Brain extracellular free water may signal neuroinflammation in HIV

Brain extracellular free water (FW) appears to be a useful biomarker for monitoring HIV-associated neuroinflammation, a recent study has found.

The study included 96 age-matched participants: 44 with HIV (mean age 34.48±1.95 years, 90.9 percent men) and 52 without (mean age 37.02±1.66 years, 50 percent men). All participants underwent neuropsychological assessments and magnetic resonance imaging, which was used in the calculation of extracellular FW.

Gray matter (GM; p<0.001) and white matter (WM; p=0.014) extracellular FW decreased significantly after 12 weeks of combination antiretroviral treatment (cART). Short-term linear mixed effects modelling also found that GM and WM were significantly correlated with higher FW among HIV+ participants (p<0.001 and p=0.004, respectively).

Long-term analysis that compared 1-year to 12-week outcomes and baseline parameters found that FW was significantly increased in WM and GM in HIV+ vs HIV– participants.

In terms of blood markers, the researchers found an inverse correlation between CD4 cell counts and FW in GM and WM. On the other hand, FW in GM and WM was positively associated with neurofilament light chain levels.

Notably, the cognitive score was inversely correlated with FW for WM and GM at baseline, though the interaction failed to reach significance.

“[O]ur findings suggest that extracellular FW is elevated in the brains of cART-naïve HIV+ participants at a time when neuroinflammation is expected to be high. Higher levels of NfL and low CD4 counts and their correlations with FW tend to support this possibility,” the researchers said. “Most importantly, short-term cART treatment effectively reduces the levels of FW and stabilizes it over 2 years of follow-up.”

Future longitudinal studies enrolling larger samples are needed to confirm these findings.