A novel measure of antiretroviral activity in cerebrospinal fluid and association with HIV persistence and cognitive...

HIV has been shown to persist in cerebrospinal fluid (CSF) in persons on antiretroviral therapy (ART), which may be linked with inadequate ART exposure, potentially contributing to neurocognitive dysfunction. Our objective was to compare ART regimen inhibitory activity in CSF with participant outcomes.

A5321 is a prospective study of HIV reservoirs among persons with HIV on long-term ART with documented suppressed viremia; 44 participants who underwent lumbar puncture were evaluated. CSF trough concentrations were determined and inhibitory quotients (IQs) calculated for each antiretroviral (ARV) in a participant's regimen as the ratio of CSF concentration to literature values for in vitro HIV IC 50or90 . The geometric mean (GM) of CSF IQs of all drugs in each participant's ART regimen was calculated (CSF ART-IQ GM ). Statistical analyses evaluated associations among ART-IQ GM and CSF HIV DNA, biomarkers and global deficit score (GDS).

The median (Q1, Q3) CSF ART-IQ GM was higher in those with undetectable vs. detectable CSF cell-associated HIV DNA (CA-DNA): 0.9 (0.5, 1.6) vs. 0.5 (0.3, 0.9), P  = 0.027. Higher ART-IQ GM was associated with lower GDS (i.e., better global cognitive function, Spearman: -0.30, P  = 0.05). There was no association between CSF inflammatory biomarkers and ART-IQ GM .

The CSF ART-IQ GM is a novel approach to assess ART regimen activity. This metric was associated with lack of CSF CA-DNA detection and better GDS, which suggests ART regimen activity affects HIV persistence in CSF. This tool motivates further investigations of relationships between regimen activity and biomarkers of HIV persistence in CSF and in other anatomic HIV reservoirs.