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

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.