Immunological factors associated with discordant virological response postcombination antiretroviral therapy in pediatric human immunodeficiency virus infection.

Abstract

Evaluation of immunological factors responsible for discordant virological responses postcombination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-positive children aged <5 years. Immunological profiling of enrolled 30 HIV-positive children was done at enrollment, 6 and 12 months. Flow cytometric analysis was performed for enumeration of counts and percentage of CD4⁺, CD8⁺, and CD19⁺ cells; expression of CD19, CD86, PD-1, CD3, CD8 and CD28 on lymphocytes was evaluated using whole blood staining technique with monoclonal antibodies. HIV-1 viral load was quantified using a real-time polymerase chain reaction. Serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin (IgM), and interleukin (IL)-7 were quantitated using quantitative enzyme-linked immunosorbent assay kits. The HIV-infected children were categorized into virological responders (VRs; HIV-1 plasma viral load <47 copies/mL) and virological nonresponders (VNRs; HIV-1 plasma viral load >1000 copies/mL) following 1-year cART. The frequency of CD28⁺ CTLs cells was higher (P < 0.0001), and the frequency of CD28-CTLs cells was lower (P < 0.0001) in VRs than VNRs. CD28⁺ and CD28-CTLs cells correlated with HIV-1 plasma viremia (r = -0.4695, P = 0.01; r = 0.40, P = 0.03, respectively). VRs had higher CD19 percentage (P = 0.04) and count (P = 0.01) than VNRs. CD19⁺ B cells in the VRs had lower expression of CD86 (P = 0.03) and PD-1 (P = 0.002) than VNRs. VR had lower levels of serum IgG (P = 0.03), IgM (P = 0.04), and IL-7 (P = 0.01) than VNRs. High baseline B-cell counts, lower serum IgG, IgM, IL-7 levels, lower activation and exhaustion of B cells, and higher frequency of CD28⁺ CTLs are associated with positive virological response, whereas elevated CD28-CTLs are associated with the poor virological outcomes in HIV-infected children.