696 HAART Improves Neurological Functioning K. Robertson*, W. Robertson, S. Fiscus, M. Beam, C. Hall Univ of North Carolina, Chapel Hill
Background: While the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients (pts) with HIV infection, concerns remain that these medications, which cross the blood brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be progressive long-term neurological decline in pts with adequate systemic response.
Objective: To evaluate the effects of systemically effective HAART on nervous system function over time.
Methods: In a prospective longitudinal study, we are evaluating subjects with detailed neurological, psychological, and neuro-psychological examination before the institution of HAART and at set intervals while on stable HAART therapy. At each evaluation, subjects also undergo ultra sensitive HIV RNA quantitative evaluation in both plasma and cerebrospinal fluid (CSF).
Results: Fifty (50) subjects have been evaluated at baseline before treatment with HAART or after failing 1 treatment regimen and before instituting a different HAART regimen. Twenty-nine (29) subjects have undergone a 6-month follow-up on stable HAART. Both plasma and CSF viral burden have declined after treatment, (F[2,26] = 436.9, p < 0.0001; pre 4.85 [0.17], HAART 3.11 [0.22]) and CSF (F[2,20] = 152.9, p < 0.0001; pre 2.92 [0.17], HAART 1.69 [0.22]). A quantitative scoring procedure was utilized for the neurological exam, and summary z-scores were calculated for the neuropsychological battery. Using a mixed model, significant improvements were found after treatment in neurological scores (F[2,28] = 30.14, p < 0.001; pre 50.9 [6.7], HAART 32.9 [8.6]) and neuropsychological scores (F[2,28] = 46.23, p < 0.0001; pre 1.01 [0.11], HAART -0.95 [0.13]).
Conclusions: In the current prospective study, we have found significant improvement in neurological and neuropsychological functioning following treatment with HAART. These improvements in functioning occurred in the context of significant decreases in plasma and CSF viral load. These results indicate that despite the poor CNS penetration of these agents, there is a satisfactory short-term improvement in both CNS viral burden and nervous system function with HAART therapy. However, as treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.
