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

12th World AIDS Conference

Abstracts 32201-32205 561

32201 Correlation between the viral load in cerebrospinal fluid
(CSF), plasma and CNS involvement in HIV patients
Tengiz Tsertsvadze, N.T. Gochitashvili, R. Sukhiashvili. Georgian AIDS & Clin.
Immunology Center, 16 A4 Kazbegi Avenue, Tbilisi, Georgia
Objectives: The relationship between the CNS manifestations of HIV infection
and the levels of HIV-1 RNA in CSF and plasma were assessed in 23 untreated
HIV patients.
Design: Retrospective case-control study.
Methods: 14 adult HIV patients with CNS manifestations (study group) and
9 adult HIV patients with AIDS defining events, but without neurologic manifestations (control group) were studied. Among the study group 6 patients had
AIDS dementia complex (ADC), 3 patients - CNS Toxoplasmosis, 2 patients -
Progressive Multifocal Leucoencephalopthy (PML), 2 patient - CMV encephalitis
and 1 patient - TB meningitis. Measurement of viral load in CSF and plasma was
performed by RT PCR method. Diagnosis of ADC was made by characteristic
neurologic symptoms and signs that were supported by neurophysiologic assessment and neuroimaging. Diagnosis of CNS opportunistic infections was made by
clinical symptoms, neuroimaging and laboratory investigations (viral and bacterial
cultures, PCR).
Results: HIV RNA in CSF were as follows: in control group - average 574
copies/ml (range undetectable-834), in ADC patients -average 37 000 copies/ml
(range 540-143 700), in TB meningitis - 83 000 copies/ml, in CNS Toxoplasmosis
- average 108 000 copies/ml (range 87 000 7ndash; 139 000), in PML - average
159 000 copies/ml (range 147 000-171 000), in CMV encephalitis - average
163 000 copies/ml (range 152 000-174 000). Viral load in plasma usually was
higher than in CSF. No significant differences in plasma viral load between the
two groups were found.
Conclusions: There is a significant relationship between increased viral load
in CSF and presence of CNS disease. High CSF viral load and CNS involvement
was almost always accompanied by elevated concentrations of plasma HIV RNA
(except of ADC that may be occurred at any level of plasma viral load). And high
plasma viral load not always was accompanied by high levels of HIV RNA in CSF.
S32202 1 Cerebrospinal fluid HIV-1 RNA levels and efavirenz
concentrations in patients enrolled in clinical trials
Karen T. Tashima1, A.M.C. Caliendo2, M.A. Ahmad, J.M.G. Gormley,
T.P.F. Flanigan3, W.D.F. Fiske4. 1164 Summit Ave Providence, RI 02906;
2Massachusetts General Hospital Harvard Univ., Boston, MA; Brown University,
Providence RI; Miriam Hospital, Providence RI; 3Miriam Hospital Brown
University, Providence RI; 4DuPont Merck Pharmaceutical Comapany, Newark
DE, USA
Background and Objectives: Efavirenz is a novel, potent, allosteric inhibitor
of HIV-1 reverse transcriptase administered once daily. We report simultaneous
cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels and CSF and plasma
efavirenz levels in patients enrolled in efavirenz clinical trials.
Methods: In an ongoing longterm study of CSF in patients taking efavirenz in
clinical trials, we measured efavirenz levels in CSF and plasma, and HIV-1 RNA
levels in CSF and plasma after 16 weeks of therapy. CSF efavirenz levels were
determined by liquid chromatography (LC/MS/MS). Plasma samples obtained
at the same time were analyzed by high-performance liquid chromatography
(HPLC) methodology with ultraviolet detection of efavirenz. HIV-1 RNA levels
were performed using the Amplicor HIV-1 Monitor assay.
Results: Mean plasma viral load prior to treatment was 52,963 (range: 16,265
to 108,778). Patients were on combination therapy for a mean of 24 weeks
(range: 17 to 35). Plasma and CSF HIV-1 RNA levels were below the level of
detection (-400 copies/ml) in all eight patients taking efavirenz in combination
with indinavir or with AZT and 3TC. Efavirenz levels will be reported.
Conclusions: Efavirenz in combination with other antiretroviral agents effectively suppresses HIV replication in CSF and plasma in patients. Longitudinal
studies are planned to assess the durability of viral suppression.
32203 | Distribution of brain HIV load in AIDS
Clayton Wiley1, V. Soontornniyomkis1, C. Achim1, I. Mellors1, E. Masliah2,
S. Hermann3, P. Dailey4. 1 University of Pittsburgh, 522 Rodgers Drive Pittsburgh
PA; 2University of California San Diego La Jolla CA; 3Roche Molecular Systems
Branchburg NJ; 4Chiron Diagnostics Emeryville CA, USA
Issue: Approximately one quarter of patients with AIDS develop severe cognitive
deficits called HIV-associated dementia complex (ADC). There is some controversy regarding the importance of viral load in mediating neurologic disease.
Design: Retrospective autopsy study
Methods: We quantified viral load in brains from 10 autopsied HIV-infected
subjects and 2 non-infected controls using sensitive, quantitative and reproducible
RNA assays for HIV load in plasma and CSF.
Results: The new quantitative HIV RNA assays showed general agreement
with previously used semi-quantitative immunocytochemical assessments of HIV

envelope protein, were performed without professional subjective interpretation,
and were truly quantitative. These assays permit ready cross-lab comparison of
the prevalence and importance of viral load in mediating neurologic damage. All
cases with very high levels of HIV in the CSF, had high overall levels in the brain.
Levels of virus in the spleen showed no clear association with those found in the
brain.

