Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1
Objectives: The aim of this study was to assess soluble CD30 (sCD30), a protein that colocalises with HIV-1 RNA and DNA in lymphoid cells and tissues, in cerebrospinal fluid (CSF) as a marker of HIV-1 infection in the central nervous system (CNS). Methods: This was a cross-sectional study using arch...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
|
| Series: | Journal of Virus Eradication |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2055664020300066 |
| _version_ | 1818598867033128960 |
|---|---|
| author | Michael J. Peluso Cassandra Thanh Cecilia A. Prator Louise E. Hogan Victor M. Arechiga Sophie Stephenson Philip J. Norris Clara Di Germanio Dietmar Fuchs Henrik Zetterberg Steven G. Deeks Magnus Gisslén Richard W. Price Timothy J. Henrich |
| author_facet | Michael J. Peluso Cassandra Thanh Cecilia A. Prator Louise E. Hogan Victor M. Arechiga Sophie Stephenson Philip J. Norris Clara Di Germanio Dietmar Fuchs Henrik Zetterberg Steven G. Deeks Magnus Gisslén Richard W. Price Timothy J. Henrich |
| author_sort | Michael J. Peluso |
| collection | DOAJ |
| description | Objectives: The aim of this study was to assess soluble CD30 (sCD30), a protein that colocalises with HIV-1 RNA and DNA in lymphoid cells and tissues, in cerebrospinal fluid (CSF) as a marker of HIV-1 infection in the central nervous system (CNS). Methods: This was a cross-sectional study using archived samples from two clinical cohorts. Soluble CD30 concentrations were measured in paired CSF and plasma from untreated viraemic individuals (n=52), individuals on suppressive antiretroviral therapy (ART) (n=33), HIV-1 controllers (n=10), participants with CSF HIV-1 ‘escape’ (n=11) and controls without HIV-1 infection (n=16). Nonparametric tests were used to compare levels across groups and evaluate correlations with HIV-1 RNA, CSF neurofilament light chain protein (NFL) and neopterin. Results: Compared with controls (median 30 ng/mL, interquartile range [IRQ] 23–50), plasma sCD30 levels were elevated in viraemic participants (75 ng/mL, 52–116; P<0.001), but not in those on suppressive ART (38 ng/mL, 32–62). In contrast, CSF sCD30 levels were elevated in ART-suppressed individuals (34 ng/mL, 19–46; P=0.001) and in those with CSF ‘escape’ (33 ng/mL, 27–40; P=0.004) compared with controls (18 ng/mL, 11–23), but not in untreated viraemic individuals. No association was observed between CSF sCD30 and plasma HIV-1 RNA, concurrent or nadir CD4+ T cell count, duration of infection or plasma sCD30. CSF sCD30 correlated with CSF NFL (r=0.34, P=0.001). Conclusions: In contrast to plasma, sCD30 levels are elevated in the CSF of individuals with HIV-1 infection who are on suppressive ART. Elevated levels of sCD30 in the CSF may be an indicator of persistent CNS HIV-1 infection, although the mechanism underlying this elevation warrants further investigation. |
| first_indexed | 2024-12-16T12:10:31Z |
| format | Article |
| id | doaj.art-e72fe490946d41de944dc6da75154a4b |
| institution | Directory Open Access Journal |
| issn | 2055-6640 |
| language | English |
| last_indexed | 2024-12-16T12:10:31Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Virus Eradication |
| spelling | doaj.art-e72fe490946d41de944dc6da75154a4b2022-12-21T22:32:13ZengElsevierJournal of Virus Eradication2055-66402020-01-01611926Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1Michael J. Peluso0Cassandra Thanh1Cecilia A. Prator2Louise E. Hogan3Victor M. Arechiga4Sophie Stephenson5Philip J. Norris6Clara Di Germanio7Dietmar Fuchs8Henrik Zetterberg9Steven G. Deeks10Magnus Gisslén11Richard W. Price12Timothy J. Henrich13Division of HIV, Infectious Diseases, and Global Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, USA; Corresponding author: Michael Peluso, MD 1001 Potrero Ave. Building 3, San Francisco, CA 94110Division of Experimental Medicine, University of California San Francisco, San Francisco, USADivision of Experimental Medicine, University of California San Francisco, San Francisco, USADivision of Experimental Medicine, University of California San Francisco, San Francisco, USADepartment of Neurology, University of California San Francisco, San Francisco, USADepartment of Neurology, University of California San Francisco, San Francisco, USAVitalant Research Institute, San Francisco, USAVitalant Research Institute, San Francisco, USADivision of Biological Chemistry, Innsbruck Medical University, Innsbruck, AustriaDepartment of