HIV-associated lymphoma in the era of combination antiretroviral therapy: shifting the immunological landscape

Carroll, Virginia; Garzino-Demo, Alfredo

doi:10.1093/femspd/ftv044

Cited by 28 publications

(21 citation statements)

References 74 publications

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“…Effective NK cell cytolytic function requires delicate balance between the activating and inhibitory receptors [ 8 ]. Downregulation of the receptors during chronic HIV infection has been associated with risk of development non-AIDS-defining cancers [ 28 , 29 ]. Low NKp46 receptor expression was previously reported after three years of HIV treatment in a European cohort, where it improved with increasing duration of ART [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

Nabatanzi

Bayigga

Cose

et al. 2019

Clinical Immunology

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Background We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/μl) and age-matched healthy-HIV-uninfected individuals from the same community. Methods Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56 +/- CD16 +/− ). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production. Results CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals. Conclusion NK cell activation and dysfunction persisted despite seven years of suppressive ART with “normalization” of peripheral CD4 counts.

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Section: Discussionmentioning

confidence: 99%

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

Nabatanzi

Bayigga

Cose

et al. 2019

Clinical Immunology

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“…Even though HL is not an AIDS-defining illness, the incidence of cHL is 10-fold higher than in the general population, and essentially all of that increase involves EBV-positive tumours of mixed cellularity or lymphocyte-depleted subtypes [ 60 ]. Just as with BL, the development of HIV-related HL is not dependent on profound T cell impairment; indeed cHL incidence among HIV carriers has slightly increased after the introduction of HAART [ 16 ]. Interestingly these tumours tend to arise somewhat later than HIV-related BL, in patients with relatively modest reductions in CD4 + T cell counts.…”

Section: Hodgkin Lymphomamentioning

confidence: 99%

Epstein–Barr virus-associated lymphomas

Shannon-Lowe

Rickinson

Bell

2017

Phil. Trans. R. Soc. B

354

305

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Epstein–Barr virus (EBV), originally discovered through its association with Burkitt lymphoma, is now aetiologically linked to a remarkably wide range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. Some occur as rare accidents of virus persistence in the B lymphoid system, while others arise as a result of viral entry into unnatural target cells. The early finding that EBV is a potent B-cell growth transforming agent hinted at a simple oncogenic mechanism by which this virus could promote lymphomagenesis. In reality, the pathogenesis of EBV-associated lymphomas involves a complex interplay between different patterns of viral gene expression and cellular genetic changes. Here we review recent developments in our understanding of EBV-associated lymphomagenesis in both the immunocompetent and immunocompromised host.This article is part of the themed issue ‘Human oncogenic viruses’.

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“…Previous studies have shown that the combination of cART with chemotherapy increased overall survival of these patients [ 3 – 5 ]. However, even in well-treated HIV-positive patients, the results of lymphoma treatment are, although improving, still not as good as in HIV-negative patients [ 6 – 8 ]. Apart from the HIV infection itself, drug–drug interactions between cART and cytostatics may play an important role in the treatment outcome of patients.…”

Section: Introductionmentioning

confidence: 99%

Outcome effects of antiretroviral drug combinations in HIV-positive patients with chemotherapy for lymphoma: a retrospective analysis

et al. 2018

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Background The combination of combined active antiretroviral therapy (cART) with chemotherapy in the treatment of lymphoma in human immunodeficiency virus (HIV)-positive patients has improved the overall survival of these patients. However, drug–drug interactions between antineoplastic agents and the antiretroviral agents non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) can occur by influencing the activity of the CYP3A4 enzyme. So far, little is known about the clinical relevance of this interaction: the effect on the efficacy and toxicity of the chemotherapy. Also, there is no general consensus which cART is preferable in combination with antineoplastic drugs. Objective To compare PI-based with NNRTI-based cART on the efficacy and toxicity of chemotherapy in lymphoma patients. Setting The Onze Lieve Vrouwe Gasthuis, located in Amsterdam, The Netherlands. Method A retrospective observational cohort study including all patients with HIV and lymphoma over a 10-year period. Clinical outcome (response to chemotherapy and survival) and toxicity of chemotherapy (renal, hepatic and bone marrow toxicity as well as dose reduction, treatment delay and discontinuation) was compared in patients with PI based and NNRTI-based cART. Main outcome measure: Response to chemotherapy and survival. Results Patients using PI-based cART (n = 22) had a significantly lower 1 year survival compared to NNRTI-based cART (n = 21). No significant differences were observed in reaching complete remission after chemotherapy. No overall significant differences in toxicity and discontinuation of the chemotherapy were observed. However, there was a trend towards more severe bone-marrow toxicity in patients with PI-based cART. In addition, patients with PI-based cART received earlier dose-reduction and treatment delay, indicating increased toxicity in PI-treated patients. Conclusion This retrospective study shows that PI-based cART is inferior in combination with chemotherapy to NNRTI-based cART: a lower 1 year survival is observed and dose-reduction and treatment delay occur earlier, possibly based on an earlier onset of toxicity.

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HIV-associated lymphoma in the era of combination antiretroviral therapy: shifting the immunological landscape

Cited by 28 publications

References 74 publications

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort

Epstein–Barr virus-associated lymphomas

Outcome effects of antiretroviral drug combinations in HIV-positive patients with chemotherapy for lymphoma: a retrospective analysis

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