Abstract:
Chronic HIV infection is characterized by persistent inflammation despite antiretroviral therapy (ART). Cannabinoids may help reduce systemic inflammation in people with HIV (PWH). To assess the effects of oral cannabinoids during HIV, ten PWH on ART were randomized (n = 5/group) to increasing doses of oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (2.5:2.5-15:15 mg/day) capsules or CBD-only (200-800 mg/day) capsules for 12 weeks. Blood specimens were collected prospectively 7-21 days prior to treatment initiation and at weeks 0 to 14. Plasma cytokine levels were determined via Luminex and ELISA. Immune cell subsets were characterized by flow cytometry. HIV DNA/RNA were measured in circulating CD4 T-cells and sperm by ultra-sensitive qPCR. Results from both arms were combined for statistical analysis. Plasma levels of IFN-γ, IL-1β, sTNFRII, and REG-3α were significantly reduced at the end of treatment (p ˂ 0.05). A significant decrease in frequencies of PD1+ memory CD4 T-cells, CD73+ regulatory CD4 T-cells, and M-DC8+ intermediate monocytes was also observed (p ˂ 0.05), along with a transient decrease in CD28-CD57+ senescent CD4 and CD8 T-cells. Ki-67+ CD4 T-cells, CCR2+ non-classical monocytes, and myeloid dendritic cells increased over time (p ˂ 0.05). There were no significant changes in other inflammatory markers or HIV DNA/RNA levels. These findings can guide future large clinical trials investigating cannabinoid anti-inflammatory properties.
摘要:
尽管进行了抗逆转录病毒治疗(ART),但慢性HIV感染的特征是持续的炎症。大麻素可能有助于减少HIV(PWH)患者的全身性炎症。为了评估艾滋病毒期间口服大麻素的影响,10个ARTPWH被随机分配(n=5/组),以增加剂量的口服Δ9-四氢大麻酚(THC):大麻二酚(CBD)组合(2.5:2.5-15:15mg/天)胶囊或仅CBD(200-800mg/天)胶囊,持续12周。在治疗开始前7-21天和第0-14周前瞻性收集血液样本。通过Luminex和ELISA测定血浆细胞因子水平。通过流式细胞术表征免疫细胞亚群。通过超敏感qPCR测量循环CD4T细胞和精子中的HIVDNA/RNA。将两组的结果合并进行统计分析。IFN-γ的血浆水平,IL-1β,sTNFRII,治疗结束时REG-3α显著降低(p<0.05)。PD1+记忆CD4T细胞的频率显着降低,CD73+调节性CD4T细胞,并且还观察到M-DC8+中间单核细胞(p<0.05),伴随着CD28-CD57+衰老CD4和CD8T细胞的短暂减少。Ki-67+CD4T细胞,CCR2+非经典单核细胞,髓样树突状细胞随时间增加(p<0.05)。其他炎症标志物或HIVDNA/RNA水平没有显著变化。这些发现可以指导未来研究大麻素抗炎特性的大型临床试验。