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

6 Abstracts WePpA2086-WePpA2090

XIV International AIDS Conference

WePpA2086I Evidences of aborted HIV-1 infections among drug
users in northern Thailand
T. Hamano1, P. Sawanpanyalert2, H. Yanai3, K. Matsuo1, S. Piyaworawong4,
A. Kimura, S. Sapsutthipas1, J. Promjail, T. Hara6, S. Yamazaki6,
P. Warachit7, M. Honda6. IJSTAIDS Vaccine Project, JSTAIDS Vaccine
Project, C/O National Institute of Health, MOPH, 88/7 Sol Bamrasnaradura,
Tivanond Road, Nonthaburi 11000, Thailand; 2National Institute of Health,
Nonthaburi, Thailand; 3 TB/HIV project, Chiang Rai, Thailand; 4Mae Chan
Hospital, Chiang Rai, Thailand; 5 Tokyo Medical and Dental University Tokyo,
Japan; 6National Institute of Infectious Diseases, Tokyo, Japan; 7Ministry of
Public Health, Nonthaburi, Thailand
Background: There are evidences that certain individuals are resistant to human
immunodeficiency virus type 1 (HIV-1) and remain seronegative despite repeated
exposures. Drug users (DU) are usually exposed to HIV repeatedly. It is theoretically possible to detect traces of HIV genome in resistant DU who remain HIV
seronegative. We determine whether such evidences can be obtained from DU
followed up in a hospital in northern Thailand.
Methods: During 1999 and 2001, a cohort of 312 HIV-1 seronegative DU was
established and followed up every 4 months. The DU were tested for HIV antibody with Western blot confirmation, HIV-1 PCR, and CD4 and CD8 cell counts.
A random subset of the DU was also measured for cytotoxic T lymphocytes (CTL)
activities by cytokine ELISPOT assay.
Results: We could amplify gag genomes in 16 DU (gag positive). Fifteen of the
16 DU (equal to 5.13% of the total HIV-1 seronegative DU in the cohort) did not
seroconvert to HIV-1, even with Western blot assay. Only one of the gag positive
DU seroconverted to HIV-1. Out of the 14 DU, we could successfully sequence
gag genes and found that the genes were highly homogeneous in comparison
with gag genes of HIV-1 positive individuals in the area. Furthermore, several gag
positive DU have CTL activity to gag region. This suggests that they have ever
been infected with HIV-1 and could eliminate virus from their body by genetic
and/or immunological reasons.
Conclusions: We documented DU with HIV-1 genome without seroconversion.
This would provide evidences for aborted HIV-1 infections in this repeatedly exposed population.
Presenting author: Takaichi Hamano, JST AIDS Vaccine Project, C/O National
Institute of Health, MOPH, 88/7 Soi Bamrasnaradura, Tivanond Road, Nonthaburi
11000, Thailand, Tel.: [phone], Fax: [phone], E-mail: hamano
@dmsc.moph.go.th
WePpA2087 Chronic immune activation caused by HIV-1
infection results in impaired signal transduction
and anergy
Q. Leng, G. Borkow, A. Kalinkovich, Z. Bentwich. R.Ben-Ari Institute of Clinical
Immunology and AIDS Center, Kaplan Medical Center, Hebrew University
Hadassah Medical School, Rehovot, Israel
Background: We have previously suggested that chronic immune activation by
HIV is a major factor in the pathogenesis AIDS. Such activation contributes to
CD4 T cell decline, persistent HIV replication and impaired immune responses.
Methods: To further address this issue, we studied the immune profile and signal
transduction of cells obtained from highly immune activated and non activated,
HIV-1 infected individuals.
Results: The highly immune activated individuals in comparison to the non activated ones, had i) significantly higher expression of known activation markers
(HLADR, CD38) as well as of the cytotoxic T lymphocyte-associated antigen 4
(CTLA-4) and concomitant lower CD28 membrane expression; ii) higher cellular
levels of the adaptor suppressive protein Cbl-b; iii) absent or attenuated phosphorylation of Extracellular signal-Regulated 1/2 (ERK1 and ERK2); iv) reduced cell
proliferation to recall antigen and to anti CD3 stimulation.
Conclusions: 1) These findings are similar to those we reported in chronic
immune acitivation caused by persistent helminth infection (Borkow et al., JCI
106:1053;2000). 2) Chronic immune activation has a major suppressive impact
on the immune response and on signal transduction. 3) Suppression of the immune activation present novel approaches to the therapy of HIV-1.
Presenting author: Alexander Kalinkovich, AIDS Center, Kaplan Hospital, Rehovot 76100, Israel, Tel.: [phone], Fax: [phone], E-mail: alex_k
@clalit.org.il
WePpA2088 B7-H1 is upregulated in HIV infection and is a
I I valuable novel surrogate marker of disease
progression
D. Trabattoni, M. Saresella2, M. Biasin3, G. Maffeis3, A. Boasso1, H. Dong4,
L. Chen4, M. Clerici5. 'Chair of Immunology Milano, Italy; 2IRCCS Don
Gnocchi, Milan, Italy; 3 Chair of Immunology Milan, Italy; 4 Dept Immnunol, Mayo

