Class-modeling analysis reveals T-cell homeostasis disturbances involved in loss of immune control in elite controllers

Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. Methods A case–control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares–class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. Results Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. Conclusions These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials.projects RD12/0017/0031, RD16/0025/ 0013, and SAF2015-66193-R as part of the Health Research and Development Strategy, State Plan for Scientific and Technical Research and Innovation (2008– 2011 and 2013–2016) and cofinanced by the Institute of Health Carlos III (ISCIII), Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund. NR is a Miguel Servet investigator from the ISCIII (CP14/00198), Madrid, Spain. C Restrepo was funded by project RD12/0017/ 0031 and is currently funded by project RD16/0025/0013. M García is a predoctoral student co-funded by grant CP14/00198 and an Intramural Research Scholarship from Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD)

Interferon-stimulated genes are associated with peginterferon/ribavirin treatment response regardless of IL28B alleles in hepatitis C virus/HIV-coinfected patients

6.557 JCR (2013) Q1, 16/144 Immunology, 4/70 Infectious diseases, 3/32 Virolog

Knock-out IFNL4 gene variant is associated with protection from sexually transmitted HIV-1 infection

The IFNL4 knock-out allele (rs368234815-TT) is associated with spontaneous and IFNA-dependent cure of HCV. The role of this polymorphism in susceptibility to HIV-1 infection is controversial. This study is aimed to assess the association of this knock-out IFNL4 gene variant and sexually transmitted HIV-1 infection. 228 HIV-1 positive and 136 HIV-exposed seronegatives were investigated for their association with IFNL4 rs368234815 genotypes. The IFNL4 G functional allele is associated to increased susceptibility to HIV-1 infection through sexual route OR: 2.1 95% CI (1.2-3.6), P=0.004. A meta-analysis including an IDU population suggests a codominant mode of inheritance of this risk factor OR: 2.0 95% CI (1.3-3.2), P=0.001