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J Infect Dis. 2019 Jan 21. doi: 10.1093/infdis/jiz030. [Epub ahead of print]

Very early ART initiation during acute HIV infection is associated with normalization of cerebrospinal fluid but not plasma markers of immune activation.

Author information

1
Memory and Aging Center, Department of Neurology, University of California, San Francisco, California, USA.
2
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
3
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
4
SEARCH, Thai Red Cross AIDS Research Center, Bangkok, Thailand.
5
Department of Global Health, The University of Amsterdam, Amsterdam, The Netherlands.
6
Department of Biostatistics and Epidemiology, University of California, San Francisco.
7
Yale School of Medicine, New Haven, Connecticut, USA.

Abstract

Background:

Chronic immune activation in the blood and central nervous system are consequences of HIV infection that contribute to disease morbidity, and can occur despite virally-suppressive antiretroviral therapy (ART). The trajectory of HIV-related inflammation may vary with the timing of ART initiation. We examined cerebrospinal fluid (CSF) versus blood immune activation markers over 96 weeks in participants who initiated ART during acute HIV infection (AHI).

Methods:

RV254/SEARCH010 AHI participants underwent CSF (n=89) and plasma (n=146) sampling before initiating ART, and then at 24 and 96 weeks of treatment. Participants received a standard ART regimen, or this regimen plus maraviroc and raltegravir (ART+) for the first 24 weeks. We measured neopterin, CXCL10, CCL2, and IL6, compared with healthy, uninfected controls (n=18).

Results:

Following 24 and 96 weeks of treatment, all CSF markers normalized for AHI participants, while several plasma markers remained elevated (p<0.001). Participants receiving the ART+ regimen had lower median plasma CCL2 levels at week 24, and at week 96 had lower plasma neopterin levels.

Conclusions:

ART initiation during AHI differentially impacts the brain compartment, normalizing CSF but not plasma markers of inflammation, sustained at 96 weeks.

PMID:
30668739
DOI:
10.1093/infdis/jiz030

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