RT Journal Article
T1 Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection
A1 Pernas, Maria
A1 Tarancon-Diez, Laura
A1 Rodriguez-Gallego, Esther
A1 Gomez, Josep
A1 Prado, Julia G.
A1 Casado, Concepcion
A1 Dominguez-Molina, Beatriz
A1 Olivares, Isabel
A1 Coiras, Maite
A1 Leon, Agathe
A1 Rodriguez, Carmen
A1 Benito, Jose Miguel
A1 Rallon, Norma
A1 Plana, Montserrat
A1 Martinez-Madrid, Onofre
A1 Dapena, Marta
A1 Iribarren, Jose Antonio
A1 del Romero, Jorge
A1 Garcia, Felipe
A1 Alcami, Jose
A1 Munoz-Fernandez, MaAngeles
A1 Vidal, Francisco
A1 Leal, Manuel
A1 Lopez-Galindez, Cecilio
A1 Ruiz-Mateos, Ezequiel
A1 ECRIS Integrated Spanish AIDS Res, 
K1 HIV-1 elite controllers
K1 T-cell response
K1 viral diversity
K1 inflammatory biomarkers
K1 HIV-1 controllers
K1 inflammation
K1 Immunodeficiency-virus type-1
K1 Cd8(+) t-cells
K1 Viral load
K1 Evolution
K1 Suppression
K1 Rantes
K1 Rates
K1 Nonprogressors
K1 Heterogeneity
K1 Polymorphism
AB 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.
PB Amer soc microbiology
SN 0022-538X
YR 2018
FD 2018-03-01
LK http://hdl.handle.net/10668/19026
UL http://hdl.handle.net/10668/19026
LA en
DS RISalud
RD Apr 8, 2025