Background:  Antiretrovirals have poor penetration into the CNS, leading to speculation that virus may become sequestered in the CNS,increasing the propensity for neurological disease.  It is not known whether regimens with higher CNS penetration may provide more protection from neurological disease.

Methods:  Data from 45 subjects prospectively enrolled in a study of the cognitive effects of HAART and who were failing their current antiretroviral regimen (> 1000 cps/ml HIV RNA) were analyzed.  Subjects placed on regimens with at least one CNS penetrating (ZDV, IDV, ABC, 3TC, EFV, NVP, D4T) antiretroviral were compared to those with non-penetrating regimens using mixed model analysis of variance controlling for baseline values of HIV RNA, neurological functioning, and number of antiretrovirals.  Subjects were administered a standardized neurological evaluation and neuropsychological battery prior to antiretroviral start, and 29 subjects had follow-up of at least 6 months. 

Results:  There was significant improvement at follow-up in neurological functioning (F(1,25)=4.05, p = 0.05), plasma HIV RNA (F(1,23)=8.24, p <0.005), with a trend for CSF HIV RNA to decrease (p <0.20).  No significant (interaction) differences were found between 10 subjects with CNS penetrating regimens at follow-up compared to those 19 subjects on non - penetrating regimens on the neurological examination (F(1,25)=1.42, p = ns) and neuropsychological examination (F(1,25)= 1.73, p = ns).  

Conclusions:  In subjects with virological failure on current treatment, regimens containing a CNS penetrating antiretroviral appear not to have a superior neuroprotective effect over suppression of HIV RNA.  In this study, we found that effective virological suppression appeared to be more important than whether or not the regimen contained a CNS penetrating antiretroviral.

Keywords: CNS; Antiretroviral; Neurology