Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

562 Abstracts 32206-32211

12th World AIDS Conference

Conclusion: Symptoms and/or signs of neurological disfunction can be found
in 14.6% of HTLV-I infected blood donors with no other known causes for neurological syndromes. The most common clinical finding in such individuals is an
axonal sensory-motor polyneuropathy. Subclinical HTLV-I myelopathy is found in
2.6% of patients.
32206 Symptoms and signs of peripheral neuropathy in HIV
infected children
Alexandra Araujo. Rua Gal Raulino de Oliveira 124/202 Rio de Janeiro
22620-330, Brazil
Objective: To search for clinical findings of peripheral neuropathy in a series of
HIV infected children from Brazil.
Design: Descriptive study.
Method: HIV infected children older than 5 years of the HIV out-patient clinic
of the Federal University of Rio de Janeiro were included. Patients without confirmation of their HIV status were excluded. They were interviewed and examined
systematically for peripheral nerve symptoms and signs. Nutritional status, current
and previous treatment regimens, length of HIV infection diagnosis and current
HIV classification were recorded.
Results: A total of 39 patients were evaluated. Their age ranged from 5 to
14 years, 25.6% (10/39) had symptoms and signs of peripheral nerve involvement, 28.2% (11/39) had only symptoms, 17.9% (7/39) had only signs and 28.2%
(11/39) had neither. Distal paresthesia and/or pain plus diminished Achiles tendon
reflex and/or diminished vibration sense were the most common clinical findings.
Presence of those symptoms and signs of peripheral neuropathy had no clear
correlation with nutritional status, neurotoxic drug exposure, disease duration or
classification in this group of patients.
Conclusion: Peripheral neuropathy is found in HIV infected children. More
studies are needed to determine the risk factors related to this disorder in this
age group.
S564*/32207 Stavudine stops neuro-AIDS in
AZT-non-responders
Gabriele Arendt2, H.-J. v. Giesen2, H. Jablonowski1. 'Dept of Neurology and
Medicine; 2University of Duesseldorf, FRG
Objectives: The effectivity of stavudine in HIV-1 positive patients with deteriorating mental and motor status under long-term AZT-treatment was tested.
Design: controlled
Methods: 78 HIV-1-positive patients with deteriorating mental status and motor performance (motor test battery's. Arendt et al., J. Neurol. 1990) under AZT
long-term therapy (group 1) and 21 patients under the same clinical conditions
with no prior antiretroviral therapy (ART) (group 2) were switched or started
on a stavudine (D4T) medication (60-80 mg/day). 42 patients with new onset
AZT/ddC or AZT/3TC medication (group 3) served as controls. The three groups
were comparable with respect to age, sex, duration of HIV-1 positivity, distribution
to risk groups and CDC-stages.
Results: Whereas in group 1 and 3 motor values revealed no significant improvement, but at least no further deterioration during the observation period
of 12 months, patients in group 2 showed therapy effects in the most sensitive
motor value (contraction time = CT: 154.2 ~ 43.2 ms vs. 132.1 ~ 25.0 ms) and a
stabilisation of their mental status after the one year follow-up.
Conclusions: (1) Change of ART or new onset of D4T therapy stops NeuroAIDS. (2) In HIV-1-positive and AIDS-patients deteriorating neurologically under
AZT-therapy a switch to D4T improves the patients' clinical status and motor
performance.
S32208 Neurocognitive complications in HIV
Igor Grant, R.K. Heaton, R.O. Ellis, E. Masliah, TD. Marcotte, L.K. Dawson,
A.J. McCutchan. Dept. of Psychiatry (0680), Univ. California, San Diego, La
Jolla, CA 92093-0680, USA
Background: Neurocognitive complications of varying severities occur in HIV
disease. Their neurobiologic bases and predictors are not well understood.
Methods: We performed detailed neuropsychological (NP) testing, CSF viral
load measurements, and postmortem correlative studies using immunostaining
for microtubule associated protein (MAP-2) and synaptophysin (SYN).
Results: In the HNRC series of 637 HIV+ persons (CDC-A = 397; CDC-B =
154; CDC-C = 86), we noted 29% to have asymptomatic NP impairment, 12%
with minor cognitive motor disorder (MCMD), and 2% with HIV dementia (HAD).
The rates of MCMD rose from 4.8% in CDC-A to 24.4% in CDC-C and those
of dementia from 0.8% in CDC-A to 7% in CDC-C. Dendritic simplification is a
substate for these neurocognitive impairments, as illustrated by strong association between percent area occupied by MAP-2 - a measure of post-synaptic
injury - and antemortem degree of NP impairment (r (20) = -.59, p =.003). NP
impairment is associated with increased viral load in the CSF (not plasma), but

this relationship obtains only in late stage disease.
Conclusions: Even mild NP deficits appear to have biological correlates (injury
to synaptodendritic apparatus) and in advanced disease is predicted by rise in
CSF but not plasma viral load.

