Effect of antiretroviral therapy on the cerebrospinal fluid of patients seropositive for the human immunodeficiency virus.
Elevated levels of beta 2-microglobulin and neopterin in cerebrospinal fluid (CSF) have been associated with neurologic complications of infection with the human immunodeficiency virus (HIV). The effect of zidovudine (ZDV) on these markers was assessed by studying the effect of ZDV treatment duration on CSF levels in a cohort of 145 HIV-positive men who were receiving ZDV. CSF beta 2-microglobulin and neopterin levels were significantly lower in those who had been taking ZDV for an intermediate period of time (46-365 days) than in those who had received ZDV either long term (> 365 days) or short term (1-45 days). CSF quinolinic acid levels were independent of duration of ZDV administration. A second CSF evaluation was available after 1 year for 54 HIV-positive men (19 of whom were also in the first cohort) and 11 HIV-negative controls. Patients who had started ZDV between lumbar punctures showed a significant decrease in CSF beta 2-microglobulin, but in those who had been receiving ZDV for > 1 year beta 2-microglobulin increased (p = 0.001). The effect was not observed with neopterin (p = 0.14). (Quinolinic acid levels were not studied longitudinally.) Finally, we observed that CSF levels of beta 2-microglobulin, neopterin, and quinolinic acid correlated strongly with each other in HIV-positive individuals (r = 0.7, p < 0.0001), even though ZDV might have different effects on these markers. In conclusion, we report that initiation of ZDV therapy is associated with a transient decrease in CSF levels of beta 2-microglobulin and neopterin.(ABSTRACT TRUNCATED AT 250 WORDS)
Gulevich
S J
SJ
Department of Neurosciences, University of California San Diego School of Medicine.
McCutchan
J A
JA
Thal
L J
LJ
Kirson
D
D
Durand
D
D
Wallace
M
M
Mehta
P
P
Heyes
M P
MP
Grant
I
I
D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D015496:CD4-Positive T-Lymphocytes; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005947:Glucose / Q000134:cerebrospinal fluid; D006679:HIV Seropositivity / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D006801:Humans; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D017378:Quinolinic Acid / Q000134:cerebrospinal fluid; D015215:Zidovudine / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000134:cerebrospinal fluid
D002556:Cerebrospinal Fluid Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D015215:Zidovudine; D019798:Neopterin; D017378:Quinolinic Acid; D005947:Glucose