudrikova, Tania / Schipper, Pauline J / Hoepelman, Andy I M / van Ham, Petra M / Borst, Anne L / Hofstra, LMarije / Gharu, Lavina / van Wyk, Stephanie / Wilkinson, Eduan / de Witte, Lot D / Wensing, Annemarie M J / Nijhuis, Monique

Journal of neurovirology

2024

Abstract: Despite antiretroviral therapy (ART), HIV persistence in the central nervous system (CNS) continues to cause a range of cognitive impairments in people living with HIV (PLWH). Upon disease progression, transmigrating CCR5-using T-cell tropic viruses are ... ...

Abstract	Despite antiretroviral therapy (ART), HIV persistence in the central nervous system (CNS) continues to cause a range of cognitive impairments in people living with HIV (PLWH). Upon disease progression, transmigrating CCR5-using T-cell tropic viruses are hypothesized to evolve into macrophage-tropic viruses in the CNS that can efficiently infect low CD4-expressing cells, such as microglia. We examined HIV-1 RNA concentration, co-receptor usage, and CSF compartmentalization in paired CSF and blood samples from 19 adults not on treatment. Full-length envelope CSF- and plasma-derived reporter viruses were generated from 3 subjects and phenotypically characterized in human primary CD4
Sprache	Englisch
Erscheinungsdatum	2024-05-07
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-024-01207-w
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV: Results from a retrospective cohort study.

Oomen, Patrick G A / Dijkstra, Suzan / Hofstra, L Marije / Nijhuis, Monique M / Verbon, Annelies / Mudrikova, Tania / Wensing, Annemarie M J / Hoepelman, Andy I M / Van Welzen, Berend J

Journal of medical virology

2023 Band 95, Heft 10, Seite(n) e29178

Abstract: The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which ... ...

Abstract	The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010-2020 consisting of two nucleos(-t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50-499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non-adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI- (n = 5119; 20.9%), PI- (n = 8935; 36.4%), and NNRTI-use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non-blip VLs were RNA
Mesh-Begriff(e)	Humans ; Cohort Studies ; Retrospective Studies ; Viremia/etiology ; HIV Infections/drug therapy ; HIV Infections/complications ; Reverse Transcriptase Inhibitors/therapeutic use ; RNA/therapeutic use ; Viral Load ; Anti-HIV Agents/therapeutic use ; Antiretroviral Therapy, Highly Active
Chemische Substanzen	Reverse Transcriptase Inhibitors ; RNA (63231-63-0) ; Anti-HIV Agents
Sprache	Englisch
Erscheinungsdatum	2023-09-22
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29178
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Digital PCR as a tool to measure HIV persistence.

Rutsaert, Sofie / Bosman, Kobus / Trypsteen, Wim / Nijhuis, Monique / Vandekerckhove, Linos

Retrovirology

2018 Band 15, Heft 1, Seite(n) 16

Abstract: Although antiretroviral therapy is able to suppress HIV replication in infected patients, the virus persists and rebounds when treatment is stopped. In order to find a cure that can eradicate the latent reservoir, one must be able to quantify the ... ...

Abstract	Although antiretroviral therapy is able to suppress HIV replication in infected patients, the virus persists and rebounds when treatment is stopped. In order to find a cure that can eradicate the latent reservoir, one must be able to quantify the persisting virus. Traditionally, HIV persistence studies have used real-time PCR (qPCR) to measure the viral reservoir represented by HIV DNA and RNA. Most recently, digital PCR is gaining popularity as a novel approach to nucleic acid quantification as it allows for absolute target quantification. Various commercial digital PCR platforms are nowadays available that implement the principle of digital PCR, of which Bio-Rad's QX200 ddPCR is currently the most used platform in HIV research. Quantification of HIV by digital PCR is proving to be a valuable improvement over qPCR as it is argued to have a higher robustness to mismatches between the primers-probe set and heterogeneous HIV, and forfeits the need for a standard curve, both of which are known to complicate reliable quantification. However, currently available digital PCR platforms occasionally struggle with unexplained false-positive partitions, and reliable segregation between positive and negative droplets remains disputed. Future developments and advancements of the digital PCR technology are promising to aid in the accurate quantification and characterization of the persistent HIV reservoir.
Mesh-Begriff(e)	Antiretroviral Therapy, Highly Active ; DNA, Viral/analysis ; DNA, Viral/genetics ; HIV Infections/virology ; HIV-1/genetics ; Humans ; Polymerase Chain Reaction ; Proviruses/genetics ; RNA, Viral/analysis ; RNA, Viral/genetics ; Sensitivity and Specificity ; Virus Latency
Chemische Substanzen	DNA, Viral ; RNA, Viral
Sprache	Englisch
Erscheinungsdatum	2018-01-30
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/s12977-018-0399-0
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Point-of-Care Detection of Nonadherence to Antiretroviral Treatment for HIV-1 in Resource-Limited Settings Using Drug Level Testing for Efavirenz, Lopinavir, and Dolutegravir: A Validation and Pharmacokinetic Simulation Study.

