Two phases of HIV RNA decay in CSF during initial days of multidrug therapy

Background: Defining cellular and tissue sources of HIV-1 in CSF is important for understanding disease pathogenesis and optimal therapies for HIV infection in the brain. Objective: To identify the time of maximal viral decay in CSF during the initial days of antiretroviral therapy. Methods: Serial CSF and plasma data were available from four adults who underwent ultraintensive CSF sampling for 48 hours at baseline and again beginning 72 hours after starting antiretroviral therapy. Regression lines were generated using HIV-1 RNA data from 17 on-treatment serial CSF samples obtained at 3-hour intervals. Viral RNA was quantified by Nuclisens(R) and Amplicor HIV-1 Monitor(R) assays. Results: Extrapolation of regression lines intersected baseline below actual baseline CSF HIV-1 RNA concentrations, indicating that virus decayed most rapidly on days 1 through 3 with half-lives of no more than 0.9 to 2.8 days. Half-lives on days 4 and 5 ranged from 1.3 to 4.9 days. Plasma data also showed early rapid decay. Conclusions: Multiple phases of viral decay suggest that virus in CSF originates from at least two sources during untreated, asymptomatic HIV-1 infection. The short half-life indicates that the primary source is CD4(+) T cells. Sampling during days 1 through 3 and different stages of disease will better define sources of virus.