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

Munhoz, Luiz Gustavo Cano; Spina, Fernanda Garcia; Machado, Daisy Maria; Gouvêa, Aída F.T.B.; Succi, Regina Célia de Menezes; Diaz, Ricardo Sobhie; Moraes-Pinto, Maria Isabel de

doi:10.1097/inf.0000000000002446

Cited by 7 publications

(15 citation statements)

References 25 publications

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“…Our results suggest that immune activation persists in YWVH, even among those on ART and virologically suppressed. These results contrast with previous results suggesting that treated and suppressed patients had a T‐cell activation and immune exhaustion profile similar to uninfected adolescents [ 31 ]. Distinct mention deserves results obtained for CD69 on T cells, considered the earliest activation marker during infections and increased levels have been associated with increased viral load [ 32 , 33 ].…”

Section: Discussioncontrasting

confidence: 99%

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

et al. 2021

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Introduction: Immune abnormalities have been described among youth with vertically acquired HIV (YWVH) despite antiretroviral treatment (ART). The CD4/CD8 ratio could be a useful prognostic marker. We assess immune activation and senescence in a cohort of YWVH in comparison to youth without vertically acquired HIV. Methods: YWVH under suppressive ART were included and compared to a group of HIV-negative donors (HD) matched by age and sex, from September 2019 to September 2020. Subset distribution and expression of activation, maturation, senescence and exhaustion markers on T and NK cells were studied on peripheral blood mononuclear cells by multiparametric flow cytometry. Results: Thirty-two YWVH (median age: 24.4 years (interquartile range: 22.5 to 28.3 years)) were included. Among YWVH, CD4-and CD8-T cells showed high levels of activation (HLA-DR/CD38), IL-7 receptor expression (CD127) and exhaustion (TIM-3). Regarding NK cells, YWVH showed increased levels of activation and exhaustion markers compared to HD. Strong inverted correlations were observed between T-cell activation (HLA-DR/CD38), senescence (CD57) and exhaustion (TIGIT, PD-1) levels with the CD4/CD8 ratio among YWVH. HLA-DR, CD69, NKG2D and NKG2A expression levels on NK cells also correlated with the CD4/CD8 ratio. Age at ART initiation was directly associated with higher frequency of CD16 high NK-cell subsets, exhaustion T-cell levels (CD57, TIM3) and NK cells activation levels. Conclusions: Immunological changes associated with vertically acquired HIV, characterized by increased activation and exhaustion levels in innate and adaptive immune components, are only partially restored by ART. The CD4/CD8 ratio can be a useful marker of disease progression for routine clinical practice.

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Section: Discussioncontrasting

confidence: 99%

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

et al. 2021

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“…By contrast, our study that was cited by Shen et al [1] showed that adolescents with detectable viral load had significantly lower IL-6 levels than controls, and those with an undetectable viral load had IL-6 levels comparable with controls [3].…”

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confidence: 84%

“…By contrast, evidence of immune exhaustion can be more readily observed in in-vitro T-cell stimulation experiments as some level of immune exhaustion is enough to interfere with the response to the intense stimulus applied in those assays. That is what we have performed in our study, so that adolescents with detectable viral load were the ones with the lowest cytokine levels [3]. The same approach was described by Underwood et al [5].…”

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confidence: 60%

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Cytokines in HIV infection: different methods of assessment require different interpretations

Munhoz

Moraes-Pinto

2022

Aids

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Cytokines in HIV infection: different methods of assessment require different interpretations We read with interest the article by Shen et al.[1] in a previous issue of AIDS. Studying bone turnover, the authors assessed interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in plasma from children living with HIV on different antiretroviral schemes and compared them with plasma levels from non-HIVinfected children.

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“…Figure2(A) The correlation between IFN-γ (n=40) and CD4 cells in HIV infected patients, with normal response to retroviral therapy, with CD4 decreasing rates less than 35 cell/microliter/year, or viral load lower than 20 copies/milliliter. (B) The correlation between sMICA (n=19) and CD4 cells in HIV infected patients with normal response to retroviral therapy, with CD4 decreasing rates less than 35 cell/microliter/year or viral load lower than 20 copies/milliliter [2][3][4][5][6][7][8]. …”

mentioning

confidence: 99%

Interferon Gamma and Soluble MICA as A New Biomarker for Immunological Severity Detection in HIV Infected Patients Undergoing Retroviral Therapy

Rareongjai

Pongtassanaham²,

Bhuddhisa

et al. 2021

J Health Sci Med Res

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Objective: Variations in immune responses to viral particles and antiretroviral drugs show interference of the cluster of differentiation number 4 T cell monitoring methods, leading to an inaccurate evaluation for human immunodeficiency virus infected patients receiving antiretroviral therapy. Other biological markers; such as cytokine; especially interferon gamma (IFN-γ) and soluble molecules of major histocompatibility complex class I chain related molecule A (sMICA), were designed as a novel severity marker.Material and Methods: Levels of IFN-γ and sMICA were evaluated for 69 patients, who presented with HIV infection; with no other diseases or inflammation. The candidates were classified into four groups, depending on their CD4 T cell count. The IFN-γ and sMICA serum content of the patients was detected in triplicate, using enzyme-linked immunosorbent assay.Results: Mean value of IFN-γ in each severity group was 49.1±9.7, 69.1±21.8, 63.0±12.8, and 69.4±18.4 picograms/ milliliter for none, mild, advanced, and severe cases, respectively. sMICA was detected at 36.8±19.6, 134.7±122.5, 33.6±12.4, and 83.9±40.0 international unit/milliliter, respectively. A significant association between IFN-γ and CD4 cells of normal anti-retroviral treatment response, defined by CD4 cells and viral loads, was observed using Spearman correlation, with p-values 0.033, r -0.434, 0.026 and -0.321, respectively. Conclusion: IFN-γ and sMICA were found to be associated with the CD4 count in the normal responses to antiretroviral treatment. This suggested that IFN-γ could be used as a biological marker for monitoring of immunological severity during anti-retroviral responses.

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

Cited by 7 publications

References 25 publications

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

Innate and adaptive abnormalities in youth with vertically acquired HIV through a multicentre cohort in Spain

Cytokines in HIV infection: different methods of assessment require different interpretations

Interferon Gamma and Soluble MICA as A New Biomarker for Immunological Severity Detection in HIV Infected Patients Undergoing Retroviral Therapy

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