Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

24 Abstracts WePeA5789-WePeA5792

XIV International AIDS Conference

SWePeA5789 Plasma IL-12 levels in Mycobacterium tuberculosis
and HIV infected patients
FA. Post1, L.G. Bekker1, D. Wilson1, R. Wood1, G. Kaplan2. 1Infectious
Disease Unit, University of Cape Town Lung Institute, Infectious Diseases Unit,
UCT Lung Institute, PO Box 34560, Groote Schuur 7937, South Africa;
2Laboratory of Cellular Physiology and Immunology, The Rockefeller University
New York, United States
Introduction: A protective cellular immune response to Mycobacterium tuberculosis (MTB) infection is associated with the induction of a Thl cytokine response,
characterized by the production of interleukin-2 (IL-2), interferon-y (IFN-y), tumor necrosis factor-c (TNF-o) and IL-12. It has been suggested that impaired
IL-12 production may contribute to enhanced susceptibility to tuberculosis (TB) in
HIV+ve patients and development of more severe disease. We examined whether
TB patients with and without HIV co-infection and different manifestations of disease had different levels of Thl cytokines.
Methods: Patients with smear and/or culture positive TB were recruited from hospitals and clinics in Cape Town, South Africa. At the time of recruitment, patients
had received on average 8 days of TB therapy. HIV+ve patients had not received
anti-retroviral therapy. Patients were classified according to the extent of pulmonary involvement on X-ray. EDTA-blood samples were collected, and plasma
IL-12 (p40 and p70), IFN-y and TNF-u levels measured by ELISA.
Results: HIV-ve patients with initial TB and limited disease on chest radiograph
had elevated IL-12 levels compared to HIV-ve patients with more extensive disease or recurrent TB (p<0.0002). HIV+ve patients without TB had similar levels of
IL-12 as HIV-ve patients with limited TB disease, whereas HIV+ve TB patients had
significantly higher levels of IL-12 (p<0.002). TNF-o levels were highest in HIV-ve
patients with limited TB disease, whereas IFN-y levels were highest in HIV+ve patients with TB. These results suggest that in TB patients, less extensive disease
is associated with a better immune response. In addition, HIV infected patients
have high levels of IL-12.
Conclusion: IL-12 may be associated with the induction of a protective immune
response that limits extent of disease in MTB, but not HIV infected patients.
Presenting author: Frank Post, Infectious Diseases Unit, UCT Lung Institute,
PO Box 34560, Groote Schuur 7937, South Africa, Tel.: [phone], Fax:
[phone], E-mail: [email protected]
WePeA5790 Serum IgE levels and IL-4, IFN-y and IgE
production in HIV infection
S.S. Shah1, J.P. McGowan', P. Muck2, I. Rodicio3, S. Blum1, C.B. Small2.
'Bronx-Lebanon Hospital Center, Bronx-Lebanon Hospital Center, 1650 Grand
Concourse, 8th floor, Bronx, NY 10457, United States; 2New York Medical
College, Valhalla, NY, United States; 'New York Presbyterian Hospital, New
York, NY United States
Background: Serum IgE levels are increased in advanced HIV infection. Both
IFN-y (IFN-G) and IL-4 regulate serum IgE levels. IL-4, IFN-G and IgE production were measured to determine their association with serum IgE levels in HIV
infection.
Methods: 25 HIV+ patients from an outpatient clinic in the Bronx, NY and 13
HIV- controls were studied. Serum IgE levels were measured by FAST test. Lymphocyte phenotypes were analyzed on the FACS after staining with monoclonal
antibodies. IFN-G and IL-4 production were measured by ELISA after incubating
PBLs with and without ConA (10ml) and collecting supernatants. IgE production
(RIA) was measured by incubating PBLs with and without increasing concentrations of IL-4.
Results: 14 (56%) of 25 HIV+ subjects were male; 11 (44%) had a history of
IDU, 14 (56%) had AIDS. Serum IgE (IU/ml) was increased in HIV+ vs. HIV- (134
vs. 3, p < 0.001) with higher levels in AIDS (160 vs. 39, p = 0.002). Serum IgE
negatively correlated with CD4% (r = -0.34, p = 0.08). Spontaneous (21 vs. 2, p
< 0.001) and ConA stimulated (25 vs. 6, p < 0.001) IL-4 production (pg/mi) was
increased in HIV+ vs. HIV-. ConA stimulated IFN-G production was increased in
HIV+ subjects (420 vs. 45, p = 0.01). Spontaneous IgE production (pg/mi) was
increased in HIV+ vs. HIV- (108 vs. 12, p = 0.05). Spontaneous IgE production
correlated with serum IgE levels (r = 0.99, p = 0.0001).
Conclusions: Serum IgE is increased in HIV+ subjects and correlates with low
CD4%. Spontaneous IgE production is increased in HIV+ and is the only parameter that correlates with increased serum IgE levels. Spontaneous and stimulated
IL-4 and stimulated IFN-G production are also increased in HIV+, but have no
correlation with serum IgE levels. Other cytokines may be involved in stimulating
HIV+ cells to produce IgE. Further studies are necessary to determine the relationship between increased serum IgE levels and IL-4 and IgE production in HIV
infection.
Presenting author: Sanjiv Shah, Bronx-Lebanon Hospital Center, 1650 Grand
Concourse, 8th floor, Bronx, NY 10457, United States, Tel.: [phone], Fax:
[phone], E-mail: idshah @ yahoo.com

