Galantamine for 12 weeks does not improve neurocognition or immune activation in ART-suppressed people with HIV.

OBJECTIVE

People with HIV on ART are highly vulnerable to non-AIDS-related comorbidities, including HIV-associated neurocognitive disorders, which are linked to persistently activated monocytes/macrophages. Smoking is a major contributor to HIV-related comorbidities. However, nicotine alone has anti-inflammatory effects, mainly through α7-nicotinic receptor (nAChR) activation. Galantamine (GAL) is an FDA-approved pro-cognitive medication that increases endogenous acetylcholine and also directly potentiates the α7-nAChR. We hypothesized that GAL would improve neurocognition in PWH, both by direct pro-cognitive effects and by reducing inflammation. We also explored whether effects differed by smoking status.

DESIGN/

METHODS

Smoking and nonsmoking PWH/ART participated in a double-blind, randomized, placebo-controlled crossover study of 12 weeks of GAL treatment. Primary outcomes were composite neurocognitive test score; monocyte CD16, CD163 and CCR2, and CD8 T-cell CD38/HLA-DR; and plasma sCD16, sCD163 and CCL2. Plasma hsCRP and neurofilament light chain (NFL) were also measured. Exploratory analyses included plasma mediators by Luminex and monocyte transcriptome by RNAseq.

RESULTS

Neurocognition did not differ between GAL and placebo treatment (adjusted standardized difference (95% CI) -0.02 (-0.2, 0.2); P  = 0.82), with no difference by smoking status ( P  = 0.51). Monocyte CCR2 expression was 15.2% (5, 25.1) greater with GAL than placebo ( P  = 0.006). No differences were seen in monocyte CD16 ( P  = 0.76) or CD163 ( P  = 0.8), CD8 + T-cell CD38/HLA-DR ( P  = 0.54), or plasma sCD163 ( P  = 0.36), sCD14 ( P  = 0.46), or CCL2 ( P  = 0.34). NFL and hsCRP were not different, but several pro-inflammatory cytokines increased with GAL. Only modest effects were seen on monocyte gene expression.

CONCLUSIONS

Galantamine for 12 weeks did not improve cognition or reduce inflammation in PWH/ART regardless of smoking status.