Cytomegalovirus-specific CD4+ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV

Vibe Ballegaard; Karin Kaereby Pedersen; Maria Pedersen; Peter Brændstrup; Nikolai Kirkby; Anette Stryhn Buus; Lars P. Ryder; Jan Gerstoft; Susanne Dam Nielsen

doi:10.1097/QAI.0000000000001753

Cytomegalovirus-specific CD4⁺ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV

Vibe Ballegaard, Karin Kaereby Pedersen, Maria Pedersen, Peter Brændstrup, Nikolai Kirkby, Anette Stryhn Buus, Lars P. Ryder, Jan Gerstoft, Susanne Dam Nielsen^*

^*Corresponding author for this work

Abstract

Background: Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable combination antiretroviral therapy (cART) remain unknown. We investigated the association between immunity against cytomegalovirus (CMV), HIV-specific variables, and NCI in PLWHIV on stable cART and with low comorbidity. Methods: Fifty-two PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, sex, education, and comorbidity were tested with a neurocognitive test battery, and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4 + and CD8 + T-cell responses were measured using intracellular cytokine staining and flow cytometry. NCI was defined as a global deficit scale score (GDS score) ≥0.5. GDS scores and domain-specific scores defined severity of NCI. Logistic and linear multivariable regression analyses were used. Results: NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 [95% confidence interval (CI): 1.15 to 23.41, P = 0.033] for NCI. In PLWHIV, higher CMV-specific CD4 + T-cell responses increased the probability of NCI with an aOR of 1.68 (95% CI: 1.10 to 2.57) for CMV-pp65 or an aOR of 3.73 (95% CI: 1.61 to 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8 + T cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/mL) was associated with worse GDS scores (β = 0.08) (0.01-0.16), P = 0.044), specifically in the domain of speed of information processing (β = 0.20 (0.04-0.36, P = 0.019). Conclusions: PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4⁺ T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of immunity against CMV on risk of NCI are warranted.

Original language	English
Journal	Journal of Acquired Immune Deficiency Syndromes
Volume	79
Issue number	1
Pages (from-to)	117-125
Number of pages	9
ISSN	1525-4135
DOIs	https://doi.org/10.1097/QAI.0000000000001753
Publication status	Published - 2018

Keywords

CMV-IgG
CMV-specific T cells
cytomegalovirus
HIV
HIV-associated neurocognitive disorders
neurocognitive impairment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/QAI.0000000000001753

Cite this

Ballegaard, V., Pedersen, K. K., Pedersen, M., Brændstrup, P., Kirkby, N., Buus, A. S., Ryder, L. P., Gerstoft, J., & Nielsen, S. D. (2018). Cytomegalovirus-specific CD4⁺ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV. Journal of Acquired Immune Deficiency Syndromes, 79(1), 117-125. https://doi.org/10.1097/QAI.0000000000001753

Cytomegalovirus-specific CD4⁺ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV. / Ballegaard, Vibe; Pedersen, Karin Kaereby; Pedersen, Maria et al.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 79, No. 1, 2018, p. 117-125.

Research output: Contribution to journal › Journal article › Research › peer-review

Ballegaard, V, Pedersen, KK, Pedersen, M, Brændstrup, P, Kirkby, N, Buus, AS, Ryder, LP, Gerstoft, J & Nielsen, SD 2018, 'Cytomegalovirus-specific CD4⁺ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV', Journal of Acquired Immune Deficiency Syndromes, vol. 79, no. 1, pp. 117-125. https://doi.org/10.1097/QAI.0000000000001753

@article{69d516763887447f839cb7c7ba51ae3d,

title = "Cytomegalovirus-specific CD4+ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV",

abstract = "Background: Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable combination antiretroviral therapy (cART) remain unknown. We investigated the association between immunity against cytomegalovirus (CMV), HIV-specific variables, and NCI in PLWHIV on stable cART and with low comorbidity. Methods: Fifty-two PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, sex, education, and comorbidity were tested with a neurocognitive test battery, and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4 + and CD8 + T-cell responses were measured using intracellular cytokine staining and flow cytometry. NCI was defined as a global deficit scale score (GDS score) ≥0.5. GDS scores and domain-specific scores defined severity of NCI. Logistic and linear multivariable regression analyses were used. Results: NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 [95% confidence interval (CI): 1.15 to 23.41, P = 0.033] for NCI. In PLWHIV, higher CMV-specific CD4 + T-cell responses increased the probability of NCI with an aOR of 1.68 (95% CI: 1.10 to 2.57) for CMV-pp65 or an aOR of 3.73 (95% CI: 1.61 to 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8 + T cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/mL) was associated with worse GDS scores (β = 0.08) (0.01-0.16), P = 0.044), specifically in the domain of speed of information processing (β = 0.20 (0.04-0.36, P = 0.019). Conclusions: PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4+ T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of immunity against CMV on risk of NCI are warranted.",

