translation agency

Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection.
Staprans S; Marlowe N; Glidden D; Novakovic-Agopian T; Grant RM; Heyes
November 30, 1999
AIDS. 1999 Jun 18;13(9):1051-61. Unique Identifier : AIDSLINE

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 phases of response: an acute phase within the first 11 days, for which crude estimates of viral RNA half-lives and decay rates were derived and CSF:plasma relative decay ratios quantitatively analysed; and a longer-term phase beyond 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 slower (median 0.13 compared with 0.16 log10 copies/day) and, most notably, the variability greater (intraquartile range of half-life 1.8-4.3 compared with 1.7-2.1 days) in the CSF than in the plasma. A slower decay in the CSF 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 slower acute-phase CSF responses, showed greater or more durable viral suppression 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 compartmentalization of CSF infection, consistent with a model of two prototypes of CSF infection: short-lived, transitory infection that predominates in early HIV-1 infection and longer-lived, more autonomous CSF infection predominating in late HIV-1 infection. Additional studies will be needed to define more precisely the acute and longer-term CSF kinetics in different clinical settings and to assess this model.

JOURNAL ARTICLE Adult Anti-HIV Agents/*THERAPEUTIC USE AIDS Dementia Complex/*DRUG THERAPY/*VIROLOGY Comparative Study CD4 Lymphocyte Count Drug Therapy, Combination Human HIV Protease Inhibitors/THERAPEUTIC USE HIV-1/*PHYSIOLOGY Male Quinolinic Acid/BLOOD Reverse Transcriptase Inhibitors/THERAPEUTIC USE RNA, Viral/BLOOD/*CEREBROSPINAL FLUID Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Time Factors Treatment Outcome Viral Load