Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Track B: Clinical Science

Mo.B.1318 - Mo.B.1322

Conclusions: Serum vitamin A levels increased over time in the IVIG treatment group.
Overall mortality was not consistently associated with initial levels or subsequent changes in
Vitamin A.
J.S. Read, PAMA - CRMC - NICHD, 6100 Executive Boulevard Room 4B IF, National
Institutes of Health, Bethesda, MD 20892, USA.Telephone: (301) '196-7339;
Fax: [phone]; email: ReadJ@hd0 I.nichd.nih.gov
Mo.B.1318
DETECTION OF FUNGAL ORGANISMS IN WHOLE UNSTIMULATED SALIVA BY
CYTOLOGIC ANALYSIS IN PEDIATRIC HIV INFECTION
Hicks John.*, Flaitz CM**, Carter B*, Rossmann 5**, Simon C*, Cron S*,Webb W*, Shearer
WT*, Kline MW*. *Baylor Oral Manifestations of Pediatric HIV Study Gp, Baylor CoIl Med,
Tx Children's Hosp; **UnivTx-Dental Br, Houston,TX
Objective: To determine by cytologic examination the prevalence of fungal organisms in
whole unstimulated saliva from children with vertically acquired IIV infection, and to compare cytologic results with clinical and laboratory data.
Methods: Thirty-eight children with vertical exposure to HIV were included in the study
and categorized as follows: Group I (GpI) Symptomatic HIV-infected; Group 2a (Gp2a)
=- Asymptomatic HIV -infected; and Group 2b (Gp2b)= HIV -exposed, but uninfected.
Whole unstimulated saliva was obtained for cytologic evaluation (H&E and MSN/silver
stains of cytospin and cell block preparations). Selected samples were evaluated by transmission electron microscopy
Results: Fungal organisms were identified cytologically in 22% of Gp I, I 1% of Gp 2a and
9% of Gp 2b. Antiretrovirals were taken by 93% of HIV-infected children, and 20% of these
individuals had fungi present. Fungi were not found in those not taking antiretrovirals. Fungi
were more commonly seen in HIV-infected children (25% vs 9%) not receiving antiviral,
antibacterial, and antifungal medications. Fungal organisms were found more frequently in
HIV-infection (Gpt, Gp2a) with low CD4 percentages. Children with CD4% above 25%
showed no fungal organisms.Those with CD4% between 15 to 24% and < 15% had fungi in
28 and 30% of cases, respectively. Analysis by immunologic categories in HIV-infected children showed that fungi were not present in those without evidence of suppression. Fungi
were seen in 18% and 27% of HIV-infected children with moderate and severe immunologic suppression, respectively.
Conclusions: Fungal organisms in whole unstimulated saliva are more prevalent in HIVinfected children than HIV-uninfected children. Symptomatic HIV-infected children have a
higher likelihood of having fungal organisms within their saliva.With increasing immunologic
suppression and decreasing CD4 percentage, the proportion of children with saliva containing fungi increases. Presence of fungal organisms may represent oral carriage and/or mucosal colonization and may influence the occurrence of oral or systemic candidiasis in these
immunocompromnised children.
John Hicks. Dept of Pathology MC 1-2261,Texas Children's Hosp, 662 I Fannin St, Houston,
TX 77030.Tel: 713-770- I 869; Fax [phone]; E-mail: [email protected]
Mo.B. 1319
CHANGES IN IL- 12 PRODUCTION IN A PHASE I/I1 STUDY OF THE PROTEASE
INHIBITOR INDINAVIR (MK-0639) OF HIV-INFECTED CHILDREN.
Chougnet. Claire, KR Fowke, BU Mueller, S Smith, P Deutsch*, PA Pizzo, GM Shearer.
National Cancer Institute, Bethesda, MD; * Merck Research Laboratories, Rahway, NJ, USA
Objective: IL-12 is a powerful inducer of type I responses and plays a central role in resistance to intracellular pathogens. Its production is impaired in HIV-infeted patients, even at
early stages of the infection. Our objective was to assess the effect of protease inhibitor
indinavir treatment on IL-12 produin i ction in HIV-infected children.
Methods: HIV-infected children were enrolled in a dose escalation Phase I/I study of indinavir (see abstract of BU Mueller for clinical details). Major immunologic parameters were
CD4 counts and IL-12 and IL-o0 production by PBMC stimulated with S. aureus Cowan.
Changes in CD4 count were examined for correlation with changes in IL- 12 production.
Additional ongoing studies are evaluating other markers of immune status.
