Background. Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency.

Methods. We compared percentages of activated (CD38⁺HLA-DR⁺) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels.

Results. Although the median CD4⁺ cell count in controllers was 727 cells/mm³, 3 (10%) had CD4⁺ cell counts <350 cells/mm³ and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4⁺ and CD8+ cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8⁺ cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4⁺ and CD8⁺ T cell activation was associated with lower CD4⁺ cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P < .001), and in controllers higher LPS level was associated with higher CD8⁺ T cell activation (P = .039).

Conclusions. HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4⁺ T cell loss even without measurable viremia.