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Abstract	Background: Little is known about HIV-1 integrase inhibitor resistance in the CNS. Objectives: This study aimed to evaluate integrase inhibitor resistance in CSF, as a marker of the CNS, and compare it with the resistance in plasma. Methods: HIV integrase was sequenced both in plasma and CSF for 59 HIV-1 patients. The clinical and biological data were collected from clinical routine care. Results: Among the 59 HIV-1 patients, 32 (54.2%) were under antiretroviral (ARV) treatment. The median (IQR) HIV-1 RNA in the plasma of viraemic patients was 5.32 (3.85-5.80) and 3.59 (2.16-4.50) log10 copies/mL versus 4.79 (3.56-5.25) and 3.80 (2.68-4.33) log10 copies/mL in the CSF of ARV-naive and ARV-treated patients, respectively. The patients were mainly infected with non-B subtypes (72.2%) with the most prevalent recombinant form being CRF02_AG (42.4%). The HIV-1 integrase sequences from CSF presented resistance mutations for 9/27 (33.3%) and 8/32 (25.0%) for ARV-naive (L74I, n = 3; L74I/M, n = 1; T97A, n = 1; E157Q, n = 4) and ARV-treated (L74I, n = 6; L74M, n = 1; T97A, n = 1; N155H, n = 1) patients, respectively. Integrase inhibitor resistance mutations in CSF were similar to those in plasma, except for 1/59 patients. Conclusions: This work shows similar integrase inhibitor resistance profiles in the CNS and plasma in a population of HIV-1 viraemic patients.
Language	English
Publishing date	2021-03-10
Publishing country	England
Document type	Journal Article
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkab064
Database	MEDical Literature Analysis and Retrieval System OnLINE

Abstract

Background: Little is known about HIV-1 integrase inhibitor resistance in the CNS.
Objectives: This study aimed to evaluate integrase inhibitor resistance in CSF, as a marker of the CNS, and compare it with the resistance in plasma.
Methods: HIV integrase was sequenced both in plasma and CSF for 59 HIV-1 patients. The clinical and biological data were collected from clinical routine care.
Results: Among the 59 HIV-1 patients, 32 (54.2%) were under antiretroviral (ARV) treatment. The median (IQR) HIV-1 RNA in the plasma of viraemic patients was 5.32 (3.85-5.80) and 3.59 (2.16-4.50) log10 copies/mL versus 4.79 (3.56-5.25) and 3.80 (2.68-4.33) log10 copies/mL in the CSF of ARV-naive and ARV-treated patients, respectively. The patients were mainly infected with non-B subtypes (72.2%) with the most prevalent recombinant form being CRF02_AG (42.4%). The HIV-1 integrase sequences from CSF presented resistance mutations for 9/27 (33.3%) and 8/32 (25.0%) for ARV-naive (L74I, n = 3; L74I/M, n = 1; T97A, n = 1; E157Q, n = 4) and ARV-treated (L74I, n = 6; L74M, n = 1; T97A, n = 1; N155H, n = 1) patients, respectively. Integrase inhibitor resistance mutations in CSF were similar to those in plasma, except for 1/59 patients.
Conclusions: This work shows similar integrase inhibitor resistance profiles in the CNS and plasma in a population of HIV-1 viraemic patients.

Language

English

Publishing date

2021-03-10

Publishing country

England

Document type

Journal Article

ZDB-ID

191709-2

ISSN

1460-2091 ; 0305-7453

ISSN (online)

1460-2091

ISSN

0305-7453

DOI

10.1093/jac/dkab064

Database

MEDical Literature Analysis and Retrieval System OnLINE

Article ; Online: Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

Dragon-Durey, Marie-Agnès / Chen, Xiaoyi / Kirilovsky, Amos / Ben Hamouda, Nadine / El Sissy, Carine / Russick, Jules / Charpentier, Etienne / Binois, Yannick / Marliot, Florence / Meylan, Maxime / Granier, Clémence / Pere, Hélène / Saldmann, Antonin / Rance, Bastien / Jannot, Anne Sophie / Baron, Stéphanie / Chebbi, Mouna / Fayol, Antoine / Josseaume, Nathalie /

Rives-Lange, Claire / Tharaux, Pierre-Louis / Cholley, Bernard / Diehl, Jean-Luc / Arlet, Jean-Benoît / Azizi, Michel / Karras, Alexandre / Czernichow, Sébastien / Smadja, David M / Hulot, Jean-Sébastien / Cremer, Isabelle / Tartour, Eric / Mousseaux, Elie / Pagès, Franck

PloS one

2021 Volume 16, Issue 5, Page(s) e0252026

Abstract: To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital ... ...

Abstract	To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.
MeSH term(s)	Aged ; Biomarkers/metabolism ; Body Mass Index ; COVID-19/complications ; COVID-19/pathology ; COVID-19/virology ; Chemokines/blood ; Chemokines/metabolism ; Cytokines/blood ; Cytokines/metabolism ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Female ; Hospitalization/statistics & numerical data ; Humans ; Intensive Care Units ; Liver/diagnostic imaging ; Liver/physiopathology ; Lung/diagnostic imaging ; Lung/physiopathology ; Male ; Middle Aged ; Obesity/complications ; Obesity/pathology ; Prospective Studies ; RNA, Viral/blood ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification ; Severity of Illness Index
Chemical Substances	Biomarkers ; Chemokines ; Cytokines ; RNA, Viral
Language	English
Publishing date	2021-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0252026
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: No difference in HIV-1 integrase inhibitor resistance between CSF and blood compartments.

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Article ; Online: Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

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