RT info:eu-repo/semantics/article
T1 HLA-B*57 and IFNL4-Related Polymorphisms Are Associated With Protection Against HIV-1 Disease Progression in Controllers.
A1 Valenzuela Fernández, Agustín
A1 Dominguez Molina, Beatriz
A1 Ruiz Mateos, Ezequiel
K1 HIV controllers
K1 HLA-B*57
K1 IFNL4
AB Background. Human immunodeficiency virus type 1 (HIV-1) controllers maintain HIV-1 viremia at low levels (normally <2000HIV-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 inHIV-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 subgroupof 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 = .044and 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 validationcohorts, 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 withdiminished 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-celldecline. These findings allow for identification of HIV-1 controllers at risk for immunologic progression and provide avenues forpersonalized therapeutic interventions and precision medicine for optimizing clinical care of these individuals.
SN 1537-6591
YR 2016
FD 2016
LK http://riull.ull.es/xmlui/handle/915/35364
UL http://riull.ull.es/xmlui/handle/915/35364
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 11-jun-2024