Hermans, Lucas E / Nijhuis, Monique / Tempelman, Hugo A / Houts, Tom / Schuurman, Rob / Burger, David M / Wensing, Annemarie M J / ter Heine, Rob

Journal of acquired immune deficiency syndromes (1999)

2021 Band 87, Heft 4, Seite(n) 1072–1078

Abstract: Background: Virological failure during antiretroviral treatment (ART) may indicate the presence of drug resistance, but may also originate from nonadherence. Qualitative detection of ART components using drug level testing may be used to differentiate ... ...

Abstract	Background: Virological failure during antiretroviral treatment (ART) may indicate the presence of drug resistance, but may also originate from nonadherence. Qualitative detection of ART components using drug level testing may be used to differentiate between these scenarios. We aimed to validate and implement qualitative point-of-care drug level tests for efavirenz (EFV), lopinavir (LPV), and dolutegravir (DTG) in rural South Africa. Methods: Qualitative performance of immunoassays for EFV, LPV, and DTG was assessed by calculating limit of detection (LoD), region of uncertainty, and qualitative agreement with a reference test. Minimum duration of nonadherence resulting in a negative drug level test was assessed by simulation of treatment cessation using validated population pharmacokinetic models. Results: LoD was 0.05 mg/L for EFV, 0.06 mg/L for LPV, and 0.02 mg/L for DTG. Region of uncertainty was 0.01-0.06 mg/L for EFV, 0.01-0.07 mg/L for LPV, and 0.01-0.02 mg/L for DTG. Qualitative agreement with reference testing at the LoD in patient samples was 95.2% (79/83) for EFV, 99.3% (140/141) for LPV, and 100% (118/118) for DTG. After simulated treatment cessation, median time to undetectability below LoD was 7 days [interquartile range (IQR) 4-13] for EFV, 30 hours (IQR 24-36) for LPV, and 6 days (IQR 4-7) for DTG. Conclusions: We demonstrate that qualitative ART drug level testing using immunoassays is feasible in a rural resource-limited setting. Implementation of this technology enables reliable detection of recent nonadherence and may allow for rapid and cost-effective differentiation between patients in need for adherence counseling and patients who require drug resistance testing or alternative treatment.
Mesh-Begriff(e)	Alkynes/administration & dosage ; Alkynes/pharmacokinetics ; Alkynes/therapeutic use ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/blood ; Benzoxazines/administration & dosage ; Benzoxazines/pharmacokinetics ; Benzoxazines/therapeutic use ; Cyclopropanes/administration & dosage ; Cyclopropanes/pharmacokinetics ; Cyclopropanes/therapeutic use ; HIV Infections/drug therapy ; HIV Infections/metabolism ; HIV-1 ; Heterocyclic Compounds, 3-Ring/administration & dosage ; Heterocyclic Compounds, 3-Ring/pharmacokinetics ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Humans ; Immunoenzyme Techniques/methods ; Limit of Detection ; Lopinavir/administration & dosage ; Lopinavir/pharmacokinetics ; Lopinavir/therapeutic use ; Medication Adherence ; Oxazines/administration & dosage ; Oxazines/pharmacokinetics ; Oxazines/therapeutic use ; Piperazines/administration & dosage ; Piperazines/pharmacokinetics ; Piperazines/therapeutic use ; Point-of-Care Testing/economics ; Point-of-Care Testing/standards ; Pyridones/administration & dosage ; Pyridones/pharmacokinetics ; Pyridones/therapeutic use ; Reproducibility of Results ; Rural Population ; South Africa
Chemische Substanzen	Alkynes ; Anti-HIV Agents ; Benzoxazines ; Cyclopropanes ; Heterocyclic Compounds, 3-Ring ; Oxazines ; Piperazines ; Pyridones ; Lopinavir (2494G1JF75) ; dolutegravir (DKO1W9H7M1) ; efavirenz (JE6H2O27P8)
Sprache	Englisch
Erscheinungsdatum	2021-06-21
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000002681
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen.

Stam, Arjen J / Buchholtz, Ninée V E J / Bierman, Wouter F W / van Crevel, Reinout / Hoepelman, Andy I M / Claassen, Mark A A / Ammerlaan, Heidi S M / van Welzen, Berend J / van Kasteren, Marjo E E / van Lelyveld, Steven F L / de Jong, Dorien / Tesselaar, Kiki / van Luin, Matthijs / Nijhuis, Monique / Wensing, Annemarie M J / Lowerit Study Team

Viruses

2024 Band 16, Heft 2

Abstract: There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in ...

Abstract	There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV.
Mesh-Begriff(e)	Humans ; Darunavir/therapeutic use ; Darunavir/pharmacology ; Viremia ; HIV Infections/drug therapy ; Antiretroviral Therapy, Highly Active ; Sequence Analysis ; Viral Load ; Anti-HIV Agents/pharmacology
Chemische Substanzen	Darunavir (YO603Y8113) ; Anti-HIV Agents
Sprache	Englisch
Erscheinungsdatum	2024-01-25
Erscheinungsland	Switzerland
Dokumenttyp	Observational Study ; Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16020182
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Characterization of HIV-1 Infection in Microglia-Containing Human Cerebral Organoids.

