Prolonged Antiretroviral Therapy in Adolescents With Vertical HIV Infection Leads to Different Cytokine Profiles Depending on Viremia Persistence

Author(s)

Cano Munhoz, Luiz Gustavo ^{[1, 2]} ; Spina, Fernanda Garcia ^[2] ; Machado, Daisy Maria ^[2] ; Gouvea, Aida ^[2] ; De Menezes Succi, Regina Celia ^[2] ; Diaz, Ricardo Sobhie ^[1] ; De Moraes-Pinto, Maria Isabel ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Div Infect Dis, Dept Med, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Div Pediat Infect Dis, Sao Paulo - Brazil

• Document type: Journal article
• Source: PEDIATRIC INFECTIOUS DISEASE JOURNAL; v. 38, n. 11, p. 1115-1120, NOV 2019.
• Web of Science Citations: 0

Abstract

Background: We investigated immune activation, exhaustion markers and cytokine expression upon stimulation in adolescents with vertical HIV infection. Methods: Thirty adolescents receiving antiretroviral therapy (ART) for vertical HIV infection, including 12 with detectable viral load (HIV/DET), 18 with undetectable viral load (HIV/UND) and 30 control adolescents without HIV infection (CONTROL), were evaluated for immune activation and programmed cell death protein-1 expression by flow cytometry, and 21 cytokines by Luminex Multiple Analyte Profiling technology after in vitro peripheral blood phytohemagglutinin stimulation. Results: Lower CD4(+) T cells and higher T cell activation and exhaustion markers were noted on CD4(+) T and on CD8(+) T cells and memory subsets from HIV/DET group, who also produced lower in vitro IFN-gamma, IL-10, IL-13, IL-17A, IL-5 and IL-6 than HIV/UND group. HIV/UND were comparable with CONTROL group in respect to CD4(+) T cell counts and T cell activation and exhaustion markers, but with higher in vitro production of ITAC (a chemokine with leukocyte recruitment function), IL-4 and IL-23. An inverse correlation between cytokine production and programmed cell death protein-1 expression on CD4(+) T and CD8(+) T subsets was detected. Conclusions: Persistent viremia despite ART leads to T cell activation and immune exhaustion with low cytokine production, whereas viral suppression by ART leads to parameters similar to CONTROL, although a different cytokine profile is observed, indicating residual HIV impact despite absence of detectable viremia. (AU)

• FAPESP's process: 13/21853-1 - Tolerability, immunogenicity and persistence of immune response to tetanus, diphtheria and pertussis (Tdap) vaccine in adolescents infected by the Human Immunodeficiency Virus (HIV)
• Grantee: Maria Isabel de Moraes Pinto
• Support Opportunities: Regular Research Grants