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Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.

Abstract Acute human immunodeficiency virus (HIV) infection is associated with a marked induction of several pathways that are linked to inflammation and CD4 T-cell depletion. Many of these processes do not fully resolve on short-term combination antiretroviral therapy (cART) (<5 years), despite complete and durable suppression of viremia. The effects of long-term (>15 years) successful antiretroviral therapy (ART) and the linkage between levels of biomarkers remain unclear. Therefore, the present study aims to assess the host plasma proteome in a well-defined clinical material from HIV-1-positive male patients on successful long-term ART (>15 years) and compared them with age-matched healthy controls and treatment-naïve male patients with viremia in a cross-sectional manner.Plasma samples were obtained from 3 categories of age-matched HIV-1-positive male patients on long-term successfully (ART, n = 10) with a median (Interquartile range, IQR) of 19 (17-20) years, treatment-naïve patients with viremia (VP, n = 14), and HIV-1-negative persons (HC, n = 11). Plasma proteome was analyzed using the proximity extension assay targeting 92 factors. Statistical analyses were performed with GraphPad Prism v7, R-packages, and Qlucore Omics Explorer v3.2. Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG), and interactions of specific molecules were identified using Path Designer integrated into Ingenuity Pathway Analysis (IPA).Group wise comparison identified 53 soluble factors, which differed between the groups (P < .05). Cluster analysis identified 13 discrete soluble factors (CD8A, CRTAM, CXCL13, EGF, CD5, CD40, CXCL9, Gal-1, IL12RB1, KLRD1, PD-1, CASP-8 and TNFRSF9) between the studied groups (adjusted P < .001). The long-term successfully ART-treated individuals clustered and networked with the HC while VPs clustered separately. All of the proinflammatory cytokines and chemokines were normalized back to levels of healthy controls in long-term successfully ART-treated individuals, but not the levels of KLRD1 and PGDFB.sKLRD1 that is involved in the regulation of natural killer cell (NK) mediated cytotoxicity, failed to be restored to the level of HIV-negative individuals despite successful long-term ART. Additional analysis of NK cells along with T-cell subsets can provide insights into the long-term effects of ART on the immune system.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title medicine
Publication Year Start




PMID- 29384862
OWN - NLM
STAT- MEDLINE
DCOM- 20180209
LR  - 20180209
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Linking)
VI  - 97
IP  - 5
DP  - 2018 Feb
TI  - Plasma soluble factor following two decades prolonged suppressive antiretroviral 
      therapy in HIV-1-positive males: A cross-sectional study.
PG  - e9759
LID - 10.1097/MD.0000000000009759 [doi]
AB  - Acute human immunodeficiency virus (HIV) infection is associated with a marked
      induction of several pathways that are linked to inflammation and CD4 T-cell
      depletion. Many of these processes do not fully resolve on short-term combination
      antiretroviral therapy (cART) (&lt;5 years), despite complete and durable
      suppression of viremia. The effects of long-term (&gt;15 years) successful
      antiretroviral therapy (ART) and the linkage between levels of biomarkers remain 
      unclear. Therefore, the present study aims to assess the host plasma proteome in 
      a well-defined clinical material from HIV-1-positive male patients on successful 
      long-term ART (&gt;15 years) and compared them with age-matched healthy controls and
      treatment-naive male patients with viremia in a cross-sectional manner.Plasma
      samples were obtained from 3 categories of age-matched HIV-1-positive male
      patients on long-term successfully (ART, n = 10) with a median (Interquartile
      range, IQR) of 19 (17-20) years, treatment-naive patients with viremia (VP, n =
      14), and HIV-1-negative persons (HC, n = 11). Plasma proteome was analyzed using 
      the proximity extension assay targeting 92 factors. Statistical analyses were
      performed with GraphPad Prism v7, R-packages, and Qlucore Omics Explorer v3.2.
      Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and
      Genomes (KEGG), and interactions of specific molecules were identified using Path
      Designer integrated into Ingenuity Pathway Analysis (IPA).Group wise comparison
      identified 53 soluble factors, which differed between the groups (P &lt; .05).
      Cluster analysis identified 13 discrete soluble factors (CD8A, CRTAM, CXCL13,
      EGF, CD5, CD40, CXCL9, Gal-1, IL12RB1, KLRD1, PD-1, CASP-8 and TNFRSF9) between
      the studied groups (adjusted P &lt; .001). The long-term successfully ART-treated
      individuals clustered and networked with the HC while VPs clustered separately.
      All of the proinflammatory cytokines and chemokines were normalized back to
      levels of healthy controls in long-term successfully ART-treated individuals, but
      not the levels of KLRD1 and PGDFB.sKLRD1 that is involved in the regulation of
      natural killer cell (NK) mediated cytotoxicity, failed to be restored to the
      level of HIV-negative individuals despite successful long-term ART. Additional
      analysis of NK cells along with T-cell subsets can provide insights into the
      long-term effects of ART on the immune system.
FAU - Sperk, Maike
AU  - Sperk M
AD  - Divison of Clinical Microbiology, Department of Laboratory Medicine, Karolinska
      Institutet, Huddinge.
FAU - Zhang, Wang
AU  - Zhang W
AD  - Divison of Clinical Microbiology, Department of Laboratory Medicine, Karolinska
      Institutet, Huddinge.
AD  - Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH
      Royal Institute of Technology, Solna.
FAU - Nowak, Piotr
AU  - Nowak P
AD  - Department of Medicine Huddinge, Unit of Infectious Diseases, Karolinska
      Institutet, Karolinska University Hospital, Stockholm, Sweden.
FAU - Neogi, Ujjwal
AU  - Neogi U
AD  - Divison of Clinical Microbiology, Department of Laboratory Medicine, Karolinska
      Institutet, Huddinge.
AD  - Science for Life Laboratory, Division of Proteomics and Nanobiotechnology, KTH
      Royal Institute of Technology, Solna.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Blood Proteins)
RN  - 0 (Cytokines)
SB  - AIM
SB  - IM
MH  - Anti-HIV Agents/*therapeutic use
MH  - Antiretroviral Therapy, Highly Active
MH  - Biomarkers/blood
MH  - Blood Proteins/*metabolism
MH  - Case-Control Studies
MH  - Cross-Sectional Studies
MH  - Cytokines/*blood
MH  - Drug Administration Schedule
MH  - HIV Infections/*blood/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
EDAT- 2018/02/01 06:00
MHDA- 2018/02/10 06:00
CRDT- 2018/02/01 06:00
PHST- 2018/02/01 06:00 [entrez]
PHST- 2018/02/01 06:00 [pubmed]
PHST- 2018/02/10 06:00 [medline]
AID - 10.1097/MD.0000000000009759 [doi]
AID - 00005792-201802020-00024 [pii]
PST - ppublish
SO  - Medicine (Baltimore). 2018 Feb;97(5):e9759. doi: 10.1097/MD.0000000000009759.