| Publication Abstract Display |
| Type: Poster |
| Title: Older age is associated with higher antiretroviral
concentrations in cerebrospinal fluid in HIV-infected individuals. |
| Authors: Croteau D, Letendre S, Best B, Clifford D, Gelman B, Marra C, McArthur J, McCutchan JA, Simpson D, Grant I |
| Date: 03-05-2012 |
| Abstract:Background: Nearly 25% of HIV-infected individuals in the US are currently over age 50
and HIV prevalence rate in this age group is expected to double by 2015. Age-related
systemic and central nervous system (CNS) changes have the potential to result in
greater CNS exposure to antiretrovirals (ARVs), which has remained largely unexplored.
Methods: HIV-infected individuals were selected based on having had ARV
concentrations previously measured in blood plasma and cerebrospinal fluid (CSF) by
LC/MS/MS. The analysis targeted 3 drugs (tenofovir, efavirenz, and atazanavir), one
from each of the traditional ARV classes. Subjects with undetectable drug
concentrations in plasma were excluded. Univariable and multivariable methods,
including generalized additive models (GAM), were used to evaluate associations with
age. Neurocognitive functioning (NCF) was determined using standardized
comprehensive testing and summarized by the global deficit score. A decision tree
approach (CART) was used to explore non-linear relationships between ARV
concentrations and NCF. For each of the plasma and CSF drug concentrations, cut-offs
that achieved optimum NCF classifications were derived.
Results: 204 HIV-infected individuals (including 36 contributing samples for 2 ARV)
provided CSF (n=162) and plasma (n=230) specimens. Tenofovir CSF (n=44)
concentrations increased more steeply with age than plasma (n=44). Efavirenz
concentrations increased markedly in CSF (n=66) in subjects older than 55 with a less
steep and steadier increase with age for plasma (n=77) concentrations. Plasma (n=109)
atazanavir concentrations slightly declined with age while CSF (n=58) concentrations
remained stable, suggesting a relative increase in CSF with age based on CSF/plasma
ratio increase. Non-linear relationships between ARV CSF concentrations and NCF were
observed. CART analysis revealed that the group with intermediate ARV concentrations
had the best NCF.
Conclusions: The effect of aging on ARV exposure in the CNS varies by drug. In
general, older age was associated with greater ARV exposure in the CNS. Lower ARV
concentrations were associated with worse NCF, which may be due to suboptimal
virologic control. Higher ARV concentrations were also associated with worse NCF,
which may indicate drug neurotoxicity. More data in older HIV-infected individual are
needed to validate these findings. |