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Association between CSF and peripheral markers of immune-

activation/inflammation and elevated intratechal HIV–RNA levels in a cohort

of HIV-infected antiretroviral naïve individuals

Esther Merlini, PhD

Clinic of Infectious Diseases

Department of Health Sciences

University of Milan

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150 HIV+ cART naive pts

Lumbar puncture and blood sampling

for HIV-RNA quantification and

Immune phenotypes

92/150pts

neurocognitive screening tests

64/92 pts

CSF/plasma inflammation

marker measurements

Objective:To investigate the possible associations between high CSF HIV-RNA and CSF and peripheral blood inflammatory biomarkers in a cohort

of antiretroviral-naïve HIV-positive patients (pts)

Study Design:

3%

97%

Viral Escape (VE) CSF VL>1Log plasma VL

VE positive VE negative32%

68%

HIV+ cART naive pts

H-CSF: HIV-RNA>10.000 cp/mlL-CSF: HIV-RNA<10.000 cp/ml

Results:

No differences in neurocognitive screening test (MMSE, IHDS, FAB) performance between H-CSF and L-CSF (37% vs 40%)

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Univariate Logistic Regression OR 95% CI P value

Plasma Log10 HIV-RNA(each Log10 UI/mL more) 2.09 1.33-3.29 0.001

Current CD4+ T cells(each cells/mmc more) 0.998 0.996-1 0.051

Nadir CD4+ T cells(each cells/mmc more) 0.998 0.996-1 0.083

CD4/CD8 ratio(each unit more) 0.121 0.018-0.801 0.029

CD8+CD38+ %(each unit more) 1.028 0.997-1.059 0.08

CD8+CD38+CD45R0+ %(each unit more) 1.051 1.011-1.093 0.012

CD4+CD127+ %(each unit more) 0.933 0.876-0.995 0.034

CD8+CD45R0+ %(each unit more) 1.031 0.996-1.068 0.081

CD4+CD45RA+ %(each unit more) 0.947 0.871-1.03 0.201

CD8+CD45RA+ %(each unit more) 0.937 0.885-0.992 0.026

Multivariate Logistic

Regression

AOR* 95% CI P value

Plasma Log10 HIV-RNA(each Log10 UI/mL more)

1.695 0.992-2.895 0.054

CD4/CD8 ratio(each unit more)

0.039 0.001-2.771 0.136

CD4+CD127+ %(each unit more)

1.066 0.921-1.235 0.392

CD8+CD45RA+ %(each unit more)

0.934 0.877-0.995 0.035

CD8+CD38+ %(each unit more)

0.995 0.95-1.042 0.832

Factors associated to high CSF HIV RNA- Multivariate Logistic Regression

Factors associated with high CSF HIV RNA- Univariate Logistic Regression

*Mutually adjusted

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CSF pro-inflammatory cytokine/chemokines

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Conclusions• In our cohort of HIV+ cART naïve patients, we failed to

observe any impairment in first line neurocognitive assessment in individuals with high viral replication in the CNS compartment

• Pts displaying high CSF VL are characterized by lower naïve CD8+ T-cell compartment and higher peripheral and central immune-activation, suggesting an exhaustion of peripheral immune system, likely related to ongoing chronic replicative infection

• Further research should better assess the significance of pre-therapy high CSF viral replication on clinical and immunological reconstitution on cART

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Acknowledgements

University of Milan

Dept of Health Sciences

University of Torino

Dept of Medical Sciences

• Francesca Iannuzzi• Francesca Bai• Mattia Trunfio• Antonella d’Arminio Monforte• Giulia Marchetti

• Stefano Bonora• Andrea Calcagno