Mechanisms of abrupt loss of virus control in a cohort of previous HIV controllers

Miriam Rosás-Umbert, Anuska Llano, Rocío Bellido, Alex Olvera, Marta Ruiz-Riol, Muntsa Rocafort, Marco A. Fernández, Patricia Cobarsi, Manel Crespo, Lucy Dorrell, Jorge Del Romero, José Alcami, Roger Paredes, Christian Brander, Beatriz Mothe

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    8 Citations (Scopus)

    Abstract

    Copyright © 2019 Rosás-Umbert et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Elite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control. The in-depth analysis of these subjects involved the study of cell tropism of circulating virus, evidence for HIV superinfection, cellular immune responses to HIV, as well as an examination of viral adaptation to host immunity by Gag sequencing. Our data demonstrate that a poor capacity of T cells to mediate in vitro viral suppression, even in the context of protective HLA alleles, predicts a loss of viral control. In addition, the data suggest that inefficient viral control may be explained by an increase of CD8 T-cell activation and exhaustion before LoC. Furthermore, we detected a switch from C5- to X4-tropic viruses in 4 individuals after loss of control, suggesting that tropism shift might also contribute to disease progression in HIV controllers. The significantly reduced inhibition of in vitro viral replication and increased expression of activation and exhaustion markers preceding the abrupt loss of viral control may help identify untreated HIV controllers that are at risk of losing control and may offer a useful tool for monitoring individuals during treatment interruption phases in therapeutic vaccine trials.
    Original languageEnglish
    Article numbere0143618
    JournalJournal of Virology
    Volume93
    DOIs
    Publication statusPublished - 1 Feb 2019

    Keywords

    • Cell tropism
    • HIV-1 control
    • HIV-1 progression
    • Host genetics
    • In vitro virus inhibition
    • Loss of control

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