       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).