Results: Eighteen children have been studied thus far at low doses: 9 received 250 mg/m2
and were followed for 12 wk; and 9 received 350 mg/m2 and were followed for 2 wk. In
the 12 wk group, marked increases in IL- 12 production appeared to parallel substantial
increases in CD4 count. Of the 9 patients, 5 exhibited >50% increase in CD4 count. Of
those 5 patients, 4 exhibited >4-fold increase in IL- 12 production. In contrast, the 4 children
who exhibited less than a 50% increase in CD4 counts had no increase at all in IL- 12 production. In the 2 wk group, 4 children had >50% fold increase in CD4 counts even after
this short duration. Of these 4 patients, 3 exhibited >4-fold increased IL-12 production. In
addition, 2 of 5 patients without 50% increase in CD4 counts had increased IL-I 2 (>4-fold).
Increased IL- I 2 generally paralleled decreased IL-10 production. In preliminary analyses, 6 of
7 patients evaluated at wk I 2 have evidence of decreased apoptotic cell death, and 5 of
those have >50% increases in CD4 counts. Results are being further analyzed forT helper
cell function.
Conclusions: In this preliminary study of children treated with low, likely suboptimal, doses
of indinavir we observed parallels of increased CD4 counts with increased IL-12, especially
at wk I 2.The reduction in viral load (see abstract of BU Mueller) resulting from protease
inhibitor therapy may have contributed to the observed changes in cytokine production.
These preliminary data suggest that assessment of immune function, especially of IL- I 2 production, in addition to CD4 counts, may be important in anti-viral therapeutic evaluation.
Claire Chougnet, National Cancer Institute, NIH, Bldg I0, Rm 4B I7, 9000 Rockville Pike,
Bethesda, MD 20892, USA; tel (30 I) 402-I1890, fax (30 I) 102-3613
Mo.B. 1320
CARDIAC DISEASE IN HIV-INFECTED CHILDREN AND ADOLESCENTS NEED FOR
EARLY DIAGNOSIS AND TREATMENT
Herberg, Ulrike I., Lehn M., GroW, Bialek R., Redel, D.A. University of Bonn, Bonn, Germany
Objective: To investigate the onset, natural course and treatment of cardiac disease in a
cohort of 56 HIV+ children and adolescents.
Design: 56 HIV+ patients were followed up by serial echocardiograms and ECG s between
1988 and 1996 (mean observation time: 2.6 years [0.5 - 6.5 years], mean number of

echocardiograms / patient: 3.6). A group of 50 healthy HIV- negative (HIV-) individuals was
examined as age-matched control.
Results: In the HIV+ cohort, signs of left ventricular (LV) dysfunction (reduced LV-contractility and / or LV-dilatation) was found in 38% vs. 3% in the HIV- control group (p < 0.001).
Pericardial effusion was shown in 15% (HIV+) vs. none (HIV-), mitral valve regurgitation in
9% (HIV+) vs. none (HIV-).
Despite severe LV-cardiomyopathy in 7 patients only 2 of them showed typical clinical signs
of congestive heart failure.
LV-cardiomyopathy was correlated significantly with progression of disease, stage (p < 0.001),
and CD4-cells < 100/pI (p < 0.001).
Treatment with digoxin and diuretics showed prolonged benefit for over more than 12
months only in patients with mean CD4-counts - I00/l; in seriously immunocompromised
children with severe cardiomyopathy, there was only short term efficacy
Isolated right ventricular dysfunction with primary pulmonary hypertension was seen in
only I HIV+ individual, whereas right ventricular enlargement was frequently recognized in
patients with Pneumocystis carinii pneumonia or other pulmonary disease.
Conclusions: Left ventricular dysfunction or cardiomyopathy is a fequent condition in HIVinfection and correlated with progression of disease and decrease of CD4-cells. Clinical
symptoms may be erroneously attributed to other organ systems or opportunistic infections and easily overlooked.
Serial echocardiography is recommended with CD4-cells < 200/qI or rapid progression of
disease even in asymptomatic patients to start necessary treatment without delay.
Ulrike I. Herberg, Univtersity of Bonn, Children's Hospital, Adenauerallee 119 53113 Bonn,
GermanyTelephone r49-228-2873333, Fax [phone]
Mo.B.1321
CRYPTOSPORIDIUM GASTROENTERITIS IN HIV INFECTED CHILDREN
de los Ma I, Garcia MaJ, Ramos JT, Martin P Hernandez T, Fortuny C, Beltran JM.
Pocheviche I and Spain Group of Pediatrics HIV Infected.
