Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

790 Abstracts 41237-41242

12th World AIDS Conference

41237 TNF-a and HIV-specific functional immune responses
after treatment with a gp 120-depleted, inactivated HIV-1
in incomplete freund's adjuvant (RemuneT) in HIV-1
seropositive subjects
Ronald Moss1, L. Li1, W.K. Giermakowska1, P. Lanza, J.L. Turner2,
M.R. Wallace3, F.C. Jensen1, S.P. Richieri1, A.E. Daigle1, G. Theofan1,
D.J. Carlo1. 1The Immune Response Corporation 5935 Darwin Court Carlsbad
CA 92008; 2Graduate Hospital University, Philadelphia, PA; 3US Naval Medical
Center, San Diego, CA, USA
Background: Proinflammatory cytokines such as TNF-a have been associated
with viral replication and disease progression in HIV-1 infection. We examined
the relationship between TNF-a levels and HIV-1-specific functional immune responses, as measured by HIV-1 antigen stimulated lymphocyte proliferation and
t chemokine production after treatment with a gp 120 depleted inactivated HIV-1
in Incomplete Freund's adjuvant (HIV-1 Immunogen, REMUNE'.
Methods: Eleven HIV-1 seropositive subjects enrolled in an open label study
were treated with REMUNET' every 12 weeks and followed for 60 weeks. HIV-1
antigen stimulated lymphocyte proliferation and RANTES production were measured in PBMCs. TNF-a levels were measured in serum.
Results: TNF-a, (p = 0.0003) significantly decreased, while HIV-1 antigen stimulated RANTES production (p = 0.002) and lymphocyte proliferation (p = 0.07)
increased after treatment with REMUNE'T. Furthermore, TNF-0a levels negatively
correlated with HIV-1 antigen stimulated RANTES production (r = -0.71, p =
0.0002) and lymphocyte proliferation (r = -0.37, p = 0.09).
Conclusions: This study has demonstrated a decrease of TNF-a levels with a
concomitant augmentation of HIV-specific functional immunity in subjects treated
with REMUNE0". As TNF-a has been implicated in the induction of anergy in HIV-1
infection, the ability to decrease it may allow the immune system to respond to
HIV and non-HIV antigens. Larger studies are ongoing to confirm the clinical utility
of REMUNETM in combination with potent antiviral drugs.
41238 Treat AIDS and ARC with Chinese traditional medicine
"extract spring of life" (ESOL) - A report of 65 cases
Yong-Kong Li1, Ming Li2, Wang Kun3, Wu Lu-ming3. 1 Yong Kang Chinese
Traditional Medical Hospital, No. 1 of Mu Fan Road, 430016, Wuhan, Hubei
Province; 2Kunming; 3Lu-xi, PR. China
Objectives: To sift the Chinese traditional medicine-ESOL for treating AIDS and
ARC.
Design: Controlled study.
Methods: The essential research included inhibiting test for HIV and P24Ag,
cellular and humoral immune functions for mice and MIC for multiple bacteria etc;
in clinical studies, selected patients of AIDS and ARC according to the diagnostic
criteria of CDC 1987 and WHO 1990; the cases of therapeutic group took ESOL
15 g Bid for 3 months each course and one cases of control group Look placebo
with symptomatic treatment. According to symptoms, signs, bodyweight, X-ray
of chest, ECG, HIV-Ab, HIV-P24g, total lymphocytes, CD4 CD8 lymphocytes,
complement C3 and IgG, the liver function, renal function, effective rate and
survival time to compare the results.
Results: The essential studies snowed that Esol could inhibit the HIV-1 and
HIV-2, the P24Ag became negative;the MIC studies suggested that ESOL could
inhibit the generation for some bacteria; Among of 65 cases, 35 cases (53.8%)
have a significant effect, 20 cases (30.8%) have a mediate), 2 cases (3.1%) have
no effect and 8 cases (12.3%) died. Among the 25 cases, of AIDS, the survival
time of 15 cases was over 4 years.
Conclusion: This paper and MEDLARS showed that ESOL not only increased
the immune functions but it has got a stronger inhibiting effect for HIV, and the effective rate was higher than other prescriptions of Chinese traditional medicine in
1985-1997. Compared with control group, the results have a statistical significant
difference (P 0.001).
41239 Induction of specific anti-HIV-1 IgY produced in species
pathogen free chickens
Carmen Soler Claudin1, Amalia Barquet Fuentes1, E. Lucio Decanini2,
A. Romero2, A. Morales Garzon2, M.E. Gonzales Castaheda2. 1 Unidad de
Investigacion En Retrovirus Humanos Facultad de Quimica Unam/lndre SSA,
Carpio #470 Col. Sto. Tomas 11340 Mexico; 2lnvestigacion Aplicada Sa de Cu,
Tehuacan Puebla, Mexico
Background: Different studies have demonstrated the usefulness of IgY as a
means for passive immune therapy. The IgY are transported from the chicken
to the egg by a process similar to transplacental transfer in mammals; therefore
they can be obtained from yolks in high concentrations (9 to 25 mg/ml). The
presence of enhancer antibodies in some viral infections has been demonstrated
to be mediated by complement or Fc receptors for IgG. On the other hand, IgY
produced in eggs do not bind to either mammalian Fc receptors or complement,
so that IgY cannot be enhancing antibodies.

