CD161⁺⁺/MAIT cells fail to recover with HAART. Patients with chronic-stage HIV infection were followed for 2 years of HAART, with samples taken before the start of treatment (T0), then at 1 year (T1) and 2 years (T2) into treatment (n = 29). PBMCs were stained for markers of interest including CD161, TCR Vα7.2 and CCR6, and a random selection were stimulated with PMA and ionomycin to analyze the production of IFNγ, IL17A and IL22 (n = 13). PBMCs from healthy controls were stained for surface markers of interest including CD161 (n = 23), TCR Vα7.2 (n = 15), and CCR6 (n = 15) or were stimulated with PMA and ionomycin to analyze the production of IFNγ, IL17A and IL22 (n = 23). (A) All HIV⁺ patients showed complete suppression of viral load and recovery of CD4⁺ T cells over the course of treatment. (B) There were no changes in the frequency of CD161⁺⁺CD8⁺ T cells or CD161⁺CD8⁺ T cells during treatment. (C) CD161⁺⁺Vα7.2⁺CD8⁺ T cells and IL17A-producing CD8⁺ T cells failed to recover over the course of treatment. Note data points in plots (B) and (C) lie on the x-axis (values of 0% were arbitrarily ascribed a value of 0.001% or 0.0001% so as to appear on the log scale). (D) There was a lower frequency of CCR6⁺CD8⁺ T cells in the HIV⁺ cohort at all treatment time points compared with healthy controls, and this population of cells failed to recover over the course of treatment. There was no difference in the frequency of CCR6⁺CD4⁺ T cells between healthy controls and the HIV⁺ cohort at any of the treatment time points, and no change in the frequency of these cells over the course of treatment.