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M9620850.TXT
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1996-02-26
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Document 0850
DOCN M9620850
TI Quantifying HIV-1 RNA using the polymerase chain reaction on
cerebrospinal fluid and serum of seropositive individuals with and
without neurologic abnormalities.
DT 9602
AU Conrad AJ; Schmid P; Syndulko K; Singer EJ; Nagra RM; Russell JJ;
Tourtellotte WW; Neurology Services, VA Medical Center West Los
Angeles,; California 90073, USA.
SO J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Dec 1;10(4):425-35.
Unique Identifier : AIDSLINE MED/96074275
AB We quantified HIV-1 RNA levels (copies per milliliter) in cerebrospinal
fluid (CSF) and serum from subjects at various stages of HIV-1 disease
and determined the relationship of RNA levels to clinical and neurologic
disease status (HND) and to laboratory values. Ninety-seven
HIV-1-seropositive men without CNS opportunistic infections, tumors, or
neurosyphilis and 13 high-risk seronegative controls were included in
the study. Each individual underwent a structured interview and physical
and neurologic examinations, followed by standardized collection of
blood and CSF. A custom-designed, fully automated polymerase chain
reaction (PCR) system was used to perform a minimum of four separate
amplifications per specimen, using two HIV-1 gag primer pairs. Southern
blotting followed by hybridization with product-specific probes was used
for post-PCR detection. The number of copies per milliliter was
determined by relating unknowns to a built-in dilution-series standard
curve using an image analysis system. HIV-1 RNA was detectable in 96% of
the sera, 78% of the concentrated CSF samples, and 54% of the
unconcentrated CSF samples. Serum RNA levels were significantly higher
than in CSF. Serum RNA levels were significantly inversely correlated
with CD4+ cell counts (p = -0.34; p = 0.03): i.e., higher RNA levels in
seropositive subjects were associated with lower numbers of CD4+ cells.
Serum RNA levels correlated positively with number of AIDS-related
symptoms, dysfunction scores for total neurological examination, mental
status score, cranial nerve score, and CNS motor signs score. Serum RNA
levels did not correlate significantly with length of time on zidovudine
therapy, intrathecal IgG synthesis rate, or albumin leakage. RNA levels
in CSF significantly correlated only with intrathecal IgG synthesis rate
and with serum RNA levels. These results confirm that serum levels of
HIV-1 RNA correlate with HND and inversely correlate with CD4 counts,
demonstrating that HND occurs predominantly in late stages of HIV-1
disease, although HIV-1 RNA can be detected in CSF from a majority of
HIV-1-seropositive individuals at all stages of disease, which suggests
that there can be early penetration of HIV into the CNS. However, HND
can occur in the absence of high levels of CSF HIV-1 RNA. We also found
that the concentration of HIV-1 in CSF is correlated with intrathecal
IgG synthesis rate.
DE Adult AIDS Dementia Complex/BLOOD/CEREBROSPINAL FLUID/*DIAGNOSIS Base
Sequence Blotting, Southern Cerebrospinal Fluid/VIROLOGY CD4
Lymphocyte Count CD4-Positive T-Lymphocytes/VIROLOGY DNA
Primers/CHEMISTRY Gene Products, gag Human HIV
Seropositivity/BLOOD/CEREBROSPINAL FLUID/*DIAGNOSIS
HIV-1/*GENETICS/ISOLATION & PURIF Male Molecular Sequence Data
Polymerase Chain Reaction/*METHODS RNA, Viral/*BLOOD/*CEREBROSPINAL
FLUID Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S.
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).