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

12th World AIDS Conference

Abstracts 32212-32216 563

Results: Severely cognitive impaired HIV+ subjects exhibited increased P3a
latencies compared to controls (324.8 ~ 22.8 msec vs. 356.0 ~ 37.7 msec,
two-tailed t-test, p --.01) but no differences were found in P3a amplitude or P3b
amplitude or latency (all p's -.3). P3a latency and neuropsychological test results
were correlated in the motor (r = -.463, p <.001) and psychomotor (r = -.436,
p -.002).
Conclusion: This study provides further evidence for our model that P3a latency is affected by damage to frontal cortex inputs and is therefore a sensitive
index of the CNS effects of HIV disease progression. This suggests that it may
be useful for monitoring treatment response and for studies investigating CNS
manifestations of HIV disease.
32212 Amantidine and other endocytic pathway blockers inhibit
HIV infection of astrocytes
William D. Lyman, H.N. Hao. 3901 Beaubi en Children's Hospital of MI CRCM
3K42 Detroit, Michigan 482 01-2196, USA
Objectives: To test the hypothesis that HIV infects astrocytes via an endocytic
pathway. In addition, to determine if pharmacologic agents that can disrupt this
pathway and that can currently be prescribed for humans are reasonable candidates for the treatment of some of the central nervous system sequelae of HIV
infection.
Design: Laboratory study using an in vitro human fetal astrocyte culture model
for HIV neuropathogenesis. and molecular biologic techniques to investigate
the potential that HIV infects this cell type via an endocytic pathway (i.e., endosome/lysosome). To test this hypothesis, three pharmacologic agents (amantidine,
chloroquine and monensin) known to disrupt endocytosis were studied. Of these
drugs, amantidine may hold the most promise for the treatment of HIV/AIDS
because it may not only reduce HIV infection of neural cells but may also be
useful due to its known benefit in treating people with tremor-at-rest or other
signs or symptoms of Parkinson's disease, which are common manifestations
associated with neuroAIDS.
Methods: Cultures of normal human fetal astrocytes were established. The cell
cultures were exposed to either HIV alone or to HIV and 1 mM amantidine, 0.4 to
1 mM chloroquine, or to 1 to 10 pM monensin. A quantitative estimation of HIV
infection of cultured cells was determined by HIV DNA PCR and cell cytotoxicity
assays.
Results: Amantidine treatment of cultured cells resulted in a complete (100%)
reduction in HIV infection of astrocytes. Chloroquine and monensin reduced HIV
infection of astrocytes by 24 to 76% and 16 to 58% respectively. None of the
pharmacologic treatments resulted in cell death as the concentrations of the drugs
used were significantly below their LD50's.
Conclusions: HIV infection of human fetal astrocytes appears to be mediated
by an endocytic pathway. Evidence to support this conclusion is based on a
principal pharmacologic action of each of the drugs tested in this study, namely
the drug's ability to reduce the acidification of lysosomes. Because of these data
and the current approved use of amantidine, this drug may be considered for the
management of HIV-infected people.
32213 Central nervous system infection by prototheca
wickerhamii in an HIV infected patient
Juan Carlos Rosso Vedeal, F. Saddy, M.L.A. Toscano Concha, G.A. Martins,
S.A. Silva. Hospital Municipal Miguel Couto, Rio de Janeiro, Brazil
Background: Protothecosis is an uncommon infection caused by the ubiquitous
achlorophylic algae Prototheca wickerhamii. Occupational exposition with cutaneous infection, olecranean bursitis, disseminated visceral disease and one case
of meningitis have been previously described in AIDS patients.
Objective: To describe a case of meningeal protothecosis in a patient with
AIDS.
Case Report: A 32 years old male, countryside resident, intravenous drug user,
homosexual and previously healthy was admited in the intensive care unit with
acute respiratory failure (PaO2/FiO2 = 78 and lung injury score of 3.5), meningeal
signs and a septic shock profile by invasive hemodynamic monitoring. The computed tomography study of the brain was normal. A large spectrum antibiotic
therapy including Anfotericin B was initiated. The serum anti - HIV test was positive. The CD4+ count was 40 cells/mm3. The cerebrospinal fluid (CSF) analysis
revealed a clear liquor with 4 cells/mm3, 100% monocytes, proteins: 42 mg/dl,
glucose: 60 mg/dl. The immunological tests for Syphilis, Cytomegalovirus, Herpes
simplex, HTLV-1, Cysticercosis and Toxoplasmosis were negative. The microbiological studies for fungus and mycobacteria were negative. The microscan test
identified Prototheca wickerhamii. The patient presented clinical improvement
without neurological sequelae and was discharged from hospital 30 days after
admission.
Conclusions: We report a rare central nervous system infection caused by
Prototheca wickerhamii as first presenting disease in an HIV positive patient
from a rural area, who was treated effectively with Anfotericin B and adequate
hemodynamic and respiratory support.

