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

12th World AIDS Conference

Abstracts 22423-22427 349

224231 A single center, phase 2 study evaluating the effects of
WF10
James O. Kahn1, Michael S. Mc Grath1, OM. Ah Ching2, FW. Kuhne2. 1995
Potrero Ave. Bldg 80 Ward 84 USA;2UCS AIDS Program, San Francisco CA,
USA
Background: Anti-retroviral therapy may be optimized by concurrent use of a
therapeutic modality which reduces the occurrence of opportunistic infections.
We investigated WF10, which is a novel compound formulated from the unique
chlorite-oxygen reaction product, tetrachlorodecaoxygen anion complex. WF10's
activity stems from its ability to directly and/or indirectly activate macrophages by
binding to membrane-bound heme complexes. Macrophage activation is central
to wide variety of immune responses.
Method: We performed a Phase 2 study with 18 subjects who had >50 CD4
cells and viral load of <20,000 copies/ml. Subjects were administered WF10 at a
dose of 0.5 ml/kg given as an intravenous (IV) infusion for 5 consecutive days.
After a 16-day rest period this treatment was repeated. Immunologic parameters,
T-cell phenotype and viral RNA were assessed. Phagocytic index was also used
to measure macrophage activation.
Results: 16 subjects completed the study. All subjects received combination
anti-HIV treatment. Baseline mean plasma HIV RNA was 3084 copies/ml and
baseline mean CD4 count 327 cells. WF10 was well-tolerated without any significant clinical or laboratory toxicities. There were no apparent changes in viral
RNA during the study. A significant increase was seen in lymphocytes with a phenotype of: CD3+/CD8+/CD28-, and significant decreases were observed in cells
with the following phenotypes: D14+/TNF+, CD14+/DR+, CD3+/CD4+/CD38+,
CD3+/CD8+/CD28+, CD20+/DR+, and CD14+. Persons with a low phagocyte index increased their index score. These patients also had lower CD4+ cell counts
at the initiation of the study. Persons with a high phagocytic index demonstrated
a reduction in their index score.
Conclusions: WF10 administration is safe for IV administrations in an outpatient setting. The increase in CD8+ cell number with concomitant decreases in
markers of immunologic activation (CD38+, DR) was coupled with an increase
in macrophage activation, without an increase in viral load. These observations
suggest that WF10 might be useful for functional augmentation of macrophages,
which constitute the last cellular immune component present in patients with
advanced HIV disease.
22424 Inhibition of HIV-1 replication in reservoir cells by the
safe immunomodulator murabutide
Georges Bahr, E. Darcissac, O. Grau, M.J. Truong, J. Dewulf, C. Debard,
A. Capron. Institut Pasteur de Lille, INSERM U167, 1 Rue du Professeur
Calmette 59019 Lille, France
Objectives: To assess the efficacy of the clinically-acceptable immunomodulator
Murabutide, a butyl ester derivative of MDP, on the inhibition of HIV replication in
monocyte-derived macrophages (MDM) and dendritic cells (MDDC).
Methods: Acutely infected MDMs and MDDCs with M-tropic HIV-1 isolates,
were maintained in the absence or presence of Murabutide. Reverse transcriptase (RT) or P24 levels in culture supernatants were evaluated 7-21 days
post-infection. Proviral DNA and viral mRNA were quantified in infected cells
using polymerase chain reaction (PCR) and RT-PCR respectively. The levels of
secreted cytokines were also tested by specific ELISA kits.
Results: Addition of Murabutide to infected MDMs and DCs resutled in
60-100% inhibition of viral replication in cultures from 10 different donors. This
effect was found to be mediated, in part, by the induction of high levels of HIVsuppressing beta chemokines, MIP-la, MIP-1/l and RANTES. In addition, cells
stimulated with Murabutide immediately after infection presented highly reduced
levels of proviral DNA at the 24 hour period. Analysis of the levels of unspliced
and singly-spliced viral mRNA in 8-12 days infected cells showed over 90%
inhibition of viral transcripts in Murabutide-treated cultures. This inhibitory effect
of Murabutide was also evident in reservoir cells acutely infected with primary
HIV-1 isolates.
The safe synthetic immunomodulator Murabutide exerts potent HIV-suppressing activity in reservoir cells and is currently being evaluated as an adjunct to
antiretroviral therapy.
22425 Title not indicated
Dennis Leon, M.A. Rodriguez, V.M. Rodriguez, C.A. Soto, M. Calderon. Facultad
de Microbiologia U.C.R., University of Costa Rica, San Jose, Costa Rica, Costa
Rica
Objectives: To develop an alternative therapy for HIV+ patients that is less costly
for developing countries and improving life expectancy and quality of life.
Design: Phase II prospective study.
Methods: Adult male patients with CD4+ counts ranging from 600-9 were included. Evaluation of levamisole treatment was based in CD4+ and CD8+ counts
and by clinical improvement of the patients. Renal and hepatic function tests were

conducted to determine toxicity.
Results: Administration of a combination of levamisole and an antiretroviral
drug as AZT and/or 3TC could act at three levels: a. inhibition of the viral replication
by the antiretroviral therapy. b. inhibition of viral replication by the restored immune
system due to the immunostimulatory therapy. c. Less secondary infections due
to a more effective immune system and therefore a slower or non-existent progression to AIDS. Increases were observed in one patient receiving levamisole,

