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

nodes, bone marrow, and in mature and naive CD4+ and CD8+
cells, up to 3 years post-infusion. Gene presence in naive
thymocytes was observed in patients with viremia up to
22,628 copies/mi. Compared to control construct-containing
T-cells, significantly longer survival was seen for RRz2 -containing T-cells. No preferential survival was observed for
RRz2-containing CD4- cells.
Conclusions: These findings demonstrate that de novo T-cell
development can occur from genetically engineered
hematopoietic progenitors in adult HIV-infected patients. This,
together with the preferential survival of ribozyme-containing
T-lymphocytes, supports the concept of gene therapy as a
modality to effect immune reconstitution. A phase II trial to
assess efficacy has been developed.
Corresponding author: Amado, Rafael, UCLA School of
Medicine, Division of Hematology/Oncology, 11-964 Factor
Bldg, Los Angeles, California 90095, United States,
Tel: [phone], Fax: [phone],
Email: [email protected]
LBOR11
Safety, immunogenicity and antiviral efficacy of a new topical
DNA vaccine in macaques with chronic infection and AIDS
Lisziewicz, Julianna, Xu, lianqing, Lewis, Mark, Trocio,
Jeffrey, Whitman, Lucia, Lori, Franco (United States)
Background: Several studies have demonstrated that vigorous
HIV-specific T cell immune responses can suppress virus replication
and eliminate HIV-infected cells. These findings provided the
rationale for the development of therapeutic vaccines.
Methods: We showed that a novel topical DNA vaccine
(DermaVirtm) could transduce epidermal Langerhans cells,
prompt them to migrate to the lymph node, mature to SIV/HIV
antigen-expressing dendritic cells and elicit potent HIV-specific
T cell immunity. To study the effect of DermaVir therapy we
conducted two separate studies on 26 chronically SIV251 -infected rhesus macaques and an additional lo macaques
already showing signs of AIDS. Monkeys were randomized to
receive HAART, STI (3 weeks on HAART & 3 weeks off),
STI+DermaVir and DermaVir alone.
Results: Unlike 7 chronically infected animals receiving STI alone,
the 7 randomized to receive STI+DermaVir progressively
controlled viral rebound during treatment interruptions from a
median 33,860 copies/mi to <200 copies/mi. Six macaques
treated with DermaVir alone experienced no increase in viral load
and survived longer than the untreated controls. The macaques
with AIDS started the STI+DermaVir treatment with a significantly
higher viral load and suppressed viral rebound from a median
4,292,260 to <200 copies/mL. Control of viral load in the absence
of therapy was associated with augmented SIV-specific CD8 and
CD4 T cells as measured by IFN-gamma intracellular cytokine
assay. DermaVir therapy did not show signs of toxic side effects.
Conclusion: These primate trials constitute the first evidence
of the antiviral efficacy of a therapeutic vaccine measured by
viral load suppression during treatment interruption and
delayed disease progression. The simplicity of the DNA
formulation and topical application, as well as the antiviral
potency and safety of DermaVir, make it a very attractive
vaccine for the treatment of HIV/AIDS.
Corresponding author: Lisziewicz, Julianna, Research Institute
for Genetic and Human Therapy, 2233 Wisconsin Ave, NW,
Suite 503, Washington, DC 20007, United States,
Tel: [phone], Fax: [phone],
Email: [email protected]

LBOR121
Strong CD4+ T cell responses to HIV antigens in treated
patients is not predictive of restriction of viral replication
Tilton, John, lyasere, Christiana, Migueles, Stephen, Laborico,
Alisha, Connors, Mark (United States)
Background: Proliferative responses to H IV antigens are
absent in most untreated patients despite persistence of
significant frequencies of HIV-specific CD4+ T cells. Strong HIVspecific CD4+ T cell responses to viral antigens are thought to
contribute to restriction of virus replication. The HIV-specific
CD4+ T cell responses and ability to restrict virus replication
was studied in a cohort of patients with strong HIV-specific
CD4+ T cell responses during serial interruptions of therapy.
Methods: Thirteen patients with progressive disease with
proliferative responses while on therapy (cpm 1671-19674)
were recruited. Patients were leukopheresed prior to, during
and after therapy interruption. T cell frequencies and
proliferation to gag, pol and nef peptide pools, p24, CMV and
tetanus antigens were determined.
Results: Although proliferative responses to HIV antigens
before therapy interruption were equivalent to those of
nonprogressors, responses were rapidly and completely
abrogated during viremia following interruption. Proliferation
returned with viral suppression upon therapy resumption. High
frequencies of total HIV-specific CD4+ T cells were present in
all subjects (mean 0.59%; range 0.17-1.52%). These
frequencies persisted during viremia for all antigens (p>o.o5);
gag (mean 0.29% on therapy vs 0.43% off therapy), pol (.09 vs.09) and nef (.11 vs.09). The frequency of IL-2 producing HIVgag or CMV-specific cells was not significantly diminished
(p>o.5). Proliferation to HIV antigens prior to treatment
interruption was not predictive of viral restriction off therapy
(1-5 interruptions; viral loads: mean 31,651; 74-113,269).
Conclusions: Proliferative responses to H IV antigens were not
predictive of control of viremia. During viremia, proliferation of
HIV-specific CD4+ T cells was rapidly and completely
abrogated. These data strongly suggest that HIV-specific CD4+
proliferation appears to be a result, rather than a cause, of
effective viral restriction.
Corresponding author: Tilton, John, National Institutes of
Health, io Center Drive, Room 11Bo5, Bethesda, MD 20892,
United States, Tel: +i 3014960311, Fax: +i 3014020070,
Email: [email protected]
LBOR13I
Preliminary analysis of a randomised controlled study to
assess the role of post-exposure prophylaxis in reducing
mother to child transmission of HIV-1
Gray, Glenda, Urban, Mike, Violari, Avye, Chersich,
Matthew, van Niekerk, Ronelle, McIntyre, James (South Africa)
Background: To date, Nevirapine prophylaxis to mother and
infant provides the most feasible option for the prevention of
Mother to child transmission (MTCT) of HIV-1 in developing
countries. What is not known is the value of post-exposure
prophylactic (PEP) antiretroviral therapy in reducing MTCT
where women did not access therapy during pregnancy or
labour. We are investigating the role of PEP in reducing the risk
of MTCT comparing two drug regimens given to the HIV
exposed infant in three hospitals in South Africa.
Methods: Randomised open label trial of the use of single dose
Nevirapine(NVP) vs. 6 weeks of Zidovudine(ZDV) administered
post-natally to infants born to HIV infected women who have had

XIV International AIDS Conference BARCELONA - JULY 7-12

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