Session 18Oral Abstract Presentations Viral Neuropathogenesis Session Day and Time: Wednesday 10 am - 12:30 pm Presentation Time: 11:00 Room: Ballroom C
90 Clearance of HIV-1 RNA from Cerebrospinal Fluid is Most Rapid during the First Three Days of Antiretroviral Therapy in Asymptomatic Patients D. W. Haas*, B. Johnson, T. Hulgan, J. Nicotera, P. Spearman Vanderbilt Univ Sch of Med, Nashville, TN
Background: Seminal studies of kinetics of plasma HIV-1 RNA decay during initiation of antiretroviral therapy (ART) have helped define viral dynamics of HIV replication. More recent data suggests that drug potency can be predicted by quantifying maximal plasma HIV-1 RNA decay rates during the initial days of ART. We previously described discordant HIV-1 RNA decay in CSF versus plasma during initiation of ART, suggesting that HIV-1 RNA in CSF arises at least in part from a source other than plasma. The present analyses were performed to determine the time of most rapid HIV-1 RNA decay in CSF during initiation of ART in asymptomatic, treatment-naive adults.
Methods: During our previous ultra-intensive CSF sampling study involving 4 subjects, lumbar CSF was collected continuously via an indwelling catheter at baseline (17 assays at 3-hr intervals), and again on day 4-5 following initiation of 3-drug ART with d4T, 3TC, and nelfinavir (17 assays at 3-hr intervals). CSF HIV-1 RNA was quantified by NASBA. That data is the basis for the present kinetic analyses. For each subject, rate of HIV-1 RNA decay in CSF during ART days 1-3 was determined by linear interpolation from baseline to t = 72 hrs, providing a minimal estimate of maximal HIV-1 RNA decay during this interval. During ART days 4-5, rate of HIV-1 RNA decay in CSF was determined by linear regression analysis of 17 assay results from t = 72 hrs to t = 96 hrs.
Results: Mean baseline HIV-1 RNA in CSF ranged from 3.35-4.68 log10 copies/mL. During ART days 1-3, rate of HIV-1 RNA decay in CSF ranged from 0.11-0.32 log10 [copies/mL]/day (mean = 0.22 [copies/mL]/day). In contrast, the rate of CSF HIV-1 RNA decay during ART days 4-5 ranged from 0.06-0.23 log10 [copies/mL]/day (mean = 0.14 [copies/mL]/day). In every subject, the rate of viral decay during days 1-3 exceeded the rate during days 4-5. The mean ratio of log10 HIV-1 RNA decay rates was 1.86 ±0.18.
Conclusions: In asymptomatic patients, HIV-1 RNA in CSF declines most rapidly during the first 3 days of ART. New insights into HIV pathogenesis in the CNS may result from studying kinetics of this initial CSF HIV-1 RNA decay in different patient groups, or in response to antiretroviral agents with limited CNS penetration. Such a brief sampling interval may allow relative CNS potencies of some antiretroviral agents to be safely assessed as single agents.
