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Immune activation during acute HIV infection and the impact of early antiretroviral therapy

Krebs, Shelly J.; Ananworanich, Jintanat

Current Opinion in HIV and AIDS: March 2016 - Volume 11 - Issue 2 - p 163–172
doi: 10.1097/COH.0000000000000228
IMMUNE ACTIVATION: Edited by Irini Sereti and Marcus Altfeld

Purpose of review The purpose of this review is to outline recent data pertaining to mechanisms of immune activation in acute infection and describe new developments that seek to determine if early antiretroviral treatment can mitigate chronic immune activation.

Recent findings Following the detection of HIV RNA, highly activated CD8+ T cells expand and peak approximately 2 weeks following peak viral load whereas levels of proinflammatory soluble markers coincide with a rise in viral load. Immune activation during acute infection is driven by many factors including pyroptosis, replicative capacity of the infecting virus, and loss of Th17 cells within the gut. Early antiretroviral therapy (ART), particularly if initiated in Fiebig I (HIV IgM−), preserved mucosal CD4+ T cells, possibly preventing the release of microbial products associated with immune activation. Viral reservoirs were restricted by the early initiation of ART, and heightened systemic immune activation was partially prevented compared with chronic HIV infection. A strong correlation was found between the size of the viral reservoir and cellular immune activation.

Summary The timing of immune activation during acute infection occurs shortly after exposure. Recent studies demonstrated that ART mitigates inflammatory responses, preserves CD4+ T cells, and limits reservoir seeding if provided early in acute HIV infection.

aUS Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

bHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA

Correspondence to Shelly J. Krebs, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Tel: +1 301 319 3961; e-mail:

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