Psychiatry and Neurochemistry, Institute for Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenDivision of HIV, Infectious Diseases, and Global Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, USADepartment of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, SwedenDepartment of Neurology, University of California San Francisco, San Francisco, USADivision of Experimental Medicine, University of California San Francisco, San Francisco, USAObjectives: The aim of this study was to assess soluble CD30 (sCD30), a protein that colocalises with HIV-1 RNA and DNA in lymphoid cells and tissues, in cerebrospinal fluid (CSF) as a marker of HIV-1 infection in the central nervous system (CNS). Methods: This was a cross-sectional study using archived samples from two clinical cohorts. Soluble CD30 concentrations were measured in paired CSF and plasma from untreated viraemic individuals (n=52), individuals on suppressive antiretroviral therapy (ART) (n=33), HIV-1 controllers (n=10), participants with CSF HIV-1 ‘escape’ (n=11) and controls without HIV-1 infection (n=16). Nonparametric tests were used to compare levels across groups and evaluate correlations with HIV-1 RNA, CSF neurofilament light chain protein (NFL) and neopterin. Results: Compared with controls (median 30 ng/mL, interquartile range [IRQ] 23–50), plasma sCD30 levels were elevated in viraemic participants (75 ng/mL, 52–116; P<0.001), but not in those on suppressive ART (38 ng/mL, 32–62). In contrast, CSF sCD30 levels were elevated in ART-suppressed individuals (34 ng/mL, 19–46; P=0.001) and in those with CSF ‘escape’ (33 ng/mL, 27–40; P=0.004) compared with controls (18 ng/mL, 11–23), but not in untreated viraemic individuals. No association was observed between CSF sCD30 and plasma HIV-1 RNA, concurrent or nadir CD4+ T cell count, duration of infection or plasma sCD30. CSF sCD30 correlated with CSF NFL (r=0.34, P=0.001). Conclusions: In contrast to plasma, sCD30 levels are elevated in the CSF of individuals with HIV-1 infection who are on suppressive ART. Elevated levels of sCD30 in the CSF may be an indicator of persistent CNS HIV-1 infection, although the mechanism underlying this elevation warrants further investigation.http://www.sciencedirect.com/science/article/pii/S2055664020300066HIV-1reservoircentral nervous system (CNS)cerebrospinal fluid (CSF)CD30 |
| spellingShingle | Michael J. Peluso Cassandra Thanh Cecilia A. Prator Louise E. Hogan Victor M. Arechiga Sophie Stephenson Philip J. Norris Clara Di Germanio Dietmar Fuchs Henrik Zetterberg Steven G. Deeks Magnus Gisslén Richard W. Price Timothy J. Henrich Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1 Journal of Virus Eradication HIV-1 reservoir central nervous system (CNS) cerebrospinal fluid (CSF) CD30 |
| title | Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1 |
| title_full | Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1 |
| title_fullStr | Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1 |
| title_full_unstemmed | Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1 |
| title_short | Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1 |
| title_sort | cerebrospinal fluid soluble cd30 elevation despite suppressive antiretroviral therapy in individuals living with hiv 1 |
| topic | HIV-1 reservoir central nervous system (CNS) cerebrospinal fluid (CSF) CD30 |
| url | http://www.sciencedirect.com/science/article/pii/S2055664020300066 |
| work_keys_str_mv | AT michaeljpeluso cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT cassandrathanh cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT ceciliaaprator cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT louiseehogan cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT victormarechiga cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT sophiestephenson cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT philipjnorris cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT claradigermanio cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT dietmarfuchs cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT henrikzetterberg cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT stevengdeeks cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT magnusgisslen cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT richardwprice cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 AT timothyjhenrich cerebrospinalfluidsolublecd30elevationdespitesuppressiveantiretroviraltherapyinindividualslivingwithhiv1 |