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

782 Abstracts 41199-41204

12th World AIDS Conference

identified several amino acid substitutions in the V3 and V4 region, and in close
proximity to the disulfide bridges of the V3 and V4 loops. Unexpectedly, however,
none of them were at the same position in three resistant strains.
Conclusions: It required relatively long-term passages to develop
mCDS71-resistant HIV-1 in vitro. The conformational change of the V3 and
V4 loops led by the accumulated amino acid substitutions is likely to contribute to
the development of the mCDS71-resistance.
41199 Solidarity network of people with HIV/AIDS
Rodolfo Solano. PO. Box 5427-1000 San Jose 100 meters North Centro
Comercial Guadalupe, Costa Rica
Issue: The Costa Rica HIV/AIDS population has increased dramatically and
requires urgently further information on how to give emotional, social, and economical support which could improve the quality of life of all of us whom have
HIV/AIDS.
Proyect: Because of the conditions of those like us who live with HIV/AIDS, we
are trying to establish a proyect called "Solidarity Network". This proyect includes
various items such as: Preparing the people with HIV/AIDS and their families,
through chosen agents who will receive the necessary preperation in the Hospital
San Juan de Dios. This will go through a process of empowerment of people with
HIV/AIDS, making them assume their own responsabilities. Another item would
be creating a market of jobs for those affected with HIV/AIDS and permit them to
have an income to maintain their necesities.
Results: The first asociation has already been formed in Costa Rica by
HIV/AIDS patients coming from the Hospital San Juan de Dios, although there is
a larger group of people with HIV/AIDS that is being attended in the country.
Lessons Learned: A fight for the antiretrovirals to be able to live in public like
normal human beings, even though we have HIV/AIDS, and to be capable to be
part of the society and therefore, to be part of the Costa Rican community.
41200 Synthesis, chiral separation and anti-HIV activity of
enantiomeric oxaselenolane nucleosides
David C.K. Chu1, R.F. Schinazi2, L. Ma2, J. Du1, S. Wirtz2, J. Shi2, C. Pierra1.
1374 PBS, R.C. Wilson Pharmacy, Univ of GA; 2Emory University, VA. Medical
Center, Decatur, GA, USA
3'-Heteroatom substituted nucleosides, such as 3TC, FTC and DAPD have generated great interest to the scientific and medical community as anti-HIV and
anti-HBV agents because of their potent in vitro and in vivo antiviral activities,
unique resistance patterns, as well as favorable toxicity profiles. In view of these
interesting and promising aspects of 3'-heteroatom substituted nucleosides, we
have recently synthesized racemic oxaselenolane nucleosides. We have now
successfully resolved the /-enantiomers of the 5-fluorocytosine oxaselenolane
derivatives by chiral HPLC. Studies in HIV-1 infected primary human lymphocytes
indicated that the (-)-f-enantiomer (mean EC50 = 0.21 p/M) was 200-fold more
potent than the (+)-/-counterpart. Biological activity (e.g., anti-HIV and toxicity)
and physical characteristics of this new series of selenium containing enantiomers, including the cytosine analogs compared to the corresponding, dideoxy-,
dioxolane-, and oxathiolane-nucleosides were compared.
Results indicate that modifications at the 3'-position from CH2, to O, S, or Se
can have a major impact on the potency, toxicity, and cross-resistance profile of
these enantiomeric 3'-heteroatom substituted nucleosides.
Supported by NIH grant Al-32351, AI-41980, and the VA.)
41201 Two- and three-protease inhibitor combinations against
zidovudine-sensitive and zidovudine-resistant HIV-1
isolates in vitro
Cecile Tremblay12, D.P. Merrill2, T.C. Chou2, M.S. Hirsch1. 1MGH, Infectious
Disease Unit, Gray 5 Fruit St. Boston, MA, 2Memorial Sloan-Kettering Cancer
Center, New York, NY, USA
Background: Protease inhibitors used in combinations with reverse transcriptase
inhibitors have demonstrated very potent antiretroviral activity in vitro as well as
in vivo.
Project: We evaluated the interactions of four protease inhibitors: indinavir
(IDV), ritonavir (RTV), saquinavir (SQV) and amprenavir (APV), when used together in 2- and 3-drug combinations in vitro.
Results: Against a zidovudine-sensitive isolate, the 2-drug combinations: SQV
+ APV, SQV + RTV, RTV + APV, IDV + RTV and the 3-drug combination: APV
+ SQV + RTV showed synergistic effects. The 3-drug combination APV + SQV
+ IDV showed additive effect. SQV + IDV + RTV showed additive to synergistic effect. Against a zidovudine-resistant isolate, SQV + APV and SQV + RTV
showed synergy. However, the 2-drug combination APV + RTV as well as the
3-drug combination SQV + RTV + APV showed additive to antagonistic effect.
Similar patterns were observed against a multi-nucleoside resistant isolate with
synergy observed with SQV + APV and SQV + RTV combinations and antago
nism observed with APV + RTV. Against this multi-nucleoside resistant isolate,
the 3-drug combination SQV + RTV + APV showed additive effect.
Conclusions: In conclusion, combinations of protease inhibitors in vitro may
give synergistic, additive or anti-HIV effects, depending on the agents employed
and the viral isolates studied.

