Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study
Abstract Objectives Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiv...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2021-02, Vol.76 (3), p.743-752 |
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| creator | Force, Gilles Ghout, Idir Ropers, Jacques Carcelain, Guislaine Marigot-Outtandy, Dhiba Hahn, Valérie Darchy, Natacha Defferriere, Hélène Bouaziz-Amar, Elodie Carlier, Robert Dorgham, Karim Callebert, Jacques Peytavin, Gilles Delaugerre, Constance de Truchis, Pierre |
| description | Abstract
Objectives
Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9.
Methods
Thirty-one patients, aged 18–65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96.
Results
The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4–7) at baseline to 10 (9–11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8–2.2) to 1.0 (0.6–2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P |
| doi_str_mv | 10.1093/jac/dkaa473 |
| format | Article |
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Objectives
Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9.
Methods
Thirty-one patients, aged 18–65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96.
Results
The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4–7) at baseline to 10 (9–11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8–2.2) to 1.0 (0.6–2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P < 0.001) and plasma CXCL10 decrease at W96 (P = 0.001).
Conclusions
In patients with HAND, a significant cognitive improvement was observed after the ARV intensification strategy, with a higher CPE score. Cognitive improvement was more often observed in the case of a switch of two drug classes, arguing for better control of CNS HIV immune activation.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkaa473</identifier><identifier>PMID: 33179033</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><ispartof>Journal of antimicrobial chemotherapy, 2021-02, Vol.76 (3), p.743-752</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c320t-f147abc077c0cafc29ecdba33bbd6b0620d7b0813f4f3b394c72677531d90ae83</citedby><cites>FETCH-LOGICAL-c320t-f147abc077c0cafc29ecdba33bbd6b0620d7b0813f4f3b394c72677531d90ae83</cites><orcidid>0000-0002-4359-537X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33179033$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Force, Gilles</creatorcontrib><creatorcontrib>Ghout, Idir</creatorcontrib><creatorcontrib>Ropers, Jacques</creatorcontrib><creatorcontrib>Carcelain, Guislaine</creatorcontrib><creatorcontrib>Marigot-Outtandy, Dhiba</creatorcontrib><creatorcontrib>Hahn, Valérie</creatorcontrib><creatorcontrib>Darchy, Natacha</creatorcontrib><creatorcontrib>Defferriere, Hélène</creatorcontrib><creatorcontrib>Bouaziz-Amar, Elodie</creatorcontrib><creatorcontrib>Carlier, Robert</creatorcontrib><creatorcontrib>Dorgham, Karim</creatorcontrib><creatorcontrib>Callebert, Jacques</creatorcontrib><creatorcontrib>Peytavin, Gilles</creatorcontrib><creatorcontrib>Delaugerre, Constance</creatorcontrib><creatorcontrib>de Truchis, Pierre</creatorcontrib><creatorcontrib>NEURO+3 STUDY GROUP</creatorcontrib><title>Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract
Objectives
Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9.
Methods
Thirty-one patients, aged 18–65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96.
Results
The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4–7) at baseline to 10 (9–11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8–2.2) to 1.0 (0.6–2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P < 0.001) and plasma CXCL10 decrease at W96 (P = 0.001).
Conclusions
In patients with HAND, a significant cognitive improvement was observed after the ARV intensification strategy, with a higher CPE score. Cognitive improvement was more often observed in the case of a switch of two drug classes, arguing for better control of CNS HIV immune activation.</description><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kDFv2zAQRomiReO6nboHnIoCgZKjThatbIWRNAaCdmm7CifymDCxRIekDPjfV4bdjpluuIcHfE-IzwouFTR49UTmyj4TVRrfiJmqaihKaNRbMQOERaGrBZ6JDyk9AUC9qJfvxRmi0g0gzsRu3W9j2HHPQ5bBybv1n4JSCsZTZisHHmMw4WHw2e9YWp9CtByTJJc5Shqyj5wngY-0kfmRI2330g-Zh-SdN5R9GK4PD_njoLpAmfJo9x_FO0ebxJ9Ody5-3978Wt0V9z-_r1ff7guDJeTCqUpTZ0BrA4acKRs2tiPErrN1B3UJVnewVOgqhx02ldFlrfUClW2AeIlz8fXonUa-jJxy2_tkeLOhgcOY2nKqBcuqnFrMxcURNTGkFNm12-h7ivtWQXsI3U6h21PoiT4_iceuZ_uf_Vd2Ar4cgTBuXzX9BX1Sihc</recordid><startdate>20210211</startdate><enddate>20210211</enddate><creator>Force, Gilles</creator><creator>Ghout, Idir</creator><creator>Ropers, Jacques</creator><creator>Carcelain, Guislaine</creator><creator>Marigot-Outtandy, Dhiba</creator><creator>Hahn, Valérie</creator><creator>Darchy, Natacha</creator><creator>Defferriere, Hélène</creator><creator>Bouaziz-Amar, Elodie</creator><creator>Carlier, Robert</creator><creator>Dorgham, Karim</creator><creator>Callebert, Jacques</creator><creator>Peytavin, Gilles</creator><creator>Delaugerre, Constance</creator><creator>de