Impact of extended-release niacin on immune activation in HIV-infected immunological non-responders on effective antiretroviral therapy.

BACKGROUND

Background

Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) is involved in immune dysregulation during HIV infection. Niacin (vitamin B3) could control the excess of tryptophan depletion and represents a potential strategy to improve immune functions and CD4 count recovery in immunological non-responder HIV-infected individuals on antiretroviral therapy (ART).

METHODS

Methods

In the CTN PT006 phase 2 pilot randomized trial, 20 adults on ART with CD4 ≤ 350 cells/µl, despite an undetectable viral load (VL) for at least 3 months, received 2000 mg of extended-release (ER)-niacin orally once daily for 24 weeks. Side effects, VL, CD4/CD8 counts, lipid profile, T-cell activation and senescence, Tregs and Th17 cell frequencies, Kyn/Trp ratio, and levels of IL-6, IP-10, sST2, I-FABP, and LBP were assessed following ER-niacin treatment.

RESULTS

Results

Thirteen participants completed the study. Treatment was interrupted in 4 patients due to loss of follow-up or personal reasons and 3 patients were discontinued due to comorbidity risks. All participants maintained a VL < 40 copies/ml, while ER-niacin did not affect CD4 and CD8 cell counts. Plasma levels of triglycerides, total, and LDL cholesterol significantly decreased, following ER-niacin treatment. ER-niacin also diminished Kyn plasma levels and slightly decreased CD4 T-cell activation. However, no improvement in CD8 subsets, Kyn/Trp ratio, Th17/Treg balance, and plasma inflammatory markers was observed.

CONCLUSIONS

Conclusions

Although ER-niacin combined with ART was well-tolerated among immune non-responders and decreased plasma lipids, it did not improve systemic inflammation, Kyn/Trp ratio, and CD4 cell recovery. Overall, ER-niacin was not effective to overcome chronic inflammation in PLWH.