T Cell Activation Is Associated with Lower CD4⁺T Cell Gains in Human Immunodeficiency Virus–Infected Patients with Sustained Viral Suppression during Antiretroviral Therapy

TLDR

T cell activation is linked to disease progression in untreated HIV‑1, but its impact during antiretroviral therapy is unclear. The study proposes that targeting T cell activation could serve as an adjunct to antiretroviral therapy. The authors quantified CD38⁺HLA‑DR⁺ T cell counts in 99 HIV‑infected adults with sustained viral suppression on antiretroviral therapy. In treated patients, persistent T cell activation is associated with reduced CD4⁺ gains, shorter viral suppression, HCV coinfection, frequent low‑level viremia, and lower nadir CD4 counts, with each 5 % increase in activated CD8⁺ cells linked to 35 fewer CD4⁺ cells gained.

Abstract

Although T cell activation is associated with disease progression in untreated human immunodeficiency virus type 1 (HIV-1) infection, its significance in antiretroviral-treated patients is unknown. Activated (CD38+HLA-DR+) T cell counts were measured in 99 HIV-infected adults who had maintained a plasma HIV RNA level ⩽1000 copies/mL for a median of 21 months while receiving antiretroviral therapy. Patients with sustained viral suppression had lower levels of T cell activation than untreated patients but higher levels than HIV-uninfected control subjects. Persistent T cell activation was associated with decreased CD4+ T cell gains during therapy. For every 5% increase in the proportion of activated CD8+ T cells, 35 fewer CD4+ T cells/mm3 were gained. Increased T cell activation was associated with shorter duration of viral suppression, hepatitis C virus coinfection, frequent low-level viremia, and lower nadir CD4+ T cell counts. Interventions that directly target T cell activation or the determinants of activation may prove to be useful adjuvants to antiretroviral therapy