Objectives: To induce specific anti-HIV-1 IgY antibodies in chicken species
pathogen free (SPF) and to determine if they have neutralising capacity for HIV-1.
Methods: IIb/LAV prototype virus was obtained from supernatant of Molt cells
and purified with a fast flow Sepharose 4B column and gp 160 recombinant
protein from Advanced Biotecnologies Incorporated. Five SPF chickens (ALPES,
Tehuacan Puebla) were immunized four times; the first three immunizations consisted of an emulsified mixture of purified virus at a concentration of 8 t/g per

chicken, the fourth immunization was with recombinant gp 160 at a concentration
of 3.74 t/g per chicken. Preimmune sera and eggs were obtained before the first
immunization and immune sera and eggs every week thereafter.
Results: IIIb/LAV ELISA showed the presence of high titer HIV-specific IgY
antibodies in sera and in the purified IgY yolk fractions of the 5 immunized chickens. Western Blot assays with the same antigen demonstrated the presence of
specific anti-HIV-1 antibodies against p17, p24, p31, (weak) p41, p51, p55 and
p66. No clear response to gp120 was observed.
Conclusions: To our knowledge this is the first report of HIV-1 specific IgY
antibodies reproducibly induced in SPF chickens. This technique will be usefull
in testing the neutralising capacity of these antibodies as a preliminary step for a
passive immune therapy alternative.
41240 The use subcutaneous recombinant interleukin-2 with
antiretroviral therapy in HIV infection
Jorge Eurico Ribeiro12, L.B. Castro3, M.A. Silva3, M.B.C. Lima3. 1Rua Campos
Salles 37/102-a Tijuca, Rio de Janeiro, RJ; 2University of Rio de Janeiro,
Uni-Rio, Rio de Janeiro, RJ; 3Uni-Rio Clinica Medica A, Rio de Janeiro, RJ, Brasil
Objectives: Compare the results obtaind on the treatment of HIV patients (PT)
using antiretroviral combined therapy (ACT) only with the results of other PT
using subcutaneous recombinant Interleukin-2 (rlL-2) associated with ACT.The
influence of rlL-2 over the CD4 cells and collateral effects, toxity levels and
therapy efficiency.
Design: Prospective, controlled study.
Methods: A total of 36 PT infected by HIV, under ambulatorial care, ages
from 20 to 55 years, both male and female, with a number of at least 200 CD4
cells/mm3, using ACT for more than 6 months and with a viral load under 1000
conts of RNA of HIV (PCR method),were observed. No acute infections were
observed at that moment. Those PT were separeted in 2 groups: Group 1 - PT
using only ACT (control group) and Group 2 - PT using ACT that hav also received
rlL-2 (PROLEUKIN), subcutaneously, in doses of 18 MIU/day on a 5-day cycle,
every 8 weeks in 3 cycles. Every PT was checked,before and after each cycle,
on immunologic, virologic an bioquimical basis.
Results: Group 1 presented a mean of 378 CD4 cells/mm3 on the beginning
of the study, and 399 in the end. In group 2, a initial mean of 349 and 686 CD4
cell/mm3 in the and, without toxity levels.
Conclusion: This study shows that the use of rlL-2 associated with ACT proportionates a significant increase of the number of CD4 cells/mm3 (a mean of
