Program Supplement [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

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[LBPEA90041
Therapeutic immunization with an inactivated HIV-1
immunogen in naive patients initiating antiretroviral
treatment: final results of a phase II, double-blind, placebocontrolled study
Moreno, Santiago, Gonzdlez-Lahoz, Juan, Pdrez-Molina, Jose'
A, Pefia, Josd M, Rubio, Rafael, Podzamczer, Daniel, Clotet,
Ventura, Viciana, Pompeyo, Maradona, Josd A, Bldzquez,
Rosa, Barros, Carlos, Ocafia, Inmaculada, Quereda,
Carmen, Gatell, Josd M, Ferndndez-Cruz, Eduardo (Spain)
Background: To date, no clinical study has shown virological
efficacy of an HIV-1 therapeutic vaccine.
Methods: Multicenter, double-blind clinical trial in
asymptomatic, HIV-infected adults, with no prior antiretroviral
therapy and with CD4 counts between 300 and 700oo/mm3.
Subjects were randomised to receive an immunogen (Remune)
or placebo. All the patients began therapy with a 2 drug
regimen that could be switched to a fixed 3 drug regimen
according to predefined criteria. Primary efficacy endpoints
were virological and/or immunological failure.
Results: Among 243 patients enrolled, 118 and 121 were
followed in the Remune and IFA groups, respectively. A similar
proportion of patients in the two groups were switched to
HAART (51% Remune, 52% IFA) and had similar compliance. A
primary endpoint was reached in 85 (36%) subjects (30% in the
Remune and 41% in the placebo group). Cox analysis showed a
significant reduction in the risk of developing virological failure
in patients receiving the immunogen when controlling for
baseline viral load (RR 0.63, 95%CI o.41-o.97, p=o.o34), or for
baseline viral load and CD4 cell count strata (RR 0.62, 95%CI
0.40-0.95, p=0o.029). Of special note, the immunogen elicited
significantly higher levels of HIV-i gag/pol-specific CTL
precursors that correlated negatively with viral load (R=-o.58,
p<o.o5). None of the Remune-treated patients who developed
high levels of CTL precursors had virological failure (p
Conclusions:This study shows for the first time that the
addition of an HIV-1 immunogen to antiretroviral therapy
confers a beneficial effect on virological suppression, most
likely by enhancing specific antiviral immune responses.
Corresponding author: Moreno, Santiago, Servicio de
Enfermedades Infecciosas, Hospital Ram6n y Cajal, Ctra.
Colmenar, Km 9,1, Madrid, Spain,
Tel: [phone], Fax: [phone],
Email: [email protected]
[LBPEA90051
HLA-B locus alleles influence the risk of mother to child
transmission of HIV-1
Winchester, Robert', Pitt, Jane', Magder, Larry', Charurat,
Manhattan', Ott, Jurg', Landay, Alan', Read, Jennifer
S.', Shearer, William', Handelsman, Edward', Luzuriaga,
Katherine'., Hillyer, George2, Blattner, William,
('United States; 2Puerto Rico)
Background: While certain HLA-B alleles are associated with
the rate of HIV disease progression, their role in transmission
is not known.
Methods: To determine the association of HLA-B alleles with
maternal-infant transmission of HIV-i, 83 transmitting and 163
non-transmitting mother infant pairs in the WITS cohort were
matched for ethnicity and study site. DNA from cryopreserved
lymphocytes was used for sequence-based H LA-B allele
typing.

Results: The distribution of H LA-B alleles differed in cases and
controls. Transmitting women more likely had B*13o2 (p=.o2),
B*3501 (p=.ol) and B*35o3 (p=.o4). The association of B*3501
and transmission was highest among African-Americans (OR
8.8, p=.ol). HLA-B*5ool, found primarily in Hispanics, was
associated with increased transmission, p=.ol. B*35o01 was
associated with transmission in women with low (<lo,ooo
copies/ml) (OR 12.5, p=.02) but not high (>io,ooo copies/mi)
viral load. (OR 2.6 p=.24). Among women without B*35olor
B*35o3, (removed to eliminate confounding) B*53o1 was
associated with decreased transmission (OR 0.3, p=0o.025).
B*5ooi and B*4901 were marginally associated with increased
and decreased transmission respectively (p=.o71 and.06).
Protective alleles had stronger effect in conditions of high viral
load. Infant HLA-B alleles had no significant effect on
transmission.
Conclusions: The association of maternal B*35o1 with
transmission and B*53o1 with protection differs from the
associations reported for disease progression, suggesting the
two involve distinct mechanisms. The protective allele B*4901
differs from the risk allele B*5ool by the same 5 amino acids
that the protective allele B*53o1 differs from the risk allele
B*35ol. This five amino acid motif both encodes Bw4
specificity (the NK receptor ligand) and affects the F pocket
that binds the C terminus of the antigenic peptide (CD8
cytotoxic T cell antigen binding), suggesting roles for innate
and adaptive immunity in transmission.
Corresponding author: Pitt, Jane, Columbia University, 622 W
168th St., PHW 463, New York, NY 10032, United States,
Tel: [phone], Fax: +i 212 342 5202,
Email: [email protected]
[LBPEA90061
Noninfected dendritic cells can cross-present HIV antigens
from apoptotic infected CD4+ T lymphocytes
Maraih6n, Concepcidn, Cohen, William, Hosmalin, Anne
(France)
Background: CD8+ lymphocyte response is fundamental in
protection against HIV infection, in association with CD4
lymphocyte and antibody responses. Dendritic cells (DC) are
required for the activation of naive T lymphocytes, and thus
they have a central role in the induction of protective immune
responses during HIV infection. However, they are not
frequently infected themselves. They have developed specific
"cross-presentation" pathways that allow them to present
exogenous antigens that are not directly produced in their
cytosol, and this pathway is especially effective in the case of
antigens expressed in apoptotic cells. To our knowledge, it has
never been shown for HIV antigen presentation.
Methods: H IV-infected human lymphoblastoid CD4 T cells
were UV-irradiated to induce apoptosis and incubated with
monocyte-derived DC. Viral antigen presentation was detected
through IFN-gamma ELISPOT secretion functional assays using
CD8 T cell lines specific for different Class-I MHC-restricted HIV
epitopes.
Results: H IV gag, nef and reverse transcriptase epitopes were
presented specifically to CD8 T cell lines derived from infected
patients. The presentation was Class-I MHC dependent,
occured in the presence of AZT and required physical contact
between DC and apoptotic bodies, excluding soluble antigens
or DC infection as a source of antigens for presentation.
Conclusions: This presentation pathway could be particularly
relevant in HIV infection, which induces death and apoptosis of
XIV International AIDS Conference BARCELONA - JULY 7-12

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