Objective: To determine the incidence, clinical, immunological and evolutive features of
Cryptosporidium gastroenteritis in HIV- I infected children.
Methods: 505 children infected either by haemoderivates or vertically with HIV, are restrospectively studied.Clinical features tested were anorexia,abdominal pain, malnutrition, number and characteristics of the stools and time of the diarrhoea onset before the diagnosis
was established analitical tests were directed in order to find esteatorrea, and CD4 count.
The evolution, treatment, collangitis and mortality ratio were evaluated.
Results: We have found 43 cases (8.5%) of gastroenteritis due to Cryptosporidium in children infected by HIV (7 I% perinatally acquired and 29 % by hemoderivates). Following the
CDC classification we found: B24 3, C, B3 5, C22,and C326 cases. 65% of the patients
had opportunistic infections previous to the diagnosis. Anorexia was present in 95%,
abdominal pain in 68% and malnutrition in 8 1% of the cases. Malabsortion was objetivated
in 73%, collangitis in 30% (in 10 cases of them associated to CMV) and CD 4 count level
was 200 46. Duration of diarrhoea previous to the diagnostic onset was 83 days (4 -300)
with a miedian of 7-8 stools per day (3-20). Only in 13% had stools with blood. Signs of
hepatic celular necrosis (ASAT and ALAT over 120 UIL) in 8 cases, and signs of collestasis
GGT > 80 U/L) in 18 cases. Nineteen per cent of cases (6/43) had an acute gastroenteritis,
that responded with to treatmentTwenty six per cent ( 1 1/43) had a long time favourable
evolution of cronic gastroenteritis. Fifty five per cent (24/43) died after a torpid evolution.
Conclusion: Cryptosporidiasis is a frequent opportunistic infection in severaly immunoincompetent HIV children and a lot of cases derive in malabsortion with important nutritional impairment and high mortality. Early diagnosis is desirable even though the lack of available therapies up to now.
Ma. I de Jos, Hospital Infantil La Paz, Paseo de la Castellana 261. 28046 Madrid, Spain
Mo.B. 1322
DISEASE PROGRESSION IN A COHORT OF HIV INFECTED INFANTS FOLLOWED
SINCE BIRTH:THE WOMEN AND INFANTS TRANSMISSION STUDY (WITS)
Daz. Clemente-I, Hanson IC2,Watson J3, Cooper ER4, Lew J5, Nugent R5, Mendez H6, Pitt
J7, Rich K8, Smeriglio V5 for WITS. I UPR, San Juan PR; 2Bayloc, Houston TX; 3NERI,
Watertown MASS; 4BU, Boston MASS; NIH, Bethesda MD; 6SUNNY, NYC NY;
7Columbia, NYC NY; 8U of Chicago IL; NIH ete n lan, Bethesda, Maryland, USA.
Objective: To characterize HIV disease progression in a large cohort of infants followed
prospectively since birth using the Centers for Disease Control (CDC) 1994 Revised
Classification for Children.
Methods: All clinical events prior to 4/1/95 in the HIV infected group of infants were
reviewed utilizing a study developed staging instrument based on the CDC Class. Absolute
CD4 counts and percents were performed at birth, I, 2, 4, 6 and every six mos. thereafter.
Frequencies of disease events,time to event curves and the probabilities at each age of
reaching Class A (mild), B (moderate), C (severe or AIDS defining); Immunologic Stage 2
(moderate) and 3 (severe); or death were calculated using the Kaplan-Meier method and
the Proportional Hazards Model.
Results; From December 1989 to April 1995 a total of 847 infants born to HIV infected
mothers were enrolled in WITS.There were 133 infants determined infected by study
defined criteria as of 5/3 1/95, with clinical events data available for I128 (median follow-up
24 mon.; range 1-61I).There were I16/I128 deaths, or a 12.5% mortality rate.The cumulative
probabilities from birth (not mutually exclusive) of entering Class A, B, and C or
Irmmunologic Stages 2 and 3, or death, are shown on the adjoining table. Median ages at
progression to Class A, B, and C were 5, I I, and 48 mon. respectively. Median duration in
Classes N, A, B, and C were 4, I I, I18, and 23 mon. respectively. Clinical Class B or worse
was reached by 56% of infants by 12 reS, of age. Entering Class A did not increase risk of
progression to Class B or C; but entering Class B or Immune Stage 3 was highly predictive
of incieased risk of progression to C (RR I 12.5,7.9; p -0.000 I). Most infants follow the
CDC Clans proposed sequence of Clinical Stages (N-A-B-C) with only 10% skipping Class
A, 2% skipping Class B and I% skipping Class C.

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