Programme Supplement [International Conference on AIDS (16th: 2006: Toronto, Canada)]

Late Breaker Abstracts:,,,: Uk' s T H L B 0 301..}h HIV neutralizing IgA in the genital tract of high-risk Kenyan
sex workers is prospectively associated with protection
against sexual acquisition of HIV
T T. Hirbod', R. Kaul2t, C. Reichard', J. Kimani, E. Ngugi3, J. Bwayo3,
N. Nagelkerke4, S. Moses4, K. MacDonald', K. Broliden', The Kibera
t. HIV Study Group. 'Karolinska Institutet, Stockholm, Sweden,
University of Toronto, Toronto, Canada, University of Nairobi,
Nairobi, Kenya, 4University of Manitoba, Winnipeg, Canada, sMount
SSinai Hospital, Toronto, Canada
Background: HIV-neutralizing IgA has been described in the blood
Fxx and genital tract of highly-exposed, persistently seronegative
' (HEPS) individuals, but well controlled studies have not been
E performed. We performed a prospective, nested case control
study to examine the association of HIV-neutralizing genital tract
t. IgA with HIV protection in high-risk female sex workers (FSWs).
Methods: A randomized trial of monthly antibiotic prophylaxis
to prevent STD/HIV infection was performed from 1998-2002,
$:* in HIV-uninfected Kenyan FSWs. Cervicovaginal secretions were
'c collected and stored at enrolment. After trial completion, FSWs
who acquired HIV were matched 1:4 with uninfected controls. IgA
was purified from cervico-vaginal secretions, and its ability to
neutralize clade A and C primary HIV isolates was assayed using a
pre-established protocol. Immune assays were performed off-site
Late Breaker by investigators blinded to clinical outcome.
Abstracts Results: Twenty-four FSWs who acquired HIV were matched
with 89 controls based on sexual risk taking and time of cohort
enrolment. Clade A HIV neutralizing IgA at enrolment was. associated with protection against HIV acquisition (P=0.03), and
there was a trend to protection with clade C neutralizing IgA
(P=0.1). HSV-2 infection was associated with HIV acquisition and
with a trend to reduced neutralizing IgA.
Conclusions: HIV-neutralizing IgA in the genital tract of highrisk Kenyan FSWs, as assayed by blinded investigators using a
pre-defined protocol, was associated with subsequent protection
against sexual HIV acquisition. The induction of HIV-neutralizing
mucosal IgA may be an important goal for HIV vaccines.
THLBO302
U Preservation of a subset of SIV-specific CD4+ T cells with
central memory markers correlates to control of viremia in
SIVmac251 infected macaques
von Gegerfelt A.', Valentin A.', Patel V.', Rosati M.', Alicea C.',
Morrow M.', Felber B.', Paviakis G.I. 'National Cancer Institute at
Frederick, Center for Cancer Research, Frederick, United States
Background: The identification of immune responses responsible
for control of HIV/SIV replication, correlating with the prevention of
progression towards AIDS is critical for the design of prophylactic
and therapeutic vaccines against HIV infection.
Methods: We study 3 cohorts of chronically SIV-infected
macaques controlling viral replication. Macaques infected by the
non-pathogenic Rev-independent SIV strain control viremia for up
to 7 years (group 1). Macaques infected by the attenuated SIV
which were subsequently challenged with pathogenic SIVmac251
(group 2) and continue to control viremia for more than 4 years (VL
<1000-100,000 copies/ml). SIV infected macaques treated with a
combination of antiviral drugs (ART) for 20 weeks, and immunized
with optimized forms of DNA vectors expressing modified forms
of SIV antigens (group 3). Macaques receiving DNA showed
a significant decrease in viral load after therapy termination
compared to controls (p<0.001). Some animals (6/12) continue
to control viremia (levels <100-10,000 copies/ml) for more than
2 years. Their cellular immune responses were boosted by DNA
vaccination and persisted despite lower virus loads.
Results: The animals of these 3 groups were monitored for plasma
viremia and the presence of SIV specific T-cell memory subsets
using intracellular staining and 10-parameters flow cytometry.