98.3%), reinstating, therefore, the immunologic system,keeping the viral load low.
141241 Clinical trials of stem cell gene therapy for HIV-1
Gerhard Bauer1, J.A. Zaia2, J. Ito2, P. Valdez1, J.C. Rothschild1, S. Li2,
D. Castanotto2, H. Li2, P. Yam2, J. Rossi2, S.J. Forman2, D.B. Kohn1. 1Childrens
Hospital Los Angeles CA 4650 Sunset Blvd #62 Los Angeles CA 90027; 2City of
Hope National Medical Center Duarte CA, USA
Background: Hematopoietic stem cells may be a useful target for the introduction
of genes which inhibit HIV-1 replication since they produce essentially all the cells
involved in HIV-1 infection and pathogenesis. A number of genes designed to
inhibit HIV-1 replication were evaluated in different retroviral vector configurations,
which led to the identification of several vector constructs as being strongly and
consistently inhibitory to HIV-1 replication in in vitro assays using transduced
human CD34+ hematopoietic progenitor cells. Two anti HIV-vector constructs, a
double hammerhead ribozyme and an RRE- decoy have now been evaluated in
phase-1 clinical trials to determine 1) the safety and feasibility of isolating and
transducing stem cells from HIV-1 (+) donors, 2) the ability of the transduced
cells to engraft and produce gene containing mature hematopoietic and lymphoid
cells, and 3) whether expression of a gene which inhibits HIV-1 replication can
confer a selective survival advantage to HIV-1 target cells in vivo.
Methods: In separate clinical trials, CD34+ cells were obtained from G-CSF
mobilized peripheral blood of HIV-1 infected adults, and from bone marrow of
HIV-1 infected children. In the adult study, CD34+ cells were transduced with a
vector containing the double hammerhead ribozyme, CD34+ cells from children
were transduced with the RRE decoy vector.
Results: Preliminary results show high transduction frequency into CD34+
cells (approx. 40 to 80% measured by G418 resistance and neo-DNA PCR), and
safety of the procedure with no adverse events seen in patients after reinfusion of
autologous stem cells. In two out of three patients having reached the six month
time point after infusion, gene containing cells can be detected in bone marrow
or peripheral blood. Long term studies to evaluate the production and selective
survival of anti HIV-gene containing lymphoid cells are currently being conducted.
Conclusions: High transduction efficiencies into CD34+ cells obtained from
HIV-1 infected individuals in a clinical setting can be achieved routinely, and it is
feasible and safe to proceed to phase-2 clinical trials of stem cell gene therapy
for AIDS.

141242 Inactivation of HIV-1 coreceptors by intrakine
Si.-Yi Chen. Dept. Cancer Biology, Hanes Bldg. 4019, Wake Forest University,
School of Medicine Winston-Salem, NC, USA
Genetic defect in a CC-chemokine receptor (CCR)-5, the principal co-receptor for
the macrophage (M)-tropic human immunodeficiency virus (HIV)-1, was recently
found to naturally protect these genetic defect, but healthy individuals from HIV-1