Final Program and Oral Abstracts [International Conference on AIDS (8th: 1992: Amsterdam, Netherlands)]

THURSDAY, 23 JULY 1992

ThB 1508-ThB 1513

Th 1508 ANONYMOUS QUESTIONNAIRE TO ASSESS
Ih 15?08 CONSUMPTION OF PRESCRIBED AND ALTERNATIVE MEDICATION AND PATTERNS OF
RECREATIONAL DRUG USE IN A HIV POSITIVE POPULATION
Valentine. Christopher B: Weston, R; Kitchen,V; Main, J; Moncrieff, KC* and Aber, VR*
St Mary's Hospital, Paddington, LONDON W2 and *MRC HIV CTC, LONDON, UK.
Objectives: To establish patterns of usage of prescribed medication, alternative medication consumption, the beliefs of
our patients surrounding these agents and patterns of recreational drug use.
Methods: All patients attending our HIV clinic during a representative 2 week period were asked to complete an
anonymous self-administered questionnaire The data which was analysed by SAS and BMDP statistical software.
Results: Ninety-nine patients returned the questionnaire.(response rate 82%). 93% of the respondents were gay or
bisexual men. The mean age was 36 with a range of 21-67. The patients were taking an average of 3 (range 0-10)
medications prescribed by the clinic. Only 8% reported getting prescribed medications from any other source (their general
practitioner). No patient reported obtaining medications on the "black market".
53% were taking other or alternative medications the most commonly used of which was vitamins with 60% reporting
that they are or have been taking vitamins in the past. The patients generally felt that drugs prescribed from the clinic
were helping them; only 4 patients feeling that these medications were harming or not helping them. Most patients did
not feel that alternative medications are better than prescribed medicines and 12% did not feel they complemented
prescribed medicines. Alternative medications are perceived to be safe.
In the three months prior to the survey, only one patient reported that he did not drink alcohol, 68% of the respondents
reported drinking alcohol at least twice a week, 62% smoke cigarettes every day and only 24% are non-smokers. 78% used
'poppers', 46% cocaine, 48% ecstasy and 78% cannabis. Other recreational drugs were taken.
Conclusions: Patients receive a large number of drugs from the clinic which they generally perceive to be helping.
They also take alternative medicines which are perceived to be safe but not better than conventional medicines.
Recreational drug use is common.
Valentine, Christopher B, St Mary's Hospital Medical School, Norfolk Place,
Paddington, LONDON W2, United Kingdom.
Tel: [phone], Fax [phone]
ThB 1510 UTILITY OF HIV-1 P24 ANITGEN
MEASUREMENT IN CSF FROM PATIENTS WITH AND WITHOUT
COGNITIVE IMPAIRMENT. Royal. Walter III. Concha M, McArthur JC, Selnes
OA, Nance-Sproson TE, Johns Hopkins School of Medicine, Baltimore, MD, USA
Objective: To determine the relationship between CSF measurements of HIV-1 p24 antigen (p24Ag) in samples
from HIV-1 seropositive individuals and the presence of HIV-related dementia.
Methods: Blood (plasma or serum) and CSF samples were assayed for p24Ag in antigen capture EIA following
treatment in acidic buffer (Coulter, Hialeah, Fl.). The frequency of antigen detection was compared for
individuals with no cognitive impairment (NL), cognitive impairment with no evidence of dementia (NP+), and
individuals diagnosed with HIV-related dementia (DM). Statistical analyses were performed using parametric
and non-parametric tests where appropriate.
Results: P24Ag assays were performed on 84 blood and 72 CSF samples from 65 individuals. Peripheral blood
median CD4+ cell counts were 561.5, 300.5, and 190.0 per mm3 for the NL, NP+, and DM group, respectively
(p<0.001). In blood p24Ag was positive among 32/41 (78%) NL, 18/27 (67%) NP+, and 14/16 (88%) DM
samples (NS). In CSF 2/26 (8%) NL, 3/37 (8%) NP+, and 9/23 (39%) DM samples were positive for p24Ag
(p= 0.002). Among samples from DM subjects the sensitivity of the p24Ag assay in CSF was, therefore, 39%,
specificity 92%, positive predictive value 64%, negative predictive value 81%, and the efficiency 78%.
Conclusions. HIV-1 p24Ag can be detected in the CSF of individuals with HIV dementia using acid-treated
samples in this antigen capture assay. The high specificity and negative predictive values for this assay suggest
that this test is useful in the diagnosis of dementia related to HIV-1 infection.

ThB 1509 CCOGNITIVE DEFICIT & NEUROLOGICAL
T 1 5 9 IMPAIRMENT IN PEDIATRIC HIV
Stein. Zena,* ** Mellins CA,* Levenson Jr., RL,* Zawadzki R,*
Kairam R.***. * HIV Center for Clinical & Behavioral Studies, NYS
Psych. Inst., New York, NY, USA; ** Columbia University, New York,
NY, USA; *** St. Lukes Roosevelt Hospital, New York, NY, USA
Objective: To explore the potential contribution to cognitive functioning oft HIV
infection, neurological impairment, and pre-natal drug-exposure.
Method: 49 children who were HIV-exposed and between the ages of 2.5 and 8.5 years
received neurological (standard clinical examination) and psychological (McCarthy
Scales of Children's Abilities) assessments in a pediatric neurology clinic.
Eight children were seroreverters, all neurologically normal, 29 children were
HIV-infected with no neurological impairment, and 12 children were HIV-infected
with neurological deficits. All eight of the seroreverters, and 22 of the 41 HIV+
children, were pre-natally drug exposed.
Results: The mean level of cognitive functioning for this sample was in the
Borderline range, with 39% of the sample scoring in the Mentally Retarded range.
There were no differences in cognitive functioning between Seroreverters and
HIV+ children who did not yet have neurological deficits. However, HIV+ children
with neurological impairment scored considerably below the other two groups on the
General Cognitive Index, and the Quantitative and Memory Scales (Means in the
Mentally Retarded range). No differences could be attributed directly to
drug-exposure.
Discussion: There were no apparent differences in cognitive functioning associated
with HIV status alone or drug exposure alone. Nevertheless, both HIV-infected and
seroreverted children demonstrated significant cognitive deficits compared to
national standards. However, the presence of neurological impairment in HIVinfected children markedly intensified these deficits. These results suggest that
although drug exposure and cultural deprivation may result in decreased cognitive
performance in children, regardless of HIV status, with the advent of neurological
impairment, presumably HIV associated, children are at additional risk for
functioning in the Mentally Retarded range.
Zena Stein, M.A., M.B., B.Ch.
NYS Psych. Inst., Box 53, 722 West 168 Street
New York, NY 10032, USA Phone [phone] Fax [phone]
Th B 1 511 QUINOLNIC ACID AND THE PATHOGENESIS OF AIDS DEMENTIA. Brew. Bruce ames*. Corbeil
J*., Pemberton L*, Heyes M**, Evans L*, Penny R* and Cooper DA*. Centre for Immunology, St.
Vincent's Hospital, Sydney, Australia, **National Institute of Health, Bethesda, Maryland, USA and
Department of Medicine, University of California, San Diego, USA
Objectives: Quinolinic acid (QUIN), an excitotoxin acting through the N Methyl D Aspartate receptor, has been
found to be markedly elevated in the cerebrospinal fluid of patients with AIDS dementia complex (ADC), raising the
possibility of its importance in the pathogenesis of ADC. The cellular origin of QUIN and its relationship to HIV-1
infection and cytokines are unknown but at least one cytokine, gamma interferon, can "switch on" the first enzyme in
QUIN synthesis. We tested the hypothesis that HIV infected and activated macrophages could produce QUIN.
Methods: Human macrophages were isolated from peripheral blood mononuclear cells and grown in serum-free
conditions. The production of QUIN by resting macrophages was compared with the production by macrophages
infected with various strains of HIV-1 including those from patients with severe ADC. To substantiate that QUIN was
produced by the kynurenine pathway, [13C6]-tryptophan was added to the media and assay for [13C6]-QUIN was
undertaken by gas chromotography-mass spectrometry. Next, macrophages were activated by gamma interferon and
QUIN assayed. Lastly, two populations of macrophages were infected one with cytomegalovirus (CMV) and the other
with human herpes virus type 6 (HHV-6). Supernatants for QUIN analysis were taken at 24, 36,48 and 60 hours.
Results: Resting macrophages did not produce QUIN. HIV-1 infected macrophages produced up to 20,000 nM of
QUIN and there was no significant difference in QUIN production by HIV-1 isolated from patients with ADC versus
those without [13C6]-QUIN was detected in the supernatants from macrophages that had had [13C6]-tryptophan added
to the medium. Gamma interferon activated macrophages produced concentrations of QUIN similar to those infected
with HIV-1. QUIN production by HHV-6 infected macrophages peaked at 900 nM and CMV infected macrophages had
negligible production.
Conclusions: QUIN is produced by macrophages that have been infected by HIV-1, by macrophages activated by
gamma interferon andby macrophages infected with HHV-6. There is, however, differential production with the highest
levels resulting from infection with HIV-1 and gamma interferon activation. HIV-1 infected macrophages produce
QUIN in concentrations that are far in excess of the known several hundred-fold nanomolar neurotoxic concentrations.
The mechanism at least in part is probably related to gamma interferon production by inflammatory cells. These results
further support a role for QUIN in the pathogenesis of AIDS dementia complex.