Truchis, Pierre</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4359-537X</orcidid></search><sort><creationdate>20210211</creationdate><title>Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study</title><author>Force, Gilles ; Ghout, Idir ; Ropers, Jacques ; Carcelain, Guislaine ; Marigot-Outtandy, Dhiba ; Hahn, Valérie ; Darchy, Natacha ; Defferriere, Hélène ; Bouaziz-Amar, Elodie ; Carlier, Robert ; Dorgham, Karim ; Callebert, Jacques ; Peytavin, Gilles ; Delaugerre, Constance ; de Truchis, Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c320t-f147abc077c0cafc29ecdba33bbd6b0620d7b0813f4f3b394c72677531d90ae83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Force, Gilles</creatorcontrib><creatorcontrib>Ghout, Idir</creatorcontrib><creatorcontrib>Ropers, Jacques</creatorcontrib><creatorcontrib>Carcelain, Guislaine</creatorcontrib><creatorcontrib>Marigot-Outtandy, Dhiba</creatorcontrib><creatorcontrib>Hahn, Valérie</creatorcontrib><creatorcontrib>Darchy, Natacha</creatorcontrib><creatorcontrib>Defferriere, Hélène</creatorcontrib><creatorcontrib>Bouaziz-Amar, Elodie</creatorcontrib><creatorcontrib>Carlier, Robert</creatorcontrib><creatorcontrib>Dorgham, Karim</creatorcontrib><creatorcontrib>Callebert, Jacques</creatorcontrib><creatorcontrib>Peytavin, Gilles</creatorcontrib><creatorcontrib>Delaugerre, Constance</creatorcontrib><creatorcontrib>de Truchis, Pierre</creatorcontrib><creatorcontrib>NEURO+3 STUDY GROUP</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Force, Gilles</au><au>Ghout, Idir</au><au>Ropers, Jacques</au><au>Carcelain, Guislaine</au><au>Marigot-Outtandy, Dhiba</au><au>Hahn, Valérie</au><au>Darchy, Natacha</au><au>Defferriere, Hélène</au><au>Bouaziz-Amar, Elodie</au><au>Carlier, Robert</au><au>Dorgham, Karim</au><au>Callebert, Jacques</au><au>Peytavin, Gilles</au><au>Delaugerre, Constance</au><au>de Truchis, Pierre</au><aucorp>NEURO+3 STUDY GROUP</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2021-02-11</date><risdate>2021</risdate><volume>76</volume><issue>3</issue><spage>743</spage><epage>752</epage><pages>743-752</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract
Objectives
Despite the effectiveness of antiretroviral (ARV) therapy to control HIV infection, HIV-associated neurocognitive disorders (HAND) remain frequent. The Neuro+3 study assessed the cognitive improvement associated with ARV intensification based on increased CNS penetration effectiveness (CPE) scoring ≥+3 and total CPE score ≥9.
Methods
Thirty-one patients, aged 18–65 years, with confirmed diagnosis of HAND and effective ARV therapy were included. The cognitive improvement was measured using Frascati three-stage classification and global deficit score (GDS) after 48 and 96 weeks of ARV intensification. Ultrasensitive HIV-RNA, neopterin, soluble CD14, CCL2, CXCL10, IL6, IL8 and NF-L were measured in plasma and cerebrospinal fluid at Day 0 (baseline), Week 48 (W48) and W96.
Results
The intensified ARV was associated with a median (IQR) CPE score increase from 6 (4–7) at baseline to 10 (9–11). From baseline to W96, the median (IQR) GDS decreased from 1.4 (0.8–2.2) to 1.0 (0.6–2.0) (P = 0.009); HAND classification improved from 2 to 1 HIV-associated dementia, 22 to 8 mild neurocognitive disorders, 7 to 17 asymptomatic neurocognitive impairment and 0 to 5 patients without any neurocognitive alterations (P = 0.001). In multivariable linear regression analysis, GDS improvement at W96 was significantly associated with CPE score ≥9 after intensification (P = 0.014), CD4 lymphocyte increase at W48 (P < 0.001) and plasma CXCL10 decrease at W96 (P = 0.001).
Conclusions
In patients with HAND, a significant cognitive improvement was observed after the ARV intensification strategy, with a higher CPE score. Cognitive improvement was more often observed in the case of a switch of two drug classes, arguing for better control of CNS HIV immune activation.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33179033</pmid><doi>10.1093/jac/dkaa473</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4359-537X</orcidid></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| title | Improvement of HIV-associated neurocognitive disorders after antiretroviral therapy intensification: the Neuro+3 study |
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