iWePeA5791 IHighly active antiretroviral therapy including high
dose abacavir reduces cerebrospinal fluid human
immunodeficiency virus (HIV) RNA and soluble
tumor necrosis factor II receptor in children with
HIV encephalopathy
J. Saavedra-Lozano1, S. Madison2, J.T Ramos3, S. Marco4, P. Ferrer4,
F Sanz3, M.I. de Jose5, M. Navarro6, P Martin-Fontelos7, C. Rodriguez3,
E. Lanier2, 0. Ramilo1. 'UT Southwestern Medical Center, Dallas, TX, United
States;2 GlaxoSmithKline, Research Triangle Park, NC, United States; Hospital
12 Octubre, Madrid, Spain; 4GlaxoSmithKline, Madrid, Spain; 5Hospital La Paz,
Madrid, Spain; 6Hospital Gregorio Maranon, Madrid, Spain; 7Hospital Carlos Ill,
Madrid, Spain
Background: The pathogenesis of human immunodeficiency virus (HIV) encephalopathy in children is poorly understood. This study was conducted in children with documented HIV encephalopathy who were treated with highly active antiretroviral therapy (HAART) including high dose (12 mg/kg/dose) abacavir
(ABC). Soluble Tumor Necrosis Factor receptor II (sTNFr II) has been found to
correlate with immune activation and it is elevated in cerebrospinal fluid (CSF) of
adults with HIV dementia.
Methods: HIV RNA (vRNA), CD4%, and sTNFr II were analyzed longitudinally in
CSF and plasma.
Results: Fourteen children were enrolled, and 9 completed 48 weeks of followup. Indices at baseline and week 48 were as follows:
Median plasma Median plasma Median CSF Median CSF
Indices Baseline Week 48 Baseline week 48
vRNA cps/ml 68,000 79 370 79
sTNFr II pg/ml 742 495 49 33
% CD4 27 33 - -
At baseline there were no significant correlations among the immunologic and virologic indices analyzed. At week 48, 79% of children had vRNA levels below the
limit of quantitation (<80 cps/ml) in both CSF and plasma, and there were significant inverse correlations between CD4% and both CSF vRNA (r=-0.75, p=0.04)
and CSF sTNFr II (r=-0.92, p=0.001). There was also a significant correlation
between CSF vRNA and CSF sTNFr II(r=0.9, p<0.001).
Conclusions: These results indicate that CSF vRNA declines as a consequence
of therapy with a parallel reduction in sTNFr suggesting a decrease in immune activation within the central nervous system and an overall improvement in immune
function as documented by the recovery of CD4%.
Presenting author: Jesus Saavedra, UT Southwestern Medical Center, 5323
Harry Hines Blvd, Pediatric Infectious Disease. F3.202, Dallas. Texas. 75390 -9063, United States, Tel.: [phone], Fax: [phone], E-mail: jesus.saavedra@ utsouthwestern.edu
WePeA5792 Serum levels of soluble tumor necrosis factor
(TNF) receptors correlate with the degree of
subcutaneous adipocyte apoptosis in HIV-infected
patients with lipodystrophy
R Domingo', S. Veloso2, F. Montero1, J. Sirvent3, X. Matias-Guiu1, J. Viald6s3,
C. Gutierrez 3, M.A. Sambeat1, C. Aguilar3, J. Peraire3, C. Richart3. 'Hospital
de St. Pau, Barcelona, Spain; 2Hospital Joan XXIII, Tarragon, Spain; 'Hospital
Joan XXIII, Tarragona, Spain
Background: Subcutaneous adipocyte apoptosis is known to occur in lipoatrophic areas of HIV-infected patients with lipodystrophy.
Aim of the study: to characterize the relationship between the degree of subcutaneous adipocyte apoptosis and the simultaneous plasmatic level of soluble
receptors for TNF
Patients and methods: Patients were enrolled in the study provided that they had
clinical characteristics of HIV-associated lipodystrophy. Subcutaneous adipocyte
apoptosis was detected by the TUNEL technique. Plasmatic levels of soluble TNF
receptors 1 and 2 was performed by using ELISA method. Statistical analyses
were performed with the StatViewTM statistical package.
Results: Fifty-three patients were studied. Eight patients had to be excluded of
the study because of technical problems with the biopsy specimens. There were
22 men and 23 women with a mean age of 45.1 + 12.5 years (range: 33-74
years). The median time on antiretroviral therapy was (mean 36.6 months, range:
12-66). No subcutaneous adipocyte apoptosis was detected in 14 patients, it was
focal in 13 patients, moderate in 6, and diffusse in 12. The relationship of degree
of apoptosis and levels of TNFR is shown in the following table:
Degree of apoptosis TNFR1 (ng/ml) TNFR2 (ng/ml)
Negative 1.8 (1.05) 6.8 (3.4)
Focal 1.7 (1.9) 5.4 (3.9)

Moderate 1.8(0.8) 5.7(2.2)
Diffuse 2.8(1.9) 9.1 (7.1)
Kruskal-Wallis for TNFR1 (p = 0.01), and for TNFR2 (p = 0.02).
Conclusions: Our results suggest an association between TNFR levels and
adipocyte apoptosis in HIV lipodystrophic patients. Thus, TNF may be implicated
in the pathogenesis of HIV-associateed lipodystrophy.