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

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 <or=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/mm(3) 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.

Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation

“…1A. As reported by others (21,22), both CD4 and CD8 cells showed increased CD38/ HLA-DR expression in ART 2 patients (p = 0.0007 and p , 0.0001, respectively), which was significantly decreased in ART + patients (p = 0.01 and p = 0.0005, respectively) (Fig. 1B).…”

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

“…Third, immune activation (largely measured as increased expression of CD38 þ and HLA-DR þ on T-cells) has also been shown to be inversely correlated with IL-7Ra expression on CD4 T-cells in HIV-infected patients, 45,46 and immune activation has a negative impact on CD4 T-cell recovery. [47][48][49] Although we did not compare the immune activation levels in the UARTO and Caucasian patients, numerous studies have described a higher degree of immune activation both in HIVuninfected [50][51][52][53][54] and HIV-infected African patients [53][54][55][56] as compared with patients from high-income countries owing to differences in the environment 52 and prevalence of other co-infections. 51 The combined effects of poorer CD4 T-cell gain owing to increased T-cell activation and a reduced expression of IL-7Ra on T-cells may potentially negate any beneficial effects of increased IL-7 availability.…”

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

“…Acute malaria infection may also be associated with an enhanced cellular activation state. Co-expression of CD38/HLA-DR on T cell subsets has previously been studied in both HIV-1/AIDS or malaria alone (Hunt et al 2003, Eggena et al 2006, Naniche et al 2011) and immune activation was considered a predictor of treatment failure in malaria patients (Eggena et al 2006). Malaria infection can present with a pro-inflammatory response and cytokine imbalance (Ayimba et al 2011, Davenport et al 2012.…”