Clinic, Rochester, United States; 5Chair of Immunology Univ Milano, Milano, Italy
Background: B7-H1 is a member of the B7 family that does not interact with
CD28, CTLA-4 or ICOS. Ligation of B7-H1 to a putative T cell receptor results in
the preferential production of IL-10. Because IL-10 is increased in HIV infection,
we investigated if B7-H1 would be upregulated in HIV-infected individuals.
Methods: The expression of B7-1, B7-2, and B7-H1 on CD3, CD14, and CD19
resting and stimulated cells was evaluated using a specific B7-H1 mAb and

mRNA was quantified by PCR in PBMC of 44 HIV-infected HAART-treated patients (HIV) and of 10 controls (HC). IL-10 production and mRNA was quantified
as well.
Results: IL-10 was significantly increased in HIV compared to HC. B7-H1 expression was augmented on resting (p=.02) and LPS-stimulated (p=.005) CD14+ and
CD19+ + (resting: p=.01; stimulated:p=.002) cells of HIV. B7-H1-specific mRNA
was similarly augmented in resting and in anti-CD3/CD28 antibody- stimulated
HIV PBMC (resting: p=.04; stimulated: p=.03). B7-H1 was upregulated on CD3+
(resting: p=.006; stimulated: p=.01); CD14+ (stimulated: p=.03) and CD19+ (resting: p=.006; stimulated: p=.005) cells of HIV patients with lower CD4 counts
(>400/ml). Analogously, B7-H1 was increased in CD3+ (resting: p=.04); CD14+
(resting: p=. 04; stimulated: p=0.03) and CD19+ (stimulated: p=0.02) cells of patients with detectable viremia (< 2,000 copies HIV RNA/ml). These differences
were confirmed by quantification of receptor-specific mRNA. The B7-H1/B7-1
mRNA ratio in unstimulated PBMC was 0.82 in HC and 2.3 in HIV patients; the
B7-H1/B7-2 ratio was 0.51 in HC and 5.1 in HIV. Similar ratios were seen in activated PBMC.
Conclusions: B7-H1 is upregulated in HIV infection; the degree of dysregulation correlates with clinical severity of the disease. This finding could explain the
increase of IL-10 production seen in this disease. Antigen presentation by B7-H1 -overexpressing and IL-10-producing APC could be responsible for tolerance and
active evasion of protective immunity.
Presenting author: Mario Clerici, Chair of Immunology, Disp Lita Vialba, Via GB
Grassi 74, 20129 Milano, Italy, Tel.: [phone], Fax: [phone],
E-mail: mago @ mailserver.unimi.it
WePpA2089 Association between an interleukine-4 promoter
polymorphism and the acquisition of
syncytium-inducing (SI) human immunodeficiency
virus type 1 variants
D. Kwa, R.P. van Rij, B. Boeser-Nunnink, J. Vingerhoed, H. Schuitemaker. CLB -
Sanquin, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands
Background: The acquisition of syncytium inducing (SI) coreceptor CXCR4 using (X4) HIV-1 variants is associated with poor prognosis and a more rapid disease progression. SI/X4 HIV-1 emerge only in 50% of the HIV-1 infected individuals. The underlying mechanism for the appearance of SI/X4 is still poorly understood. It has been suggested that a strong T-helper 2 response might influence