Flow cytometric analysis of PBMC revealed preservation of central
memory T cells, defined as CD3+ CD45RA- CD28+ in the 3 cohorts
of 'controllers'. We also found that a subset of SIV-specific central
memory CD4+ cells was preserved in all the macaques with
significant control of viremia, whereas this population was absent
in macaques with progressive disease.
Conclusions: Our results demonstrate that preservation of SIVspecific CD4+IFNgamma+ central memory T cells in SIV infected
macaques correlate with control of viremia and lack of progression
towards immunodeficiency. Animals with progressive disease
had increased CD8+T cell responses with effector memory (EM)
phenotype.
THLBO303
CXCR4-utilizing HIV-1 strains activate innate immunity via
CD14 and toll-like receptor 2
H. Zhu', R.C. Huard', M. Nociaril, T. He', K. Zerrial, Z. Chen2, D.
Golenbock3, J.L. Ho', AIDS pathogenesis, Immunology, innate
immunity. 'Joan and Sanford I. Weill Medical College of Cornell
University, Medicine Div International Medicine & Infectious
Diseases, New York, NY, United States, 2Aaron Diamond AIDS
Research Center, The Rockefeller University, New York, NY, United
States, 'University of Massachusetts Medical School, Medicine, Div
Infectious Diseases, Worcester, MA, United States
Background: Exactly how HIV-1 infection leads to AIDS remains a
fundamental poorly answered scientific question. Since generalized
immune hyperactivation and rising serum proinflammatory
cytokine levels predict HIV-1 disease progression to AIDS, and
Toll-like receptors (TLRs) mediate innate immune inflammatory
responses, studies were conducted to evaluate HIV-1 interactions
with TLRs. We report novel findings and a previously undiscovered
potential mechanism for AIDS pathogenesis in that late-stage
CXCR4-utilizing HIV-1 strains activate innate immune cells via Tolllike receptor (TLR)-2.
Methods & results: TLR-expressing reporter cell lines were used
to show that late-stage CXCR4 (X4)-utilizing HIV-1 strains transduce
intracellular signals via human TLR2. X4 HIV-1 also stimulated proand anti-inflammatory cytokine production from human monocytes
and/or macrophage-like cell lines in a CD14- and TLR2-dependent
manner and did not require CD4 or CXCR4 chemokine receptor
interaction. These effects were seen not only with laboratory cloned
HIV-1 but also with clinical isolates of B and C clades. However,
monocyte and TLR2 reporter cell line activation was not seen when
CCR5 monotropic HIV-1 strains were evaluated. These effects were
mediated by intact HIV-1 particles as shown by studies using several
antibodies. Moreover, experiments with several HIV-1 molecular
constructs indicated that a critical component mediating TLR2
activation is genetically encoded by the virus, but is an element(s)
other than the gpl20 envelope glycoprotein. At present, the viral
encoded or viral associated ligand(s) responsible for TLR2 mediated
innate immune cell activation remains to be identified.
Conclusions: Overall, these data uncover a new mechanism
through which HIV-1 may disturb normal immune function
and prompt the immune collapse and other associated clinical
pathologies of AIDS. The lack of TLR2 activation by CCR5-utilizing
HIV-1 strain and failure to trigger a pro-inflammatory response
may also be a measure of immune evasion in early-stage viruses
allowing infection by these strains via the mucosal route.
THLB0304
Proteo-liposomes as a new drug delivery system to HIV
reservoir cells and free virion entrapment
T. Bronshtein', S. Pollack', M. Machluf'. 'TECHNION- Israel Institute
of Technology, Biotechnology and Food Engineering, Technion
City, Haifa, Israel, 'TECHNION - Israel Institute of Technology,
Immunology Department, Bruce Rapport Medical School, Technion
City, Haifa, Israel
Background: To date all existing ART's focuses on prolonging the

latent asymptomatic phase of HIV/AIDS by the inhibition of viral

XVI INTERNATIONAL AIDS CONFERENCE * 13-18 AUGUST 2006 * TORONTO CANADA * PROGRAMME SUPPLEMENT