Add-on Pyridostigmine Enhances CD4 T-Cell Recovery in HIV-1-Infected Immunological Non-Responders: A Proof-of-Concept Study.

BACKGROUND

In human immunodeficiency virus (HIV)-infection, persistent T-cell activation leads to rapid turnover and increased cell death, leading to immune exhaustion and increased susceptibility to opportunistic infections. Stimulation of the vagus nerve increases acetylcholine (ACh) release and modulates inflammation in chronic inflammatory conditions, a neural mechanism known as the (CAP). Pyridostigmine (PDG), an ACh-esterase inhibitor, increases the half-life of endogenous ACh, therefore mimicking the CAP. We have previously observed that PDG reduces activation and proliferation of T-cells obtained from people living with HIV.

METHODS

We conducted a 16-week proof-of-concept open trial using PDG as add-on therapy in seven HIV-infected patients with discordant immune response receiving combined antiretroviral therapy, to determine whether PDG would promote an increase in total CD4 T-cells. The trial was approved by the Institutional Research and Ethics Board and registered in ClinicalTrials.gov (NCT00518154).

RESULTS

Seven patients were enrolled after signing informed consent forms. We observed that addition of PDG induced a significant increase in total CD4 T-cells (baseline = 153.1 ± 43.1 vs. week-12 = 211.9 ± 61.1 cells/µL;  = 0.02). analysis showed that in response to PDG, four patients (57%) significantly increased CD4 T-cell counts (responders = 257.8 ± 26.6 vs. non-responders = 150.6 ± 18.0 cells/µL;  = 0.002), and the effect persisted for at least 1 year after discontinuation of PDG.

CONCLUSION

Our data indicate that in patients with HIV, add-on PDG results in a significant and persistent increase in circulating CD4 T-cells.