the acquisition rate of SI/X4 HIV-1 variants. A C-to-T polymorphism at position -
589 upstream of the open reading frame of the IL-4 gene has been reported. In a
cross sectional study in HIV-1 infected Japanese individuals, this IL-4 -589T allele
was associated with an increased frequency of SI/X4 HIV-1 (Nakayama, E.E. et
al, J Virol 2000;74:5452-5459.).
Methods: We performed a retrospective longitudinal study on HIV-1 disease
progression and the acquisition of SI/X4 HIV-1 variants in relation to the IL-4 -
589 polymorphism in HIV-1 infected individuals of the Amsterdam Cohort Study
(n=364). All these cohort participants have a documented or very accurately estimated date of seroconversion for HIV antibodies and for SI/X4 conversion.
Results: Comparing individuals with a wild-type -589 C/C genotype with C/T heterozygotes and/or T/T homozygotes, we found no effect of the -589C-to-T polymorphism on progression to AIDS (Relative Hazard [RH] 0.94; P=0.71 for IL4
- 589 C/T combined with T/T in comparison to wild-type) or survival (RH IL4 -
589 C/T or T/T, 0.70; P=0.94). In contrast to the previously reported study, we
found that the -589C-to-T polymorphism was associated with delayed acquisition of SI variants (RH, 0.58; P=0.03 for IL4 -589 C/T or T/T to wild-type). After
the emergence of SI/X4 HIV-1, we observed a trend towards a more accelerated
progression to AIDS for carriers of the -589T allele.
Conclusion: In our study group the IL4 -589T allele was associated with a delayed acquisition of SI/X4 variants and did not affect overall disease progression.
Presenting author: David Kwa, Plesmanlaan 125, 1066 CX, Amsterdam, The
Netherlands, Tel.: [phone], Fax: [phone], E-mail: Dkwa@CLB.
ni
WePpA2090 Biological phenotype of recombinants and non-B
HIV primary isolates from Spanish patients
L. Perez-Alvarez', E. Delgado1, M.L. Villahermosa', M.T. Cuevas',
R. Carmona', E. Vazquez de Parga', L. Medrano', M.M. Thomson1,
L. Cuevas', M. Sierra1, A. Prieto2, R. Rodriguez3, M.J. Lopez-Alvarez4, R. Ojea
de Castro5, R. Najera. iArea de Patogenia Viral, CNBF, Instituto de Salud
Carlos IIlL Madrid, Spain; 2 H. Xeral de Galicia. Santiago de Compostelasa, La
Coruna, Spain; 3H. Santa Maria Madre, Orense, Spain; 4H. Xeral Calde, Lugo,
Spain; 5Complejo Hospitalario, Pontevedra, Spain
Background: To study the biological phenotype and amino acid changes in V3
of recombinants and non-B HIV isolates from Galicia.
Patients: 40 patients, diagnosed between 1999-2001, infected with different re
combinants and non-B HIV subtypes. 72.5% were Spanish. Transmission route:
IDU(60.6%), HT(36.8%), HO(2.6%).
Methods: pol and V3 regions were amplified and sequenced. Phylogenetic analysis were performed using Clustal W, Treeview, Chromas, Seqman and Simplot. Primary isolates were obtained by coculture of PBMCs from patients and
from healthy donors. SI phenotype was studied in MT2. Coreceptor use (CCR1,
CCR2b, CCR3, CCR5, CXCR4, BOB, BONZO) and tropism was evaluated in