S32214 Tuberculosis of the central nervous system in HIV
infected patient
Luis Espinoza', M.J. Gold2, J. Witek2, A. Singler2. 'Broad & Vine, MS 405
Philadelphia, PA 19102; 2Allegheny University Of Health Sciences Philadelphia
PA, USA
Background: Mycobacterium Tuberculosis (TB) of the Central Nervous System
(CNS) in HIV infected patients has a very high mortality. It is usually associated
with a delay in starting antituberculosis therapy since cerebrospinal fluid (CSF)
cultures may take up to 8 weeks. We studied the clinical presentation and CSF
findings in CNS TB to identify factors which can lead to a prompt diagnosis and
treatment.
Materials: 22 patients with HIV infection and CNS TB were identified over a
5 year period in a general hospital. TB of the US was based upon positive CSF
culture in 20 patients, brain biopsy on 2 and/or autopsy findings in 3 patients.
Relevant clinical data and CSF findings were analized.
Results: 1) 11 (50%) patients had a history of pulmonary TB and 6 (27%). had
no prior opportunistic infection. 2) Their CD4 count range from 9 to 331 (median
136). 3) Clinical presentation included fever/headache (72%), changes in mental
status (45%), neurologic focalization (27%) and nausea/vomiting (18%). 4) CSF
protein range from 44 to >900 mg/L (median 328) and CSF glucose from <10 to
109 mg/dl (median 30). 5) Sensitivity for CSF cultures were as follows: 11 were
sensitive to all drugs tested (isoniazid, rifampin, ethambutol, streptomycin), one
was resistant to one drug, four to 2 drugs and another four were resistant to >3
drugs. 6) 13 (59%) patients died within the first 2 months of diagnosis and another
3 before de fifth month; only 3 patients were living after 18 months and 3 were
lost of follow-up.
Conclusions: HIV patients with CNS TB have a clinical presentation and CSF
profiles similar to those seen in non-HIV individuals. Patients with a history of
pulmonary TB or opportunistic infections who present with meningeal signs and
CSF abnormalities suggesting CNS TB should promptly be started on adequate
anti-TB regimen and the use of other techniques (X-rays, MRI, PCR) should be
sought to confirm this diagnosis.
32215 Volume reductions of subcortical nuclei in HIV+ subjects
are correlated with the severity of cognitive impairments
Victoria Di Sclafani1, B. Chung2, M. Tolou-Shams2, L. Kusdra2, G. Fein2. '4150
Clement St. 116R, San Francisco, CA 94121; 2UC San Francisco, San
Francisco, CA, USA
Background: HIV-associated CNS neuro-cognitive impairments have the characteristic pattern of a subcortical dementia. Caudate nucleus volume reductions
have been demonstrated in HIV disease, with the magnitude of the volume
reduction correlated with the severity of neuro-cognitive impairment.
Methods: We measured caudate, thalamus, putamen and globus pallidus volumes from Magnetic Resonance Images in 41 HIV controls and in 68 HIV+
subjects whose CD4+ counts were less than 200. Neuropsychological function
was assessed by an extensive battery of tests.
Results: Volumes of the subcortical nuclei were reduced in the HIV+ subjects
compared to controls. The magnitude of the HIV-associated volume reduction
in subcortical nuclei was positively correlated with the severity of global neuropsychological impairment and with the severity of impairment in the attention,
abstraction, psychomotor, motor and learning domains. The subcortical volume
reductions will be compared to measures of regional cortical gray matter atrophy
and with the volume and severity of white matter hyperintensity.
Conclusion: Subcortical nuclei are vulnerable to HIV infection. Volume reductions in subcortical nuclei reflect an aspect of the HIV disease process resulting
in neuropsychological impairments in HIV+ subjects.
32216 Meningitis in a community with a high seroprevalence of
HIV infection
Eli Silber', P. Sonnenberg2, K.C. Ho3, H.J. Koornhof4, S. Eintracht4, L. Morris5,
D. Saffer6. Dept of Neurology, UMDS, Guy's Hospital London SE19RT, UK;
2Community Health, Univ. Witwatersrand, Johannesburg, 3Gold Fields West
Hospital, Westonaria; 4SAIMR/University of the Witwatersrand, Johannesburg;
5National Institute for Virology, Johannesburg; 6Baragwanath Hospital, Univ.
Witwatersrand, Johannesburg,, South Africa
Background: The HIV pandemic has resulted in an increased incidence and a
change in the spectrum of neurological infections, both in causative agents and
clinical manifestations.
Objectives: To evaluate the spectrum of aetiologies of meningeal infection in
a community with a high prevalence of HIV infection, and to correlate these with
clinical and laboratory features, HIV status and level of immune deficiency.
Design: A prospective cohort of 60 consecutive lumbar punctures (LPs), performed for suspected meningitis.
Setting: A hospital serving a workforce of 28 500 gold miners, originating from
rural areas of Southern Africa.

Results: 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of whom had
a CD4 count <200 cells/mm3. 9 patients had tuberculous meningitis (TBM) and
2 tuberculomas. 13 patients (22.8%) had been treated for TB, and 4 developed
CNS TB whilst on therapy. There was one case of multidrug, and two cases of
isoniazid resistant TBM. There were 9 episodes of cryptococcal meningitis in 7
patients, three of whom had a concurrent CNS infection - TBM, neurosyphilis and
a tuberculoma. Acute bacterial meningitis was diagnosed in 12 patients, 9 due to