32209 1 Regression or stabilization of PML by highly active
antiretroviral therapy (HAART) and acyclovir therapy
Alberto Acosta. The New York Hospital, Cornell Medical, New York. NY USA
Issue: Progressive Multifocal Leukoencephalopathy (PML) is a severe neurologic
AIDS-related disease with no adequate therapy. Regression of PML has been
previously reported in one patient who received HAART
Project: Two HIV+ patients on combination therapy with reverse transcriptase
inhibitors (RTI) presented with neurologic findings. Patient 1 (PT 1): 24 year old
male hemophiliac with a rapidly progressive right sided hemiparesis. Brain MRI
revealed a mass in the left frontal parietal area. Patient 2 (PT 2): 54 year old
male with memory loss and confusion. Brain MRI revealed diffuse periventricular
white matter disease. Both patients declined brain biopsy. The diagnosis of PML
was made by exclusion: brain MRI findings consistent with PML; negative brain
SPECT thallium scan; negative CSF studies including cytology, CMV PCR, and
bacterial, fungal and AFB cultures. RTI therapy was changed: PT 1 - didanosine &
stavudine; PT 2 - zidovudine & lamivudine. Treatment with indinavir and acyclovir
was also initiated in both patients. Clinical and neurologic status were closely
monitored and serial brain MRI scans were performed.
Results: Both patients showed improved neurologic status within 8 weeks after
initiation of therapy. PT 1 demonstrated improved right sided motor strength with
brain MRIs revealing decreasing PML size for 21 months. CD4 counts increased
from 86 to 177. No baseline HIV mRNA PCR was available but subsequent
values were <400. PT 2 had improved cognition to his pre-morbid level despite
no change in brain MRI for 18 months. CD4 count increased from 50 to 66 and
mRNA PCR decreased from 365,840 to <400.
Lessons Learned: Two HIV+ patients with PML had significantly improved
clinical and neurologic status after treatment with HAART and acyclovir therapy.
Brain MRIs revealed decreased PML size in one patient and no change in the
other. HAART and acyclovir therapy may be beneficial in the treatment of PML in
HIV+ patients.
1 32210 Detection of JC virus (JCV) DNA in blood cell
subpopulations and plasma of HIV+ individuals and
HIV- controls with and without progressive multifocal
leukoencephalopathy (PML)
Igor J. Koralnik, J.E. Schmitz, D. Boden, V. Mai, N.L. Letvin. Harvard Medical
School, MA, USA
Objectives: To investigate the relationship between JCV detection in the blood
and the diagnosis of PML, and to determine which blood cell subpopulation carries
JCV.
Methods: Peripheral blood mononucleated cells (PBMC), granulocytes and
plasma samples were obtained from HIV+ patients and HIV-controls, with and
without PML, after isolation on a double centrifugation gradient. PBMC subpopulations were isolated by flow cytometric sorting. JCV DNA was detected by
polymerase chain reaction (PCR). The diagnosis of PML was made using clinical
and radiologic criteria together with positive JCV PCR in the cerebrospinal fluid
or a brain biopsy.
Results: JCV DNA was detected in 4/7 PBMC and 2/6 plasmas of HIV+/PML
patients, 12/102 PBMC and 7/17 plasmas of HIV+ people without PML, 2/5
PBMC and 2/4 plasmas of HIV-/PML patients, 1/2 PBMC and 1/2 plasmas
of immunosuppressed HIV- patients without PML, but in 0/18 PBMC and 0/13
plasma samples of normal HIV- controls. There was no correlation between the
detection of JCV in PBMC and plasma, but both were associated with low CD4
counts in HIV+ persons. JCV became undetectable in the PBMCs of 2 patients
after treatment with HAART, as their CD4 counts rose from <20/iil to >100/jil.
Either B cells, T cells, monocytes or granulocytes were found to harbor JCV DNA
in 10 evaluated patients.
Conclusions: JCV detection in the blood is not specific for PML, but correlates
with the degree of immunosuppression in HIV infection. JCV is not found in the
blood of normal immunocompetent persons. JCV is carried by multiple blood cell
populations, and can be detected in cell-free plasma samples as well. JCV detection in the blood does not constitute a useful surrogate marker for the diagnosis
of PML and would be of limited value in monitoring clinical treatment trials.
|32211 | Latency of event-related brain potential P3a is associated
with cognitive impairment in HIV disease
Daniel Fletcher1, R. Bitner2, K. McCallin2, G. Fein2. 14150 Clement Street 116R,
San Francisco, CA 94121; 2UCFS, San Francisco, CA, USA
Background: Subcortical gray matter, frontostriatal and frontothalamic white
matter tracts are the brain structures affected earliest in HIV disease. This is a
replication of a previous study investigating the latency of the P3a electrophysiological response as a measure of the effects of HIV disease on frontal cortex
function.
Methods: An auditory oddball paradigm was utilized to elicit P3a and P3b at
30 scalp electrodes in 54 HIV+ subjects and 19 controls. Stimuli were 52 msec

in duration and consisted of: standard - 1000 Hz tone (70% of trials), target
- 2000 Hz tone (15% of trials), novel non target - excerpts of sound effects
tape (15% of trials). N100, P200, P3a, and P3b responses were identified with
topographic maps. Amplitude and latency were chosen from the channel closest
to the peak in the topography. Neuropsychological tests in 10 cognitive domains
were administered and age-adjusted z-scores calculated.