Effective combined antiretroviral therapy provides partial immune recovery to mycobacterial antigens in vertically infected, BCG-vaccinated youth living with HIV

Mariana Virginello Castelhano; Paulo César Martins Alves; Vítor Schandler Macedo; Mauro Pedromonico Arrym; Fernando Guimarães; Patricia Costa Panunto; Taís Nitsch Mazzola; Renan Marrichi Mauch; Maria Marluce Dos Santos Vilela; Marcos Tadeu Nolasco da Silva

doi:10.1016/j.tube.2022.102170

Effective combined antiretroviral therapy provides partial immune recovery to mycobacterial antigens in vertically infected, BCG-vaccinated youth living with HIV

Tuberculosis (Edinb). 2022 Mar:133:102170. doi: 10.1016/j.tube.2022.102170. Epub 2022 Jan 31.

Affiliations

¹ Center for Investigation in Pediatrics (CIPED), School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
² Center of Integral Services for Women's Health (CAISM), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
³ Laboratory of Pharmacology and Biochemistry, Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
⁴ Center for Investigation in Pediatrics (CIPED), School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil; Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
⁵ Center for Investigation in Pediatrics (CIPED), School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil; Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil. Electronic address: nolasco@unicamp.br.

PMID: 35131611
DOI: 10.1016/j.tube.2022.102170

Abstract

Background: We assessed the cytokine response by PBMC of youth living with HIV (YLHIV) under combined antiretroviral therapy (cART) to Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (BCG) antigens.

Methods: PBMC from 20 Brazilian YLHIV under cART with long-term (≥1 year) virological control, and 20 healthy controls were cultured for 24-96 h under stimulation with BCG, Mtb lysates, ESAT-6 and SEB. We measured TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10 and IL-17 in culture supernatants using a cytometric bead array.

Results: Controls had higher IFN-γ production at 24, 48, 72 and 96 h upon stimulation with BCG lysate, plateauing at 48 h (Median = 1991 vs. 733 pg/mL; p = 0.01), and after 48-72 h of stimulation with Mtb lysate, plateauing at 48 h (3838 vs. 2069 pg/mL; p = 0.049). YLHIV had higher TNF-α production at all time points upon stimulation with ESAT-6, with highest concentration at 36 h (388 vs. 145 pg/mL; p = 0.02). Within the YLHIV group, total CD4 T cell count and CD4/CD8 ratio were associated with IFN-γ response to Mtb lysate and ESAT-6, respectively.

Conclusions: Even under long-term cART, YLHIV seem to have a suboptimal T-helper-1 response to mycobacterial antigens. This can be explained by early immunodeficiency in vertical infection, with lasting damage.

Keywords: Antiretroviral therapy; BCG vaccine; Cytokine; HIV; Highly active; Mycobacterium tuberculosis; Young adult.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Antigens, Bacterial
BCG Vaccine / therapeutic use
HIV Infections* / complications
HIV Infections* / diagnosis
HIV Infections* / drug therapy
Humans
Leukocytes, Mononuclear
Mycobacterium tuberculosis*
Tuberculosis* / complications
Tuberculosis* / diagnosis
Tuberculosis* / drug therapy
Tumor Necrosis Factor-alpha

Substances

Antigens, Bacterial
BCG Vaccine
Tumor Necrosis Factor-alpha