Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection

Objectives: To compare the kinetics and magnitude of HIV-1 RNA responses to antiretroviral therapy (ART) in the cerebrospinal fluid (CSF) and plasma. Design: Repeated lumbar punctures (LPs) were performed after the initiation or change in ART in 15 HIV-1-infected subjects, with the focus on two phas es of response: an acute phase within the first 11 days, for which crude es timates of viral RNA half-lives and decay rates were derived and CSF : plas ma relative decay ratios quantitatively analysed; and a longer-term phase b eyond 4 weeks that was descriptively assessed. Results: In 13 subjects studied during the acute phase, the crude HIV-1 RNA half-life was longer (median 2.0 compared with 1.9 days), the decay rate s lower (median 0.13 compared with 0.16 log(10) copies/day) and, most notably , the variability greater (intraquartile range of half-life 1.8-4.3 compare d with 1.7-2.1 days) in the CSF than in the plasma. A slower decay in the C SF correlated with lower initial blood CD4 T lymphocyte counts (P = 0.001). Seven of 11 subjects studied at 4 weeks or later, including some with slow er acute-phase CSF responses, showed greater or more durable viral suppress ion in the CSF. Conclusion: Divergent acute-phase viral kinetics in the CSF and plasma, and proportionally greater long-term decrements in CSF HIV-1 RNA in slow early -responders or poor overall plasma responders indicate variable compartment alization of CSF infection, consistent with a model of two prototypes of CS F infection: short-lived, transitory infection that predominates in early H IV-1 infection and longer-lived, more autonomous CSF infection predominatin g in late HIV-1 infection. Additional studies will be needed to define more precisely the acute and longer-term CSF kinetics in different clinical set tings and to assess this model. (C) 1999 Lippincott Williams & Wilkins.