title: Circulating biomarkers of immune activation distinguish viral suppression from nonsuppression in HAART-treated patients with advanced HIV-1 subtype C infection.
abstract: Few studies have examined immune activation profiles in patients with advanced HIV-1 subtype C infection or assessed their potential to predict responsiveness to HAART. BioPlex, ELISA, and nephelometric procedures were used to measure plasma levels of inflammatory biomarkers in HIV-1 subtype C-infected patients sampled before and after 6 months of successful HAART (n = 20); in patients failing HAART (n = 30); and in uninfected controls (n = 8). Prior to HAART, CXCL9, CXCL10, β 2M, sTNF-R1, TGF- β 1, IFN- γ , IL-6, TNF, and sCD14 were significantly elevated in HIV-1-infected patients compared to controls (P < 0.01). All of these markers, with the exception of sTNF-R1, were also elevated in patients failing HAART (P < 0.05). The persistently elevated levels of CXCL9, CXCL10, and β 2M in patients failing therapy in the setting of a marked reduction in these markers in patients on successful HAART suggest that they may be useful not only to monitor immune activation during HAART, but also to distinguish between good and poor responders. In the case of sCD14 and TGF- β 1, the levels of these biomarkers remained persistently elevated despite HAART-induced virological suppression, a finding that is consistent with ongoing monocyte-macrophage activation, underscoring a potential role for adjuvant anti-inflammatory therapy.
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Glen
authors.initials: G
authors.lastname: Malherbe
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Steel
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cassol
authors.affiliation: Africa Centre for Health and Population Studies, Mtubatuba 3935, South Africa.
authors.forename: Tulio
authors.initials: T
authors.lastname: de Oliveira
authors.affiliation: Jembi Health Systems NPC, Cape Town, Cape Town 7945, South Africa ; School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Westville 3600, South Africa.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Seebregts
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Ronald
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston MA02215, MA, USA.
authors.forename: Edana
authors.initials: E
authors.lastname: Cassol
authors.affiliation: Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Rossouw
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood*; D054357:Chemokine CXCL10 / Q000097:blood; D054370:Chemokine CXCL9 / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000097:blood*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D053773:Transforming Growth Factor beta1 / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma