AIDS (London, England) · 2025
Galantamine for 12 weeks does not improve neurocognition or immune activation in ART-suppressed people with HIV.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Yadav Anjana, Stephens-Shields Alisa J, Karaj Antoneta, Kossenkov Andrew V, Kannan Toshitha, Putt Mary E, Collman Ronald G, Ashare Rebecca L
Аннотация
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.
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.