Conclusion: CSF viral loads exceeding 106 copies per mL may be a surrogate marker of high viral load in the brain. HIV RNA was not uniformly distributed
throughout the brain. Selective regions, including basal ganglia and hippocampus,
showed higher levels of virus than the cerebellar cortex and mid-frontal cortical
gray matter. Assessment of overall brain viral load requires careful attention to
regional quantitation.
i 322041 In vivo proton MRS studies of HIV brain injury and HIV
dementia
R. Lenkinski13, Bradford Navia1, L. Lee2, T. Ernst3, C. Yiannoutsos4, J. Jarvik5
C. Marra5, D. Meyerhoff6, R. Price6, D. Simpson7, S. Atlas7, U. Patel8,
G. Schifitto8, S. Swindells9, J. McConnell9, R. Omaha10, J. Videen10,
R. McKendall11, L. Ketonen11, K. Goodkin12, T. Naidich12, J. Post12, D. Kolson13,
L. Chang3, R.G. Gonzalez2. 1Research Laboratories in Psychiatry, Box 1007,
New England, Medical CTR, Boston MA002111; 2Massachusetts General
Hospital, Boston, MA; 3University California Los Angeles, Los Angeles, CA;
4Harvard School of Public Health, Boston, MA; 5University of Washington,
Seattle, WA; 6 University of California San Francisco, San Francisco, CA; 7Mt
Sinai Medical Center, New York, NY; 8University Rochester, Rochester, NY;
9University Nebraska, Omaha, NE; 1~University California San Diego, San
Diego, CA; 11 University Texas, Galveston, TX; 12University Miami, Miami, FL;
13University Pennsylvania, Philadelphia, PA, USA
Background: Proton magnetic resonance spectroscopy (1HMRS) provides a
sensitive in vivo method to examine the pattern and extent of cerebral injury in the
HIV infected brain and to monitor response to novel therapies. 1HMRS studies
have reported a reduction in N-acetyl aspartate, a marker of mature neurons, in
subjects with the AIDS dementia complex (ADC), consistent with reported findings
of neuronal injury or loss as well as elevations in choline and myoinositol during
earlier stages of infection, possibly reflecting changes in glia cell metabolism
or membrane turnover. The significance of these findings, however, and their
relationship to the severity of neurologic and systemic disease remain to be
determined.
Methods: To address these issues, we have formed the first multisite in vivo
1HMRS study of HIV brain injury in the US involving ten centers. The scientific
aims of this consortium are: 1) To quantify regional levels of NAA, choline, myoinositol in a well defined cohort of subjects with ADC, compared to age matched
HIV subjects without ADC and HIV negative controls. 2) To relate regional measurements of these metabolites to: the severity of neurocognitive impairment and
systemic disease; patterns of antiretroviral therapy; plasma and CSF studies of
viral load; and levels of surrogate markers of immune activation and neurotoxicity; 3) To determine the effect of memantine, an NMDA receptor antagonist
that effectively prevents HIV-related neurotoxicity, on the levels of these cellular
metabolites.
Results: Spectra are obtained from the parietal gray matter, frontal white
matter, and basal ganglia on a 1.5T GE Signa scanner with operating system
Horizon 5.6, using Probe-P. To establish intersite reliability, we have obtained and
compared metabolite measurements using phantom references from 5 centers
and from 7 HIV negative controls from 4; results from phantoms are: NAA/Cr
1.60 ~ 0.05, Cho/Cr 0.77 ~ 0.03, MI/Cr 0.35 + 0.02; results from normals by
region are: parietal 1.56 ~ 0.06; 0.60 ~ 0.050, 0.55 ~ 0.04, centrum semi-ovale
1.8 ~ 0.1, 1.0 ~ 0.2, 0.50 ~ 0.04; basal ganglia 1.4 ~ 0.2, 0.74 ~ 0.08, 0.48 ~
0.08. Futher analysis indicates excellent agreement of metabolite measurements
across several sites.
This is first demonstration of intersite reliability using this protocol with the
current operating system. The results will allow us to pursue a multisite in vivo
study of HIV induced brain injury and to identify novel therapies that may reverse
the cellular abnormalities and the clinical syndrome.
32205 Oligosymptomatic neurological patients in a cohort of
HTLV-I infected people
Abelardo AraLjo, A.C.C. Leite2, E.S. Neves2, A.L.A. Oliveira2, C.R. Afonso2,
O.J.M. Nascimento3. 1Rua Gal Rualino Olivveira, Rio De Janeiro; 2Fundagao
Oswaldo Cruz, Rio De Janeiro, RJ; 3 Universidade Federal Fluminense, Niteroi,
RJ, Brazil
Objective: Determine the frequency of neurological symptoms and/or signs in a
cohort of HTLV-I positive blood donors of Rio de Janeiro, Brazil.
Design: Cross-sectional study.
Methods: 151 HTLV-I positive blood donors from the largest blood center of
Rio de Janeiro with no other known causes for neurological syndromes were
included, from June 1996 to June 1997. Patients were submitted to an interview
and neurological examination during a baseline visit. When applicable MRI, EMG,
CSF and nerve biopsy studies were performed.
Results: 22/151 (14.6%) patients had neurological signs/symptoms. Three
basic patterns emerged from this group: (1) Patients with neurological complaints
and abnormal neurological examination - 6/151 (4%); (2) Patients with no complaints and an abnormal neurological examination - 11/151 (7.3%); (3) Patients

with neurological complaints but with a normal neurological examination - 5/151
(3.3%). In group 1, four patients had evidences for subclinical HTLV-I myelopathy,
one had a radiculitis and one a subclinical polyneuropathy. In group 2, nine patients had an axonal sensory-motor polyneuropathy, one a motor neuron disease
and one increased deep reflexes in the lower limbs. In group 3 the complaints
were mainly vague paresthesiae, weakness, lumbar pain and impotence.