Abstract
BackgroundAntiretroviral therapy (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 have not been extensively evaluated.MethodsT-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were 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 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].ResultsBoth 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+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, 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, 1.1-2.1), P = 0.022].ConclusionT-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
Highlights
IntroductionAntiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection
Background antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection, abnormalities of immune activation markers persist in many patients [1,2,3]
This study reports the levels of T-cell immune activation and T-cell exhaustion among adult Ugandans with sustained HIV-RNA viral suppression after 4 years of Antiretroviral therapy (ART)
Summary
Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection, abnormalities of immune activation markers persist in many patients [1,2,3]. Up to 40% of individuals receiving ART have suboptimal CD4 T-cell recovery despite sustained HIV-RNA viral suppression [5,6,7]. There is conflicting data on the influence of T-cell activation on CD4 T-cell recovery among patients on successful ART [9,10]. There is limited data on the influence of immune activation on CD4 count and functional recovery with sustained HIV-RNA suppression in African populations [11,12], where endemic co-infections may dampen the immune response [13]
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