Neuroaxonal Injury in Acute HIV Infection and Following Immediate Antiretroviral Therapy

Abstract

Introduction: This study evaluates the degree of neuroaxonal injury during acute HIV infection (AHI) in neuroasymptomatic individuals and the neuroprotective effect of antiretroviral therapy (ART) initiated during AHI, by measuring neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) samples collected during pre-ART AHI and at post-ART visits up to 5 years.

Methods: RV254 cohort participants (99% male, median age 27 years) were enrolled during Fiebig I-V AHI. A subset completed optional lumbar punctures during pre-ART AHI (week 0, n=136) and/or at post-ART visits with HIV suppression (weeks 24, 48, 96 and 240, n=201). RV254 CSF NFL measurements were compared to those of 44 people without HIV (PWoH), both adjusted to a sampling age of 30, and to age-based upper normal limits (UNL).

Outcomes: RV254 participants demonstrated higher CSF NFL than PWoH at pre-ART AHI (p<0.001), and post-ART weeks 24 (p<0.001) and 48 or later (week 48+, p=0.003). CSF NFL was elevated (i.e., >UNL) in 15%, 8% and 7% of RV254 participants at weeks 0, 24, and 48+ respectively, versus 2% among PWoH.During AHI, elevated CSF NFL was associated with later Fiebig stages (III-V) (p=0.034), higher CSF HIV RNA (p=0.012) and a smaller difference between HIV RNA in the plasma and CSF (p=0.002). Additionally, CSF NFL increased with GFAP and sTREM2 during pre-ART AHI and post-ART visits (p<0.050).

Conclusions: CNS injury may occur during AHI. Additionally, early ART alone is likely insufficient to provide complete neuroprotection.

Keywords: Acute HIV infection; RV254; antiretroviral therapy; cerebrospinal fluid; neuroaxonal injury; neurofilament light.