keywords = "CMV-IgG, CMV-specific T cells, cytomegalovirus, HIV, HIV-associated neurocognitive disorders, neurocognitive impairment",

author = "Vibe Ballegaard and Pedersen, {Karin Kaereby} and Maria Pedersen and Peter Br{\ae}ndstrup and Nikolai Kirkby and Buus, {Anette Stryhn} and Ryder, {Lars P.} and Jan Gerstoft and Nielsen, {Susanne Dam}",

year = "2018",

doi = "10.1097/QAI.0000000000001753",

language = "English",

volume = "79",

pages = "117--125",

journal = "J A I D S",

issn = "1525-4135",

publisher = "Lippincott Williams & Wilkins",

number = "1",

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TY - JOUR

T1 - Cytomegalovirus-specific CD4+ T-cell responses and CMV-IgG levels are associated with neurocognitive impairment in people living with HIV

AU - Ballegaard, Vibe

AU - Pedersen, Karin Kaereby

AU - Pedersen, Maria

AU - Brændstrup, Peter

AU - Kirkby, Nikolai

AU - Buus, Anette Stryhn

AU - Ryder, Lars P.

AU - Gerstoft, Jan

AU - Nielsen, Susanne Dam

PY - 2018

Y1 - 2018

N2 - Background: Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable combination antiretroviral therapy (cART) remain unknown. We investigated the association between immunity against cytomegalovirus (CMV), HIV-specific variables, and NCI in PLWHIV on stable cART and with low comorbidity. Methods: Fifty-two PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, sex, education, and comorbidity were tested with a neurocognitive test battery, and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4 + and CD8 + T-cell responses were measured using intracellular cytokine staining and flow cytometry. NCI was defined as a global deficit scale score (GDS score) ≥0.5. GDS scores and domain-specific scores defined severity of NCI. Logistic and linear multivariable regression analyses were used. Results: NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 [95% confidence interval (CI): 1.15 to 23.41, P = 0.033] for NCI. In PLWHIV, higher CMV-specific CD4 + T-cell responses increased the probability of NCI with an aOR of 1.68 (95% CI: 1.10 to 2.57) for CMV-pp65 or an aOR of 3.73 (95% CI: 1.61 to 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8 + T cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/mL) was associated with worse GDS scores (β = 0.08) (0.01-0.16), P = 0.044), specifically in the domain of speed of information processing (β = 0.20 (0.04-0.36, P = 0.019). Conclusions: PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4+ T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of immunity against CMV on risk of NCI are warranted.

AB - Background: Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable combination antiretroviral therapy (cART) remain unknown. We investigated the association between immunity against cytomegalovirus (CMV), HIV-specific variables, and NCI in PLWHIV on stable cART and with low comorbidity. Methods: Fifty-two PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, sex, education, and comorbidity were tested with a neurocognitive test battery, and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4 + and CD8 + T-cell responses were measured using intracellular cytokine staining and flow cytometry. NCI was defined as a global deficit scale score (GDS score) ≥0.5. GDS scores and domain-specific scores defined severity of NCI. Logistic and linear multivariable regression analyses were used. Results: NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 [95% confidence interval (CI): 1.15 to 23.41, P = 0.033] for NCI. In PLWHIV, higher CMV-specific CD4 + T-cell responses increased the probability of NCI with an aOR of 1.68 (95% CI: 1.10 to 2.57) for CMV-pp65 or an aOR of 3.73 (95% CI: 1.61 to 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8 + T cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/mL) was associated with worse GDS scores (β = 0.08) (0.01-0.16), P = 0.044), specifically in the domain of speed of information processing (β = 0.20 (0.04-0.36, P = 0.019). Conclusions: PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4+ T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of immunity against CMV on risk of NCI are warranted.

KW - CMV-IgG

KW - CMV-specific T cells

KW - cytomegalovirus

KW - HIV

KW - HIV-associated neurocognitive disorders

KW - neurocognitive impairment

U2 - 10.1097/QAI.0000000000001753

DO - 10.1097/QAI.0000000000001753

M3 - Journal article

C2 - 29781883

AN - SCOPUS:85059160404

SN - 1525-4135

VL - 79

SP - 117

EP - 125

JO - J A I D S

JF - J A I D S

IS - 1

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