Gumbs, Stephanie B H / Berdenis van Berlekom, Amber / Kübler, Raphael / Schipper, Pauline J / Gharu, Lavina / Boks, Marco P / Ormel, Paul R / Wensing, Annemarie M J / de Witte, Lot D / Nijhuis, Monique

Viruses

2022 Band 14, Heft 4

Abstract: The achievement of an HIV cure is dependent on the eradication or permanent silencing of HIV-latent viral reservoirs, including the understudied central nervous system (CNS) reservoir. This requires a deep understanding of the molecular mechanisms of HIV' ...

Abstract	The achievement of an HIV cure is dependent on the eradication or permanent silencing of HIV-latent viral reservoirs, including the understudied central nervous system (CNS) reservoir. This requires a deep understanding of the molecular mechanisms of HIV's entry into the CNS, latency establishment, persistence, and reversal. Therefore, representative CNS culture models that reflect the intercellular dynamics and pathophysiology of the human brain are urgently needed in order to study the CNS viral reservoir and HIV-induced neuropathogenesis. In this study, we characterized a human cerebral organoid model in which microglia grow intrinsically as a CNS culture model to study HIV infection in the CNS. We demonstrated that both cerebral organoids and isolated organoid-derived microglia (oMG), infected with replication-competent HIVbal reporter viruses, support productive HIV infection via the CCR5 co-receptor. Productive HIV infection was only observed in microglial cells. Fluorescence analysis revealed microglia as the only HIV target cell. Susceptibility to HIV infection was dependent on the co-expression of microglia-specific markers and the CD4 and CCR5 HIV receptors. Altogether, this model will be a valuable tool within the HIV research community to study HIV-CNS interactions, the underlying mechanisms of HIV-associated neurological disorders (HAND), and the efficacy of new therapeutic and curative strategies on the CNS viral reservoir.
Mesh-Begriff(e)	AIDS-Associated Nephropathy/pathology ; HIV Infections ; HIV-1/physiology ; Humans ; Microglia ; Organoids/virology ; Receptors, HIV
Chemische Substanzen	Receptors, HIV
Sprache	Englisch
Erscheinungsdatum	2022-04-16
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14040829
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment.

Hermans, Lucas E / Hofstra, Laura M / Schuurman, Rob / Ter Heine, Rob / Burger, David M / Talboom, Stijn A J / De Jong, Dorien / Tempelman, Hugo A / Venter, Willem D F / Nijhuis, Monique / Wensing, Annemarie M J

AIDS (London, England)

2022 Band 36, Heft 7, Seite(n) 923–931

Abstract: Introduction: Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART ...

Abstract	Introduction: Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART in a subanalysis of a randomized clinical trial comparing different ART monitoring strategies implemented at a rural treatment facility in Limpopo, South Africa. Methods: Participants initiating EFV-based first-line ART (2015-2017) were enrolled and received 96 weeks follow-up. Resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-NRTI's (NNRTIs) was retrospectively assessed by population-based sequencing. Virological failure was defined as a viral load of at least 1000 copies/ml after at least 24 weeks of ART. Results: A total of 207 participants were included, 60.4% (125/207) of whom were female. Median age was 38.8 (interquartile range: 31.4-46.7) years. Median CD4+ cell count was 191 (interquartile range: 70-355) cells/μl. PDR was detected in 12.9% (25/194) of participants with available sequencing results; 19 had NNRTI-resistance, and six had NRTI- and NNRTI-resistance. 26.0% of participants (40/154) with sequencing results and virological follow-up developed virological failure. PDR was independently associated with failure (adjusted hazard ratio: 3.7 [95% confidence interval: 1.68.5], P = 0.002). At failure, 87.5% (7/8) of participants with PDR harboured dual-class resistant virus, versus 16.7% (4/24) of participants without PDR (P = 0.0007). Virological resuppression after failure on first-line ART occurred in 57.7% (15/26) of participants without PDR versus 14.3% (1/7) of participants with PDR (P = 0.09). Conclusion: PDR was detected in 13% of study participants. PDR significantly increased the risk of virological failure of EFV-based ART. Accumulation of resistance at failure and inability to achieve virological resuppression illustrates the profound impact of PDR on treatment outcomes.
Mesh-Begriff(e)	Adult ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Anti-Retroviral Agents/pharmacology ; Anti-Retroviral Agents/therapeutic use ; Drug Resistance ; Drug Resistance, Viral ; Female ; HIV Infections ; HIV Seropositivity/drug therapy ; HIV-1/genetics ; Humans ; Male ; Retrospective Studies ; Viral Load
Chemische Substanzen	Anti-HIV Agents ; Anti-Retroviral Agents
Sprache	Englisch
Erscheinungsdatum	2022-02-01
Erscheinungsland	England
Dokumenttyp	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003182
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Kategorien

Verfügbar in ZB MED Köln/Königswinter

Über subito bestellen

Zusatzmaterialien

Kategorien

Über subito bestellen

Zusatzmaterialien

Kategorien

Über subito bestellen

Zusatzmaterialien

Kategorien

Verfügbar in ZB MED Köln/Königswinter

Über subito bestellen