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

• Published in: Journal of neurovirology Vol. 23; no. 2; pp. 216 - 225
• Main Authors: Vassallo, Matteo, Fabre, R., Durant, J., Lebrun-Frenay, C., Joly, H., Ticchioni, M., DeSalvador, F., Harvey-Langton, A., Dunais, B., Laffon, M., Cottalorda, J., Dellamonica, P., Pradier, C.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2017
• Subjects: Adult; AIDS Dementia Complex - diagnosis; AIDS Dementia Complex - immunology; AIDS Dementia Complex - pathology; AIDS Dementia Complex - virology; Antiretroviral Therapy, Highly Active; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Biomarkers - analysis; Biomedical and Life Sciences; Biomedicine; CD4 Lymphocyte Count; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - immunology; Cognitive Dysfunction - pathology; Cognitive Dysfunction - virology; Female; HIV - pathogenicity; HIV - physiology; Humans; Immunology; Infectious Diseases; Male; Middle Aged; Multivariate Analysis; Neurology; Neuropsychological Tests; Neurosciences; Permeability; Retrospective Studies; Risk Factors; Severity of Illness Index; Virology; Virus Replication; CPE score; Immune activation; CD4/CD8 ratio; HIV-associated neurocognitive disorders
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-016-0490-z

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.