Kinetics of plasma cytokines and chemokines during primary HIV-1 infection and after analytical treatment interruption

Abstract

Background: There are strong theoretical arguments for initiating antiretroviral therapy (ART) during primary HIV-1 infection (PHI) to preserve HIV-1-specific T-cell responses and to decrease immune activation.

Methods: We assessed the degree of immune activation during PHI and after analytical treatment interruption (ATI) in plasma samples from 22 subjects by measuring 13 cytokines/chemokines with the Luminex system. Subjects initiated quadruple ART at PHI (the QUEST cohort) and were classified as responders or nonresponders according to their HIV-1 viral load (VL) 6 months post-ATI.

Results: During PHI, nonresponders had higher levels of HIV-1 RNA, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10 and eotaxin than responders (P</=0.05). A positive correlation was found between VL and IFN-alpha, TNF-alpha, IL-1beta, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, respectively. Post ATI, responders had higher levels of IFN-gamma, MIP-1beta and monocyte chemotactic protein (MCP)-1 than nonresponders, while nonresponders had higher levels of HIV-1 RNA, IL-15 and eotaxin. Cytokine/chemokine levels were higher during PHI than post-ATI.

Conclusions: High levels of immune activation during PHI are associated with a worse virological outcome post-ATI. In contrast, VL post-ATI is negatively correlated with IFN-gamma and chemokines. Therefore, the degree of immune activation during PHI is associated with both the VL at PHI and the viral set-point post-ART.