CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naive for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = -0.46, p = 0.043) and of CCR6 (rho = -0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.We would like to thank all patients and healthy donors who participated in the study. This study has been funded by projects CP14/00198, PI16/01769, and RD16/0025/0013 integrated in the State Plan for Scientific and Technical Research and Innovation and co-funded by ISCIII-Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). N Rallon is a Miguel Servet investigator from the Spanish Carlos III Institute of Health (ISCIII), grant CP14/00198, Madrid, Spain. Maria Angeles Navarrete-Munoz was funded by RD16/0025/0013 and the Intramural Research Scholarship from IIS-FJD. Clara Restrepo was funded by project RD16/0025/0013. M Garcia is a predoctoral student co-funded by CP14/00198 project and the Intramural Research Scholarship from IIS-FJD.S

A model to predict the response to therapy against hepatitis C virus (HCV) including low-density lipoprotein receptor genotype in HIV/HCV-coinfected patients

Accurate prediction of sustained virological response (SVR) to pegylated interferon-a (Peg-IFN) plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients could improve the management of these patients. We aimed to develop a model to predict SVR to Peg-IFN/ribavirin in HIV/HCV-coinfected individuals combining HCV genotype and baseline HCV RNA load with interleukin 28B and low-density lipoprotein receptor genetic variations.Fil: Neukam, Karin. Hospital Universitario de Valme; EspañaFil: Almeida, Carmen. Hospital Universitario de Valme; EspañaFil: Caruz, Antonio. Universidad de Jaén; España;Fil: Rivero Juarez, Antonio. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; EspañaFil: Rallon, Norma. Hospital Carlos III. Departamento de Enfermedades Infecciosas; EspañaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Herrero, Rocío. Universidad de Jaén; España;Fil: Camacho, Angela. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; EspañaFil: Benito, José. Hospital Carlos III. Departamento de Enfermedades Infecciosas; EspañaFil: Macias, Juan. Hospital Universitario de Valme; EspañaFil: Rivero, Antonio. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; EspañaFil: Soriano, Vicente. Hospital Carlos III. Departamento de Enfermedades Infecciosas; EspañaFil: Pineda, Juan Antonio. Hospital Universitario de Valme; Españ

Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in HIV/HCV-coinfected patients with all HCV genotypes

Background. A recent genome-wide association study reported a strong association with a single-nucleotide polymorphism (SNP) in the inosine triphosphate (ITPA) gene and hemolytic anemia in patients infected with hepatitis C virus (HCV) receiving pegylated interferon and ribavirin. We investigate these polymorphisms in a cohort of human immunodeficiency virus (HIV)/ HCV-coinfected patients

Effects of the genetic pattern defined by low-density lipoprotein receptor and IL28B genotypes on the outcome of hepatitis C virus infection

The aim of this study was to assess the impact of the genetic pattern (GP) defined by the single nucleotide polymorphisms (SNPs) rs14158 of low-density lipoprotein receptor (LDLR) and rs12979860 of interleukin-28B (IL28B) genes on the outcome and features of hepatitis C virus (HCV) infection in patients with and without human immunodeficiency virus (HIV) coinfection. 314 HIV/HCVcoinfected and 109 HCV-monoinfected patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV), as well as 51 patients with HCV spontaneous clearance (SC), were included. Variations in both SNPs were determined by the TaqMan polymerase chain reaction (PCR) assay. In the 286 patients chronically infected by HCV genotypes 1 or 4, both rs14158 CC and rs12979860 CC were associated with a higher rate of sustained virological response (SVR), and these effects were complementary in both HCVmonoinfected and HIV/HCV-coinfected patients. Thus, 24 % of patients with rs14158/rs12979860 TT-TC/TT-TC, 33 % with TT-TC/CC, 44.2 % with CC/TT-TC, and 75.8 % harboring CC/CC attained SVR (p< 0.001). SC was associated with the IL28B genotype (66.7 % CC in SC vs. 42.6 % among those with chronic infection, p < 0.001) but not with the LDLR genotype. There was no association between GP and the plasma level of alanine aminotransferase (ALT) or the presence of advanced fibrosis. There is a complementary effect between the IL28B and LDLR genotypes on the probability of achieving SVR after Peg-IFN/RBV therapy in patients with HCV 1 or 4. Thus, the predictive value of IL28B genotype is modulated by the LDLR genotype in both HCV-monoinfected and HIV/HCV-coinfected patients. This complementary effect of both genotypes is also observed on the plasma levels of low-density lipoprotein cholesterol (LDL-C).Fil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina; Hospital Universitario Valme. Unidad de Enfermedades Infecciosas y Microbiología; España; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;Fil: Caruz, Antonio. Universidad de Jaén; España;Fil: Rallon, Norma I.. Hospital Carlos III. Departamento de Enfermedades Infecciosas. Unidad de Inmunogenética; España;Fil: Rivero Juarez, Antonio. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; España;Fil: Neukam, Karin. Hospital Universitario Valme. Unidad de Enfermedades Infecciosas y Microbiología; España;Fil: Barreiro, Pablo. Hospital Carlos III. Departamento de Enfermedades Infecciosas. Unidad de Inmunogenética; España;Fil: Camacho, Angela. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; España;Fil: Garcia Rey, Silvia. Hospital Universitario Valme. Unidad de Enfermedades Infecciosas y Microbiología; España;Fil: Rivero, Antonio. Hospital Universitario Reina Sofía. Instituto Maimónides de Investigación Biomédica de Córdoba. Unidad de Enfermedades Infecciosas; España;Fil: Soriano, Vicente. Hospital Carlos III. Departamento de Enfermedades Infecciosas. Unidad de Inmunogenética; España;Fil: Cifuentes, Celia. Hospital Universitario Valme. Unidad de Enfermedades Infecciosas y Microbiología; España;Fil: Macias, Juan. Hospital Universitario Valme. Unidad de Enfermedades Infecciosas y Microbiología; España;Fil: Pineda, Juan A.. Hospital Universitario Valme. Unidad de Enfermedades Infecciosas y Microbiología; España

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection.

HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by in vitro intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of env and gag genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r = -0.8; P = 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.IMPORTANCE There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.Funding for this research was provided by: Gilead Sciences (GLD14/293 GLD15/00298) Instituto de Salud Carlos III (PT13/001/0028, PI12/02283 PI13/01912 PI13/02269 PI14/01058 PI10/2635 PI13/0796 PI16/0503 PI16CIII/0034, CPII15/00014, PI12/00506 PI12/00969 PI15/00480 PI16/00684 CPII014/00025, RD16/0025/0020, RD12/0017/0002 RD12/0017/0005 RD12/0017/0029 RD12/0017/0036 RD12/0017/0037 RD 16CIII/0002/0005, INT15/226, RD12/0017/0036, Joan Rodes, FI14/00431, RD12/0017/0037) Ministerio de Economía y Competitividad (SAF 2010-17226 SAF 2016-77894-R, FPU13/02451)S