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1.
Nat Commun ; 15(1): 178, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38212337

ABSTRACT

HIV remission can be achieved in some people, called post-treatment HIV controllers, after antiretroviral treatment discontinuation. Treatment initiation close to the time of infection was suggested to favor post-treatment control, but the circumstances and mechanisms leading to this outcome remain unclear. Here we evaluate the impact of early (week 4) vs. late (week 24 post-infection) treatment initiation in SIVmac251-infected male cynomolgus macaques receiving 2 years of therapy before analytical treatment interruption. We show that early treatment strongly promotes post-treatment control, which is not related to a lower frequency of infected cells at treatment interruption. Rather, early treatment favors the development of long-term memory CD8+ T cells with enhanced proliferative and SIV suppressive capacity that are able to mediate a robust secondary-like response upon viral rebound. Our model allows us to formally demonstrate a link between treatment initiation during primary infection and the promotion of post-treatment control and provides results that may guide the development of new immunotherapies for HIV remission.


Subject(s)
HIV Infections , Simian Acquired Immunodeficiency Syndrome , Simian Immunodeficiency Virus , Animals , Humans , Male , Simian Acquired Immunodeficiency Syndrome/drug therapy , CD8-Positive T-Lymphocytes , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Viral Load
2.
Biol Psychol ; 144: 115-124, 2019 05.
Article in English | MEDLINE | ID: mdl-30930071

ABSTRACT

Fatigue induced by sustained cognitive demands often entails decreased behavioural performance and the unavailability of brain resources, either due to reduced levels or impaired access. In the present study, we investigated the neural dynamics underlying preserved behavioural performance after inducing cognitive fatigue (CF) in a sleep deprivation (SD) condition in which resources are naturally compromised. Using functional near infrared spectroscopy (fNIRS), we recorded cortical brain activity during task-related CF induction in the evening, in the middle of the night and early in the morning. Although cortical oxygenation similarly increased over the 3 sessions, decreased intra-hemispheric connectivity between left anterior frontal and frontal areas paralleled a sudden drop in task performance in the early morning. Our data indicate that decreased sustained attention after the induction of cognitive fatigue in a situation of high sleep pressure results from impaired connectivity between left prefrontal cortical areas rather than from a mere modulation in brain resources.


Subject(s)
Cognitive Dysfunction/psychology , Fatigue/psychology , Prefrontal Cortex/diagnostic imaging , Sleep Deprivation/psychology , Task Performance and Analysis , Adult , Attention , Brain/diagnostic imaging , Brain/physiopathology , Cognition , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Fatigue/diagnostic imaging , Fatigue/physiopathology , Female , Humans , Male , Optical Imaging/methods , Prefrontal Cortex/physiopathology , Sleep , Sleep Deprivation/diagnostic imaging , Sleep Deprivation/physiopathology , Spectroscopy, Near-Infrared , Time Factors , Young Adult
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