%0 Journal Article
%A Dominguez-Molina, Beatriz
%A Tarancon-Diez, Laura
%A Hua, Stephane
%A Abad-Molina, Cristina
%A Rodriguez-Gallego, Esther
%A Machmach, Kawthar
%A Vidal, Francesc
%A Tural, Cristina
%A Moreno, Santiago
%A Goni, Maria Jose
%A Ramirez-de-Arellano, Elena 
%A del-Val, Margarita
%A Gonzalez-Escribano, Maria Francisca
%A Del-Romero, Jorge
%A Rodriguez, Carmen
%A Capa, Laura
%A Viciana, Pompeyo
%A Alcami, Jose
%A Yu, Xu G.
%A Walker, Bruce D.
%A Leal, Manuel
%A Lichterfeld, Mathias
%A Ruiz-Mateos, Ezequiel
%T HLA-B(star)57 and IFNL4-Related Polymorphisms Are Associated With Protection Against HIV-1 Disease Progression in Controllers
%D 2017
%@ 1058-4838
%U http://hdl.handle.net/10668/18938
%X Human immunodeficiency virus type 1 ( HIV-1 ) controllers maintain HIV-1 viremia at low levels (normally <2000 HIV - RNA copies/mL) without antiretroviral treatment . However, some HIV-1 controllers have evidence of immunologic progression with marked CD4+  T-cell decline. We investigated host genetic factors associated with protection against CD4+  T-cell loss in HIV-1 controllers. Methods .We analyzed the association of interferon-lambda 4 (IFNL4)–related polymorphisms and human leukocyte antigen (HLA)-B haplotypes within long-term nonprogressor HIV-1 controllers (LTNP-Cs; defined by maintaining CD4+  T-cells counts >500 cells /mm3 for more than 7 years after HIV-1 diagnosis ) vs non-LTNP-Cs who developed CD4+  T-cell counts <500 cells /mm3. Both a Spanish study cohort (n = 140) and an international validation cohort (n = 914) were examined. Additionally, in a subgroup of individuals, HIV-1 –specific T-cell responses and soluble cytokines were analyzed.Results. HLA-B *57 was independently associated with the LTNP-C phenotype ( odds ratio [OR], 3.056 [1.029–9.069]; P = .044 and OR, 1.924 [1.252–2.957]; P = .003) while IFNL4 genotypes represented independent factors for becoming non-LTNP-C (TT/TT, ss469415590; OR, 0.401 [0.171–0.942]; P = .036 or A/A, rs12980275; OR, 0.637 [0.434–0.934]; P = .021) in the Spanish and validation cohorts, respectively, after adjusting for sex , age at HIV-1 diagnosis , IFNL4-related polymorphisms, and different HLA-B haplotypes . LTNP-Cs showed lower plasma induced protein 10 (P = .019) and higher IFN-γ (P = .02) levels than the HIV-1 controllers with diminished CD4+  T-cell numbers. Moreover, LTNP-Cs exhibited higher quantities of interleukin (IL)2+CD57- and IFN-γ +CD57-  HIV-1 –specific CD8+  T cells (P = .002 and .041, respectively) than non-LTNP-Cs.Conclusions.We defined genetic markers able to segregate stable HIV-1 controllers from those who experience CD4+  T-cell decline. These findings allow for identification of HIV-1 controllers at risk for immunologic progression and provide avenues for personalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.
%K HIV controllers
%K progression
%K HLA-B(star)57
%K IFNL4
%K Plasmacytoid dendritic cells
%K Elite
%K Il28b
%K Clearance
%K Therapy
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