Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients

Francesca Ferretti, Alba Bigoloni, Laura Passeri, Laura Galli, Valeria Longo, Simonetta Gerevini, Vincenzo Spagnuolo, Magnus Gisslen, Henrik Zetterberg, Dietmar Fuchs, Dario Cattaneo, Giada Caramatti, Adriano Lazzarin, Paola Cinque, Antonella Castagna

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. Methods: This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA <50 copies/mL after at least 96 study weeks were eligible. We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. Results: HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. Conclusions: CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

Original languageEnglish
Article numbere4144
JournalMedicine (United States)
Volume95
Issue number28
DOIs
Publication statusPublished - Jul 1 2016

Fingerprint

Ritonavir
Cerebrospinal Fluid
Biomarkers
HIV
RNA
Kynurenine
Neopterin
Intermediate Filaments
Atazanavir Sulfate
Protease Inhibitors
Nucleosides
Immunoassay
Tryptophan
Liquid Chromatography
Interleukin-6
Mass Spectrometry
Enzyme-Linked Immunosorbent Assay

Keywords

  • atazanavir
  • biomarkers
  • cerebrospinal fluid
  • CSF escape
  • monotherapy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients. / Ferretti, Francesca; Bigoloni, Alba; Passeri, Laura; Galli, Laura; Longo, Valeria; Gerevini, Simonetta; Spagnuolo, Vincenzo; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Cattaneo, Dario; Caramatti, Giada; Lazzarin, Adriano; Cinque, Paola; Castagna, Antonella.

In: Medicine (United States), Vol. 95, No. 28, e4144, 01.07.2016.

Research output: Contribution to journalArticle

Ferretti, Francesca ; Bigoloni, Alba ; Passeri, Laura ; Galli, Laura ; Longo, Valeria ; Gerevini, Simonetta ; Spagnuolo, Vincenzo ; Gisslen, Magnus ; Zetterberg, Henrik ; Fuchs, Dietmar ; Cattaneo, Dario ; Caramatti, Giada ; Lazzarin, Adriano ; Cinque, Paola ; Castagna, Antonella. / Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients. In: Medicine (United States). 2016 ; Vol. 95, No. 28.
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T1 - Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients

AU - Ferretti, Francesca

AU - Bigoloni, Alba

AU - Passeri, Laura

AU - Galli, Laura

AU - Longo, Valeria

AU - Gerevini, Simonetta

AU - Spagnuolo, Vincenzo

AU - Gisslen, Magnus

AU - Zetterberg, Henrik

AU - Fuchs, Dietmar

AU - Cattaneo, Dario

AU - Caramatti, Giada

AU - Lazzarin, Adriano

AU - Cinque, Paola

AU - Castagna, Antonella

PY - 2016/7/1

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N2 - Background: Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. Methods: This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA <50 copies/mL after at least 96 study weeks were eligible. We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. Results: HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. Conclusions: CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

AB - Background: Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. Methods: This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA <50 copies/mL after at least 96 study weeks were eligible. We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. Results: HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. Conclusions: CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

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