Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection.
OBJECTIVE
To compare the kinetics and magnitude of HIV-1 RNA responses to antiretroviral therapy (ART) in the cerebrospinal fluid (CSF) and plasma.


METHODS
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.


CONCLUSIONS
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.
Department of Medicine, University of California, San Francisco, USA.
S
S
Staprans
N
N
Marlowe
D
D
Glidden
T
T
Novakovic-Agopian
R M
RM
Grant
M
M
Heyes
F
F
Aweeka
S
S
Deeks
R W
RW
Price
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000821:virology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D017378:Quinolinic Acid / Q000097:blood; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D017378:Quinolinic Acid