Paper # 572|
High T Cell Immune Activation and Immune Exhaustion among ART-treated Patients with Suboptimal CD4 Recovery Despite Long-term Viral Suppression in an African Cohort
Damalie Nakanjako*1, I Ssewanyana2, H Mayanja-Kizza1, A Kiragga1,3, R Colebunders4, Y Manabe1,3, R Nabatanzi2, M Kamya1, and H Cao5
1Makerere Univ Sch of Med, Kampala, Uganda; 2Joint Clin Res Ctr, Kampala, Uganda; 3Infectious Disease Inst, Kampala, Uganda; 4Inst of Tropical Med, Univ of Antwerp, Belgium; and 5California Dept of Publ Hlth, Richmond, US
Background: ART partially corrects immune
dysfunction associated with HIV infection. The levels of T cell immune
activation and exhaustion after long-term, suppressive ART and their
correlation with CD4 T cell count reconstitution among ART-treated patients in
African cohorts has not been extensively evaluated.
Methods: T cell activation (CD38+HLA-DR+)
and immune exhaustion (PD-1+) was measured in a prospective cohort
of patients initiated on ART; 128
patient samples were evaluated and subcategorized by CD4 reconstitution after
long-term suppressive treatment: suboptimal (median CD4 count increase 165 [43
to 298] cells/μL, N = 44), optimal (297 [94 to 435] cells/μL, N = 59)
and super-optimal (564 [299 to 878] cells/μL, N = 25).
Results: Both CD4+ and CD8 T cell
activation was significantly higher among suboptimal CD4 T cell responders
compared to super-optimal responders. In a multivariate model, CD4+CD38+HLA-DR+
T cells were associated with suboptimal CD4 reconstitution (AOR, 5.7 [95%CI 1.4
to 23, p = 0.014]). T cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher
among suboptimal relative to optimal (p <0.001) and super-optimal
responders (p <0.001). T cell exhaustion was significantly associated
with suboptimal responders (AOR, 1.5 [95%CI, 1.1 to 2.1], p = 0.022).
Conclusions: T-cell activation and exhaustion persist
among HIV-infected patients despite long-term, sustained HIV-RNA viral
suppression. These parameters were associated with suboptimal CD4
reconstitution. Early initiation of ART prior to substantial immune damage may
be required to optimize treatment outcomes.