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Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption

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Abstract
Background: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health. Objectives: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated. Methods: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation. Results: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption. Conclusions: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.
Keywords
Pharmacology (medical), Pharmacology, Infectious Diseases, RESTRICTION FACTOR EXPRESSION, INFECTION

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MLA
De Scheerder, Marie-Angélique, et al. “Evaluating Predictive Markers for Viral Rebound and Safety Assessment in Blood and Lumbar Fluid during HIV-1 Treatment Interruption.” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 75, no. 5, 2020, pp. 1311–20, doi:10.1093/jac/dkaa003.
APA
De Scheerder, M.-A., Van Hecke, C., Zetterberg, H., Fuchs, D., De Langhe, N., Rutsaert, S., … Vandekerckhove, L. (2020). Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 75(5), 1311–1320. https://doi.org/10.1093/jac/dkaa003
Chicago author-date
De Scheerder, Marie-Angélique, Clarissa Van Hecke, Henrik Zetterberg, Dietmar Fuchs, Nele De Langhe, Sofie Rutsaert, Bram Vrancken, et al. 2020. “Evaluating Predictive Markers for Viral Rebound and Safety Assessment in Blood and Lumbar Fluid during HIV-1 Treatment Interruption.” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 75 (5): 1311–20. https://doi.org/10.1093/jac/dkaa003.
Chicago author-date (all authors)
De Scheerder, Marie-Angélique, Clarissa Van Hecke, Henrik Zetterberg, Dietmar Fuchs, Nele De Langhe, Sofie Rutsaert, Bram Vrancken, Wim Trypsteen, Ytse Noppe, Beatrijs Van Der Gucht, Jolanda Pelgrom, Filip Van Wanzeele, Sarah Palmer, Philippe Lemey, Magnus Gisslén, and Linos Vandekerckhove. 2020. “Evaluating Predictive Markers for Viral Rebound and Safety Assessment in Blood and Lumbar Fluid during HIV-1 Treatment Interruption.” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 75 (5): 1311–1320. doi:10.1093/jac/dkaa003.
Vancouver
1.
De Scheerder M-A, Van Hecke C, Zetterberg H, Fuchs D, De Langhe N, Rutsaert S, et al. Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. 2020;75(5):1311–20.
IEEE
[1]
M.-A. De Scheerder et al., “Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption,” JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 75, no. 5, pp. 1311–1320, 2020.
@article{8648784,
  abstract     = {Background: Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health.
Objectives: ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated.
Methods: PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation.
Results: Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption.
Conclusions: ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.},
  author       = {De Scheerder, Marie-Angélique and Van Hecke, Clarissa and Zetterberg, Henrik and Fuchs, Dietmar and De Langhe, Nele and Rutsaert, Sofie and Vrancken, Bram and Trypsteen, Wim and Noppe, Ytse and Van Der Gucht, Beatrijs and Pelgrom, Jolanda and Van Wanzeele, Filip and Palmer, Sarah and Lemey, Philippe and Gisslén, Magnus and Vandekerckhove, Linos},
  issn         = {0305-7453},
  journal      = {JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY},
  keywords     = {Pharmacology (medical),Pharmacology,Infectious Diseases,RESTRICTION FACTOR EXPRESSION,INFECTION},
  language     = {eng},
  number       = {5},
  pages        = {1311--1320},
  title        = {Evaluating predictive markers for viral rebound and safety assessment in blood and lumbar fluid during HIV-1 treatment interruption},
  url          = {http://dx.doi.org/10.1093/jac/dkaa003},
  volume       = {75},
  year         = {2020},
}

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