Can high central nervous system penetrating antiretroviral regimens protect against the onset of HIV-associated neurocognitive disorders?
OBJECTIVE
To assess changes over time in neuropsychological test results (NPr) and risk factors among a regularly followed HIV-infected patient population.


METHODS
Prospective cohort of HIV-infected patients randomly selected to undergo neuropsychological follow-up. Test score was adjusted for age, sex and education. Patients were divided into five groups: normal tests, neuropsychological deficit (one impaired cognitive domain), asymptomatic neurocognitive disorders (ANIs), mild neurocognitive disorders (MNDs) and HIV-associated dementia (HAD). Demographic and background parameters including CSF drug concentration penetration effectiveness (CPE) score 2010 were recorded. Changes in NPr and associated risk factors were analyzed.


RESULTS
Two hundred and fifty-six patients underwent neuropsychological tests and 96 accepted follow-up approximately 2 years later. The groups were comparable. Upon neuropsychological retesting, six patients improved, 31 worsened and 59 were stable. The proportion of patients with HIV-associated neurocognitive disorders (HANDs) rose from 26 to 45%, with ANIs and MNDs still mostly represented. Most patients initially diagnosed with HANDs remained stable, five of 25 showed clinical improvement and three of 25 deteriorated. Of 33 patients with normal tests, four deteriorated, whereas 24 of 38 with initial neuropsychological deficit had poorer NPr, and contributed most of the new HAND cases. Patients with clinical deterioration had a lower CPE score both at inclusion (6.9 vs. 8.1; P = 0.005) and at the end of follow-up (7.2 vs. 7.8; P = 0.08) than those with improved or stable performance. This was confirmed by multivariate analysis.


CONCLUSIONS
Patients with higher CPE scores upon inclusion and at the end of follow-up were at lower risk of clinical worsening, suggesting that combination antiretroviral therapy with better CSF penetration could protect against cognitive deterioration.
aDepartment of Infectious Diseases, L'Archet Hospital, University of Nice bDepartment of Internal Medicine, Cannes General Hospital cDepartment of Neurology, Pasteur Hospital dDepartment of Public Health, L'Archet Hospital eVirology Laboratory Unit, L'Archet Hospital fImmunology Laboratory Unit, L'Archet Hospital, University of Nice, France.
Matteo
M
Vassallo
Jacques
J
Durant
Virginie
V
Biscay
Christine
C
Lebrun-Frenay
Brigitte
B
Dunais
Muriel
M
Laffon
Alexandra
A
Harvey-Langton
Jacqueline
J
Cottalorda
Michel
M
Ticchioni
Helene
H
Carsenti
Christian
C
Pradier
Pierre
P
Dellamonica
D015526:AIDS Dementia Complex / Q000453:epidemiology* / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D055815:Young Adult
D044966:Anti-Retroviral Agents