DOI: 10.5061/dryad.x3ffbg7tv
title: Data from: Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection

description: Using the Olink Explore 1536 platform, we measured 1,463 unique proteins
 in 303 cerebrospinal fluid (CSF) specimens from four clinical centers
 contributed by uninfected controls and 12 groups of people living with
 HIV-1 infection representing the spectrum of progressive untreated and
 treated chronic infection. We present three initial analyses of these
 measurements: an overview of the CSF protein features of the sample;
 correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament
 light chain protein concentrations; and comparison of CSF proteins in
 HIV-associated dementia (HAD) and neurosymptomatic CSF escape (NSE). These
 reveal a complex but coherent picture of CSF protein changes with highest
 concentrations of many proteins during CNS injury in the HAD and NSE
 groups and variable protein changes across the course of systemic HIV-1
 progression that included two common patterns, designated as lymphoid and
 myeloid patterns, related to principal involvement of their underlying
 inflammatory cell lineages. Antiretroviral therapy reduced CSF protein
 perturbations, though not always to control levels. The dataset of these
 CSF protein measurements, along with background clinical information, is
 posted online. Extended studies of this unique dataset will supplement
 this report to provide more detailed characterization of the dynamic
 impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1
 infection, advancing the mechanistic understanding of HIV-1-related CNS
 pathobiology.
description: This was an exploratory study using archived CSF samples from
 four clinical research centers. CSF was collected using standard protocols
 and stored after low speed centrifugation. Samples were selected from
 frozen archives at random to represent defined clinical catogories.
 Proteins were measured using the Olink Explore 1536 platform. The initial
 description of this study is now <em>in press</em> in PLOS
 Pathogens, titled <em>Changes in Cerebrospinal Fluid Proteins across
 the Spectrum of Untreated and Treated Chronic HIV-1
 Infection. </em>This entry includes the full dataset for this study
 and this initial manuscript.
description: # Data from: Changes in cerebrospinal fluid proteins across the spectrum
 of untreated and treated chronic HIV-1 infection
 [https://doi.org/10.5061/dryad.x3ffbg7tv](https://doi.org/10.5061/dryad.x3ffbg7tv) ## Description of the data and file structure This table contains the full dataset related to a study measuring a large number of CSF proteins across a wide range of clinical settings of HIV-1 infection. The study and the general features of the changes in these proteins is described in our manuscript, *Changes in Cerebrospinal Fluid Proteins across the Spectrum of Untreated and Treated Chronic HIV-1 Infection*, that is now in press in *PLOS Pathogens, [https://doi.org/10.1371/journal.ppat.1012470](https://doi.org/10.1371/journal.ppat.1012470)*. This paper introduces the study design, methods and the resultant dataset. It also provides some initial analyses, and emphasizes thaat the dataset is amenable to additional analyses. We invite other investigators to join us in exploiting these data to explore additional issues related to HIV-1 central nervous system (CNS) infection and accompanying inflammation along with neural injury. ### Version log **Oct 2024**: Minor edits were made to the data file and README, including renaming some columns so that each column header has a unique value. ### Files and variables #### File\_1\_Dataset\_of\_CSF\_proteins\_in\_chronic\_HIV\_\_infection\_rev2024-09-10.xlsx **Description:** This table contains the ***full dataset*** related to a study using the ***Olink*** ***Explore 1536*** platform to measure a large number of cerebrospinal fluid (CSF) proteins across a broad spectrum of clinical settings spanning the course of chronic HIV-1 infection, in the absence and presence of antiretroviral therapy (ART). Overall, a total of 1,463 unique proteins were measured, though the concentrations of some of these proteins were, to a variable extent, below the threshold levels of detection (LODs) in the CSF samples.  