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.
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.
Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France. m.vassallo@ch-cannes.fr.|Department of Internal Medicine, Cannes General Hospital, Cannes, France. m.vassallo@ch-cannes.fr.
Matteo
M
Vassallo
Department of Public Health, L'Archet Hospital, University of Nice, Nice, France.
R
R
Fabre
Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
J
J
Durant
Department of Neurology, Pasteur Hospital, University of Nice, Nice, France.
C
C
Lebrun-Frenay
Department of Neurology, Pasteur Hospital, University of Nice, Nice, France.
H
H
Joly
Immunology Laboratory Unit, L'Archet Hospital, University of Nice, Nice, France.
M
M
Ticchioni
Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
F
F
DeSalvador
Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
A
A
Harvey-Langton
Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.|Department of Public Health, L'Archet Hospital, University of Nice, Nice, France.
B
B
Dunais
Department of Neurology, Pasteur Hospital, University of Nice, Nice, France.
M
M
Laffon
Virology Laboratory Unit, L'Archet Hospital, University of Nice, Nice, France.
J
J
Cottalorda
Department of Infectious Diseases, L'Archet Hospital, University of Nice, Nice, France.
P
P
Dellamonica
Department of Public Health, L'Archet Hospital, University of Nice, Nice, France.
C
C
Pradier
D015526:AIDS Dementia Complex / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006678:HIV / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D010539:Permeability; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014779:Virus Replication
D000998:Antiviral Agents; D015415:Biomarkers
CD4/CD8 ratio; CPE score; HIV-associated neurocognitive disorders; Immune activation