AZT and 3TC from 9 to 429 CD4+ lymphocytes after 5 months of treatment and
another one receiving levamisole and AZT from 270 to 415 CD4+ after 8 months
of treatment. Additionally an experiment was conducted in 10 patients receiving
only levamisole and the observed mean increase was from 551 to 722 CD4+
though further increases were not observed on the follow up.
Conclusion: Levamisole is an excellent alternative treatment for HIV infected
patients, increase in CD4+ lymphocytes is very significant and the cost of the
treatment compared with available therapies is roughly a third.
46*/22426 Euthanasia: The opinion of Europeans with HIV
infection
Yon Fleerackers1, R. Andraghetti2, J.C.C. Borleffs3, N. Ferro4, P. Sas5,
R. Colebunders1. 1Eurosupport Group, Institute of Tropical Medicine Nationale
Straat 155, B - 2000 Antwerpen, Belgium; 2Universita "Tor Vergata", Rome, Italy:
3University Hospital Utr echt, Utrecht, The Netherlands; 4Liga Portugeusa
Contra A Sida, Lisbon, Portugal; 5Comita de Lucha Contra El Sida, Barcelone,
Spain
Objective: To evaluate the opinion on euthanasia of persons with HIV infection
living in the European Union (EU).
Methods: End 1996 - mid 1997 an anonymous questionnaire survey was organised among person with HIV infection, known to be HIV seropositive since at
least 1 year. Questionnaires were distributed in 11 European countries by 15 HIV
treatment centres and 9 support organisations. In the 22 page questionnaire the
patient's perception on a wide range of support/care issues, including euthanasia,
was evaluated.
Results: Of the 1299 respondents 43% considered themselves to be asymptomatic, 33% symptomatic but not having AIDS, 19% to have AIDS; 7% did not
mention their stage of disease. Seventy three percent (range: 65% in Greece -
92% in Belgium) felt that physicians should have the legal right to help terminate
the life of an HIV-infected person at his/her clear request in case of severe
physical suffering; 52% (range: 19% in Greece -81% in Spain) in case of severe
psychological suffering; and 27% (range: 16% in Luxembourg - 41% in Spain)
simply on demand. Fifty six percent (range: 38% in Spain - 73% in Portugal)
mentioned that if euthanasia in case of severy physical suffering became possible
in their country, this would take away some of their anxiety about the future.
Fifty four percent (range: 40% in Greece - 71% in United Kingdom) mentioned
they would ever consider asking for euthanasia when they would have no more
treatment options left. Sixteen percent (range: 7% in Italy - 35% in Portugal) had
already discussed the possibility of euthanasia with a physician.
Conclusions: A majority of persons with HIV infection in Europe are in favor of
allowing euthanasia by law under certain conditions. This is in contrast with the
fact that for the moment this is only possible in the Netherlands.
505*/22427 Palliative care for HIV infection in a skilled nursing
facility
Peter A. Selwyn1, K.P. Fennie1, S. Molde2, J. Constantino, Sr.2, P. Wetherill2,
L. Goldman1, C. Kennedy2. 1 Yale AIDS Program 135 College St. New Haven,
CT; 2Leeway, Inc., USA
Background: Advances in HIV therapy have resulted in reduced mortality, but
have also led to prolonged survival among late-stage, debilitated patients. In response to the resultant need for long-term, palliative care, skilled nursing facilities
for people with AIDS have been established as a new model of care delivery. We
describe the characteristics and outcomes of consecutive admissions to Leeway,
a 30 bed, free-standing, skilled nursing facility for people with AIDS, in New
Haven, CT, established 1/10/95.
Methods: Systematic record review of all admissions to the facility from
1/10/95-3/7/97 (22 months).
Results: The facility has remained filled to >80% capacity since opening. Of
134 admissions (112 individuals), 67% have been referred from local hospitals,
33% from other institutions/outpatient sites. Reasons for admission were: need
for 24-hour nursing care (60%), completion of acute medical treatment (16%),
terminal care (15%), pain management (5%), and respite care (4%); 70% of
patients were male, 30% female; mean age 40 yrs.; 63% had a history of injection
drug use. Median Karnofsky score was 40, median mini-mental status exam
(MMSE) score 24/30; 89% were CDC stage C3 (median no. prior AIDS-indicator
illnesses, 3.5), baseline CD4+ count 15 cells/mm3, viral load 77,500 copies/ml.;
66% had neurologic disease, including HIV dementia, myelopathy, neuropathy,
PML, or stroke. 39% patients were discharged home, 35% died, and 26% have
become long-term residents of the facility (median length of stay for the latter: 268
days). Overall median length of stay was 59 days (range 1 to 399). Significant
predictors of mortality included: baseline Karnofsky score (p < 0.01) and MMSE
score (p < 0.01).
Conclusion: A dedicated skilled nursing facility can meet important care needs
for late-stage patients with AIDS. Clinical services in such settings must address
the high prevalence of neurologic disease, functional impairment, substance
abuse disorders, and the need for bereavement counseling for patients, families

and staff.