The study design and the general features of the CSF proteins changes are described in the initial publication indicated by the data table title: *Changes in Cerebrospinal Fluid Proteins across the Spectrum of Untreated and Treated Chronic HIV-1 Infection*. The data are posted here on the Dryad site to assure their availability to other investigators who wish to review these data and, in particular, perform additional analyses of these data (DOI:10.5061/dryad.x3ffbg7tv). We encourage others to join us in using these data to address additional issues related to HIV CNS infection, injury and inflammation, as well as other facets of this infection, as we also engage in our own further analyses. The CSF specimens analyzed in this study represent a collection of convenience samples obtained from people living with HIV (PLWH) that were collected and archived in four centers with programs studying the neurological aspects of HIV-1 infection. The samples are grouped into clinically defined categories. In addition to samples from a group of uninfected, HIV seronegative (HIV-) control individuals, they include samples from 13 groups of PLWH. The latter include: a set of five groups of *untreated* and neurologically asymptomatic individuals defined by systemic disease progression (with five brackets of blood CD4+ T-lymphocyte counts: *&gt;500*, *350 – 499*, *200 – 349*, *50 – 199*, and *&lt;50* cells per µL); an *untreated* group with endogenous viral control (elite controllers, *elites*); *untreated* patients presenting with clinically-diagnosed moderate to severe subacute HIV-associated dementia (*HAD*) with underlying HIV-1 encephalitis; antiviral drug-treated PLWH with viral suppression, without and with elevated CSF neurofilament light chain protein (NfL) concentrations (*RxNFL-* and *RxNFL+*); and *treated* individuals with three types of HIV-1 CSF escape, neurosymptomatic escape (*NSE*), asymptomatic escape (*AsE*) and secondary escape provoked by another CNS infection (*2ryE*); along with a small (N = 4) group of miscellaneous samples from PLWH who do not fit into the other groups and were not included in the initial published group analysis. The smaller left section of the table documents the background demographic and clinical characteristics of the grouped individuals. The participant ages in each group are presented as Mean +/- SD for the group rather than listing individual ages as part of the deidentification process of individual participants. This section includes the clinical laboratory features related to characterization of HIV-1 infection, along with some other useful background laboratory data including CSF and blood neopterin and CSF neurofilament light chain protein (NfL) measured earlier in some of the individuals—the values of CSF NfL are also presented as age-adjusted values calculated as previously described (Yilmaz A, Blennow K, Hagberg L, Nilsson S, Price RW, Schouten J, et al. *Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls.* Expert Rev Mol Diagn. 2017;17(8):761-70. doi: 10.1080/14737159.2017.1341313. PubMed PMID: 28598205). The NfL measurements with pink highlighting are considered to be elevated, and thus abnormal, according to this previous experience (**Columns Y and Z**). The larger right side of the table lists the CSF protein concentration measurements obtained using the ***Olink Explore 1536*** platform ([https://olink.com/about/about-olink](https://olink.com/about/about-olink)) that are reported in NPX log2 values. These proteins are identified by their gene names as listed in the UniProt database ([https://www.uniprot.org/uniprotkb/](https://www.uniprot.org/uniprotkb/)). The following descriptions relate to the ***annotations*** included within this section of the Table: Olink measurements that have been highlighted in light brown throughout this section of the table were reported by Olink with quality control (**QC**)** warnings**. These warnings were ignored in our initial analysis, as discussed in the related ***PLOS Pathogens*** paper now *in press*. The ***Olink Explore 1536***** **included **quadruplicate measurements** of three proteins, CXCL8, IL6 and TNF. In our initial analysis we randomly selected only one of these values for inclusion in exploring the protein features of the samples. In **Row 1 **these four repeats are highlighted in yellow with the sample selected for inclusion in the initial analysis highlighted in darker gold. The four column heads for these three proteins have also been numbered (e.g., CXCL8 (1), CXCL8 (2), CXCL8 (3), etc.) to provide unique column heads for each set of measurements. Some of the proteins measured in CSF samples were below the ***Olink Explore 1536*** stated levels of detection (**LODs**) in the individual assays. The percent of measurements with *values greater than these LODs* are listed In **Row 329** below the listings of the LODs for each of the four plates used in the individual protein measurements; these percentages are color-coded into graduated brackets for easy reference as defined in **Column AA**, **Rows 340 - 346**. ## Code/software Microsoft Excel ## Access information Other publicly accessible locations of the data: * None Data was derived from the following sources: * Measurement of CSF proteins using Olink Explore platform * Clinical background data relevant to HIV infection