Survival after neuroAIDS: association with antiretroviral CNS Penetration-Effectiveness score.
OBJECTIVE
We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis.


METHODS
Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models.


RESULTS
In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52).


CONCLUSIONS
At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.
INSERM U943, 56 Bd V. Auriol, Paris Cedex 13, France. elanoy@ccde.chups.jussieu.fr
E
E
Lanoy
M
M
Guiguet
M
M
Bentata
E
E
Rouveix
C
C
Dhiver
I
I
Poizot-Martin
D
D
Costagliola
J
J
Gasnault
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008581:Meningitis / Q000188:drug therapy / Q000401:mortality; D008875:Middle Aged; D009460:Neurologic Examination; D016781:Toxoplasmosis, Cerebral / Q000188:drug therapy / Q000401:mortality; D055815:Young Adult
D044966:Anti-Retroviral Agents