Correlating <scp>HIV</scp> tropism with immunological response under combination antiretroviral therapy

Bader, Joëlle; Schöni‐Affolter, Franziska; Böni, Jürg; Gorgievski-Hrisoho, Meri; Martinetti, Gladys; Battegay, Manuel; Klimkait, Thomas

doi:10.1111/hiv.12365

Cited by 11 publications

(10 citation statements)

References 27 publications

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“…Our hypothesis is in line with a study demonstrating that selection of X4-tropic viruses before initiation of antiretroviral therapy was associated with only partial immune recovery during treatment 31 . A possible confounder in this study was the generally lower baseline CD4 count in the immunological non-responder group.…”

Section: Discussionsupporting

confidence: 90%

“…To explore correlations between host immunological markers and X4-tropism, we measured an array of markers and performed a GTT in 100 South African HIV-1 C infected ART-naive patients who enrolled in a cross-sectional study. The median age of all enrolled participants was 37 years [interquartile range (IQR): [31][32][33][34][35][36][37][38][39][40], they had a median CD4 + T-lymphocyte count (CD4 count) of 215 cells/µL (IQR: 54-412) and 61% were female (61/100) ( Table 1). HIV-1 was predicted to be X4-tropic in 24% of participants using a False-Positive Rate (FPR) of ≤ 3.5% (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…A possible confounder in this study was the generally lower baseline CD4 count in the immunological non-responder group. However, some patients with low CD4 counts (< 150 cells/µl) belonged to the immune responders, whereas others with a baseline count of > 150 cells/µl had a CD4 increase < 400 cells 31 . In the HIV-1C cohort, there was a strong association between lower CD4 count and X4-tropism at the time of tropism determination.…”

Section: Discussionmentioning

confidence: 98%

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Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection

Connell

Hermans

Wensing

et al. 2020

Sci Rep

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HIV-1 cell entry is mediated by binding to the CD4-receptor and chemokine co-receptors CCR5 (R5) or CXCR4 (X4). R5-tropic viruses are predominantly detected during early infection. A switch to X4-tropism often occurs during the course of infection. X4-tropism switching is strongly associated with accelerated disease progression and jeopardizes CCR5-based HIV-1 cure strategies. It is unclear whether host immunological factors play a causative role in tropism switching. We investigated the relationship between immunological factors and X4-tropism in a cross-sectional study in HIV-1 subtype C (HIV-1C)-infected patients and in a longitudinal HIV-1 subtype B (HIV-1B) seroconverter cohort. Principal component analysis identified a cluster of immunological markers (%HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD8+ T-cells, %CD70+ CD4+ T-cells, %CD169+ monocytes, and absolute CD4+ T-cell count) in HIV-1C patients that was independently associated with X4-tropism (aOR 1.044, 95% CI 1.003–1.087, p = 0.0392). Analysis of individual cluster contributors revealed strong correlations of two markers of T-cell activation (%HLA-DR+ CD4+ T-cells, %HLA-DR+CD38+ CD4+ T-cells) with X4-tropism, both in HIV-1C patients (p = 0.01;p = 0.03) and HIV-1B patients (p = 0.0003;p = 0.0001). Follow-up data from HIV-1B patients subsequently revealed that T-cell activation precedes and independently predicts X4-tropism switching (aHR 1.186, 95% CI 1.065–1.321, p = 0.002), providing novel insights into HIV-1 pathogenesis and CCR5-based curative strategies.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

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Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection

Connell

Hermans

Wensing

et al. 2020

Sci Rep

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“…Increase in the CD4 + T-cell count > 400 cells/µl from baseline at 5 years after ART initiation, with an undetectable plasma VL. 117 Total CD4 + T-cell count < 350 cells/µl at 2 years after ART initiation, with an undetectable plasma VL Total CD4 + T-cell count > 500 cells/µl at 2 years after ART initiation, with an undetectable plasma VL. 66,116,175,244 Total CD4 + T-cell count < 400 cells/µl at 2 years after ART initiation, with plasma HIV RNA < 20 copies/ml.…”

Section: Definition Of "Immunological Nonresponder" Definition Of "Immentioning

confidence: 99%

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Yang

Zhang

et al. 2020

Journal of Leukocyte Biology

190

214

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The morbidity and mortality of HIV type‐1 (HIV‐1)‐related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV‐1 replication and gradual recovery of CD4+ T‐cell counts. However, ∼10–40% of HIV‐1‐infected individuals fail to achieve normalization of CD4+ T‐cell counts despite persistent virological suppression. These patients are referred to as “inadequate immunological responders,” “immunodiscordant responders,” or “immunological non‐responders (INRs)” who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non‐AIDS events and present higher rates of mortality than HIV‐1‐infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV‐1‐infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.

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“…Bader et al investigated the hypothesis that tropism determination can be used as a parameter for disease progression. They found that 60% (9 out of 15) of patients with X4‐tropic viruses and 46.4% (32 out of 69) with R5‐tropic viruses were in the incomplete responder group ( P = 0.339), whose CD4 count remained <400 cells/μL after 5 years on current antiretroviral therapy.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of C‐C chemokine receptor type 5 tropism among human immunodeficiency virus 1–infected patients in South Korea

Song

Ahn

Kim

et al. 2018

Journal of Medical Virology

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Correlating HIV tropism with immunological response under combination antiretroviral therapy

Cited by 11 publications

References 27 publications

Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection

Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

Prevalence of C‐C chemokine receptor type 5 tropism among human immunodeficiency virus 1–infected patients in South Korea

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