title: High MIP-1β Levels in Plasma Predict Long-Term Immunological Nonresponse to Suppressive Antiretroviral Therapy in HIV Infection.
abstract: BACKGROUND
  HIV-infected patients who fail to reconstitute their CD4 T-cell counts during suppressive antiretroviral therapy (ART) have increased risk of both AIDS-related and non-AIDS-related morbidity and mortality. Improved understanding of immunological nonresponse (INR) is necessary to enable earlier clinical intervention.
  
  
  METHODS
  In a cohort of 112 HIV-infected patients starting ART, we performed a serial analysis of 32 plasma-soluble markers, assessed by multiplex cytokine and enzyme immunoassay. Samples were drawn pre-ART and during the first 3 years of treatment, with a final observation time of 8.4 years (interquartile range, 7.0-10.7 years) on ART. Long-term INR (LT-INR) was defined as failure to reach a CD4 T-cell count >350 cells per microliter. Marker stability was evaluated by parallel analysis of samples from ART-naïve and HIV-seronegative controls.
  
  
  RESULTS
  Baseline CD4 T-cell counts predicted subsequent LT-INR (n = 15) [odds ratio, 1.10 (95% confidence interval: 1.01 to 1.19) pr. 10 cells/μL reduction in CD4 count, P = 0.030] in the cohort as a whole, but not in patients with baseline CD4 counts <200 cells per microliter (n = 78). LT-INR was best characterized by elevated plasma levels of the CC chemokine macrophage inflammatory protein 1β (MIP-1β), both at baseline (pre-ART) and during ART. In patients with baseline CD4 counts <200 cells per microliter, baseline MIP-1β predicted LT-INR [odds ratio 1.23 (95% confidence interval: 1.02 to 1.47) per 10 pg/mL increase in MIP-1β, P = 0.029].
  
  
  CONCLUSIONS
  Elevated pre-ART levels of MIP-1β identified LT-INR patients who started ART at CD4 counts <200. INR was characterized by persistently high MIP-1β during suppressive ART. Thus, MIP-1β may be of use for early identification of LT-INR.
authors.affiliation: *Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; †Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ‡K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; §Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; ‖K.G. Jebsen Thrombosis Research and Expertise Center, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway; ¶Department of Immunology, Oslo University Hospital, Oslo, Norway; #Research Laboratory, Nordland Hospital, Bodø, Norway; **Center of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway; and ††Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.
authors.forename: Christian
authors.initials: C
authors.lastname: Prebensen
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.forename: Andreas
authors.initials: A
authors.lastname: Lind
authors.forename: Frank O
authors.initials: FO
authors.lastname: Pettersen
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Anne Ma
authors.initials: AM
authors.lastname: Dyrhol-Riise
authors.forename: Dag
authors.initials: D
authors.lastname: Kvale
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D054407:Chemokine CCL4 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; C066507:CCL4 protein, human; D054407:Chemokine CCL4; D012367:RNA, Viral