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A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication

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Abstract

Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

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Acknowledgments

We wish to thank the patients who accepted to take part in the Neuradapt study and Monique Massard, Valerie Martinez, Ghislaine Valentini, Francoise Alexis, and Suzanne Raynaud who collected blood samples. We give thanks also to the laboratory technicians of the Immunology and Virology Units, in particular to Rachid Mamhoud. We also wish to thank Patrizia Comi.

Large amounts of this work have been previously presented at the 23rd Conference on Retroviruses and Opportunistic Infections (CROI) in Boston 2016 (Vassallo et al. 2016).

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Authors and Affiliations

  1. Department of Infectious Diseases, L’Archet Hospital, University of Nice, Nice, France

    Matteo Vassallo, J. Durant, F. DeSalvador, A. Harvey-Langton, B. Dunais & P. Dellamonica

  2. Department of Internal Medicine, Cannes General Hospital, Cannes, France

    Matteo Vassallo

  3. Department of Public Health, L’Archet Hospital, University of Nice, Nice, France

    R. Fabre, B. Dunais & C. Pradier

  4. Department of Neurology, Pasteur Hospital, University of Nice, Nice, France

    C. Lebrun-Frenay, H. Joly & M. Laffon

  5. Immunology Laboratory Unit, L’Archet Hospital, University of Nice, Nice, France

    M. Ticchioni

  6. Virology Laboratory Unit, L’Archet Hospital, University of Nice, Nice, France

    J. Cottalorda

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  1. Matteo Vassallo
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  2. R. Fabre
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  3. J. Durant
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  11. J. Cottalorda
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  13. C. Pradier
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Correspondence to Matteo Vassallo.

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The study was approved by the Montpellier Ethics Committee and patients signed informed consent.

Study funding

This study received funding from Abbott, Glaxo-Smith-Kline, Boehringer, Gilead, Tibotec, and Merck companies. The pharmaceutical companies mentioned above did not participate in the design or the conduct of the study; in the collection, management, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript. All the phases of the work described above were prepared independently by the authors.

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The authors declare that they have no conflict of interest.

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Vassallo, M., Fabre, R., Durant, J. et al. A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication. J. Neurovirol. 23, 216–225 (2017). https://doi.org/10.1007/s13365-016-0490-z

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