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.

Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.