Dr. Walter Royal, III, Johns Hopkins Hospital, Meyer 6-119, 600 North Wolfe Street
Baltimore, MD 21205 USA; Tel: [phone], Fax: [phone]

Bruce Jrres Brew, Centre for Inmunology, St. Vincent's Hospital,
Victoria Street, Sydney NSW 2010.
Phone: [phone] Fax: [phone]

ThB 1 512 Progressive Multifocal Leukoencephalopathy: Disease Progression, Stabilization
and Response to Intrathecal ARA-C in 26 Patients.
Britton, C.B., Romagnoli, M., Sisti, M., Powers, J.M.
Columbia University, New York, New York. U.S.A.
We evaluated twenty-six patients with progressive multifocal leukoencephalopathy (PML)
and HIV infection. Thirteen patients were treated with intrathecal cytosine arabinoside (ara-C).
Patient Characteristics and Treatment Criteria: Twenty-five men and one woman were referred for evaluation of
possible PML over a four year period. Twenty-thee men were homosexual, two heterosexual, one a former
parenteral drug user and the other, hemophiliac. The woman had a history of non-parenteral drug use. The age
range was 30 to 65, mean 43. In twenty-one patients, the diagnosis of PML was confirmed by brain biopsy,
including all thirteen patients treated with ara-C. The criteria for intrathecal ara-C treatment were clinical and
radiographic evidence of disease progression despite maximal tolerated anti-retroviral therapy with AZT or ddl.
Patient Outcome: Three patient groups were analyzed:
I. Rapid Disease Progression: Of four men in this category, two met criteria for AIDS because of recent PCP.
PML was confirmed by biopsy in three. CT and MRI showed unifocal disease in 3, multifocal in 1. Mean CD4
count was 50, range 16 to 92. All were taking AZT. Duration of illness to death was 4 to 5 months.
II. Disease Stabilization: Of nine patients in this category, one met criteria for AIDS because of recent PCP and
another had systemic tuberculosis two years prior. In seven patients, PML was the AIDS defining illness. PML
was confirmed by biopsy in five patients. CT and/or MRI showed multifocal disease in 4, unifocal in 5. Mean CD4
count was 238, range 30 to 800. Two patients stabilized without treatment, five on AZT and two when changed to
ddI.
III. Cytosine Arabinoside Treatment: Of thirteen treated patients (12 men and 1 woman), nine met criteria for AIDIS
because of PCP or KS and in four, PML was the AIDS defining illness. All received the drug intrathecally. Mean
CD4 count was 106, range 7 to 690, less than 50 in ten patients. Eight patients stabilized and improved, four for 7
months to 2 years; and four for 6 weeks to 6 months. Non-responders had large lesion size, major deficits or
brainstem disease. Survival times were greater in ara-C responders.
Conclusion: PML may stabilize in patients with CD4 counts > 200, either spontaneously or with anti-retroviral
treatment. Those with AZT-resistance may stabilize on ddl even with CD4 counts of 50 to 100. Disease
progression is most likely with CD4 counts <50, even with anti-retroviral treatment. An ara-C treated group, most
of whom had CD4 <50, had a 60 % response rate, sustained in half up to 2 years, transient in half up to 6 months.
Carolyn B. Britton, M.D. Phone: [phone]
710 W. 168th Street
New York, NY 10032 USA Fax: (212) 305-4578
New York, NY 10032 USA

ThB 1513 COMPARISON OF NEUROPSYCHOLOGIC
S 1PERFORMANCE BETWEEN AIDS-FREE IV DRUG USERS AND OMOSEXUAL
MEN. Concha., Mauricio, Selnes OA, Royal W, Updike M, NanceSproson T, Vlahov D, Palenicek J, McArthur JC. Johns Hopkins
Medical Institutions, Baltimore, MD USA
Objective: To compare the neuropsychologic performance between AIDS-free IV drug
users and homosexual/bisexual men according to HIV serostatus and CD4* count.
Methods: Baseline neuropsychologic performance of 107 IV drug users and 230
homosexual/bisexual men was compared. Tests measured attention, memory, and
psychomotor speed. Using multiple regression modeling, the analysis adjusted for
age, IQ score, race, six month history of alcohol use, cocaine, opiates and
arijuana. Subjects were stratified as seronegatives or seropositives with CD4'
cells a350 or <350/mm3.
Results: Among IV drug users and homosexual men the mean age (SD) was 34.8 (6.1) and
37.2 (7.2), median IQ score 83 and 109.5, and 102/107 (95.3%) and 42/230 (18.3%)
were non-white, respectively. IV drug users showed significantly poorer scores in
all tests in the univariate analysis. However, once adjusted for age, IQ and race
only Symbol Digit remained significant, and the Rey Complex Figure and Grooved
Pegboard tests borderline significant. IQ score was highly associated with
performance in all tests (p<0.001), except Grooved Pegboard (0.01<p<0.05). Except
for Rey Complex Figure-copy and Digit Span, higher age was associated with worse
performance on all tests (p<0.001). No significant interactions were observed
between risk group and the three strata.
Conclusions: These data indicate that age and IQ rather than risk group account
primarily for the differences in neuropsychologic performance, regardless of
serostatus and CD4~ count. Additionally, adjustment of neuropsychologic scores by
IQ may be a better correction for premorbid differences than years of education.
Dr. Mauricio Concha, Johns Hopkins Hospital, Meyer 6-181, 600 N.
Wolfe St. Baltimore, MD 21205 USA, tel: [phone]; fax: [phone]

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