41202 Methadone and protease inhibitors in HIV-infected drug
abusers
Gianpiero D'Offizi1, G. Campitelli1, R. Urso1, C. Carvelli1, G. Cerasari1,
M. Zaccarelli2, P. Narciso1. 1L. Spallanzani Hosp. I.R.C.C.S. IV Div, Via
Portuense 292 00149 Rome; 2L. Spallanzani Hosp. I.R.C.C.S. I/I Div Rome, Italy
Objectives: To assess the influence of methadone maintenance on highly active
antiretroviral therapy (HAART) in HIV positive intravenous drug users (IDUs). We
evaluated the safety, the tolerability of protease inhibitors (PIs), the compliance
and the efficacy of HAART in a cohort of patients followed at L. Spallanzani
Hospital in Rome.
Design: Follow-up study.
Methods: We retrospectively recorded the adverse events (AE), compliance,
the change of HIV-RNA copies and CD4 cell count in all of the IDUs receiving a
standard therapy with two nucleosides analogues and a PI. The mean dosage of
methadone was 0.5 ml/kg/daily. The control group consisted of 21 HIV infected
patients treated with HAART.
Results: We enrolled 55 IDUs (25.4% naive) receiving indinavir (IDV 32),
ritonavir (RIT 7), saquinavir (SQV 16) over a 6 month period. 13 controls received
IDV, 3 RIT and 6 SQV. HCV antibodies were present in 41/55 (74.5%) and in
12/21 (57%) controls. After a follow-up of 6 months IPs regimen, in methadone
group, was stopped for 11 patients (20%): 4 (7.2%) gastrointestinal intolerance,
2 (3.6%) renal colic, 2 ALT elevation, 1 anemia and 2 cases of neuropathy. In
controls was stopped for 8 patients (38%): 2 (9.5%) gastrointestinal intolerance,
2 renal colic, 3 (14.2%) anemia, 1 ALT elevation. 2 IDUs and 1 control voluntarily
stopped HAART and 90% of patients were compliant with antiretroviral therapy.
After 6 months the mean increase in absolute CD4 T cells was 75 in methadone
group and 123 in controls. In all patients tested for viremia, a mean drop of 1.74
log was observed, without significant differences between the two groups.
Conclusion: In our study methadone maintenance coadministered with PIs
does not seem influence in terms of antiviral potency, immunological restitution
and frequency of AE. PIs were safe, effective and well tolerated in the IDUs
with methadone maintenance which were compliant with their therapy. Adverse
events like renal colic and gastrointestinal intolerance were not more frequent
in these patients. Others pharmacokinetic studies are needed to provide further
informations concerning methadone coadministrated with PI.
41203 Anti-human immunodeficiency virus type 1 activities of
proteins from 17 species of plants
Kun Long Ben, Y.T. Zheng. Kunming Institute of Zoology, Chinese Academy of
Sciences, Kunming, Yunnah 560223, PR. China
Objectives: To find new anti- HIV-1 ribosome-inactivating proteins (RIPs)
Methods: The anti-HIV-1 activities of 57 RIPs and crude proteins from 17
species of plants were examined by the following measurement: 1) the inhibition
of syncytia formation; 2) the protection of HIV-1 infected cell; 3) inhibition of
HIV-1 infected cell fusion in coculture; 4) reduction of p24 antigen expression and
numbers of HIV antigen positive cells in acutely and chronically infected culture.
Results: Among 57 proteins, trichosanthin (TCS) (SI = 193.3), trichobitacin
(SI is between 300-900) from Trichosanthes kirilowii, a-momorcharin (u-MMC)
from Momordica charantia (SI = 332), Protein fractions V (SI = 243) and VI
(SI > 1200) from Trichosanthes damiaoshanesis were found to obviously inhibit
syncytia formation induced by HIV-1. Crotin I from Croton tiglium, luffin from Luffa
cylinarica, RIPs from Hodgsonia macrocarpa and Entada phaseoloides showed
slight inhibition of the syncytia formation (SI < 50). Crude protein extracts from
Trichosanthes ovigera, Momordica macrophylla and an unnamed plant growing in
Xishuangbanna district, Yunnan province, obviously inhibited syncytia formation,
but proteins purified from them lost their activities. All RIPs were unable to block
HIV infected cell fusion in coculture, and did not protect HIV-1 infected MT-4 or
C8166 cells from dying. TCS, a-MMC and trichobitacin markedly reduced both
expression of p24 core protein and the numbers of HIV antigen positive cells in
acutely but not chronically HIV-1 infected culture.
Conclusion: In addition of TCS and the other known RIPs, trichobitacin is
a novel anti-HIV ribosome-inactivating protein. ac-MMC is a main component of
momorcharin with anti-HIV activity.
41204J HIV infection inhibitors: Carbohydrate-containing
biopolymers (CCBs) of bacterial and lymphoid cells
Svitlana L. Rybalko1, W. Anatoly Shapiro1, T. Dyadun Svitlana1, Grytsak Tanja1,
V. Nesterova Nadya2, S. Dyachenko Nata2, Varbanets Ljuda2, N. Zherentsova
Ella3, Ivanskaja Naiija3, M. Shcherbinskaja Alia1. 1 Institute of Epidemiology and
Infective Diseases, Kruglouniversitetskaja Str. 14, F. 19, 252024 Kiev; 2lInstitute
of Microbiology and Virology of Academy of Sciences, Kiev; 3lInstitute of Molec.
Biol. of Academy of Science, Kiev, Ukraine
Objectives: To study some patterns of anti-HIV effect shown for some CCBs
from culture fluids of bacterial and lymphoid cells growing in suspension.
Design: Research of antiviral (anti-HIV) substances.

Methods: Cultivation of bacterial and lymphoid cells. An ethanol fractionation
method followed by gel filtration (Sepharose 4B) is proposed for the CCB isolation.
The amino acid, carbohydrate, and fatty acid contents of the CCB were studied
as well as the CCB effect on different HIV functions (DNA-polymerase, thymidinekinase, and reverse transcriptase activity) and antigenic relations between viral
and bacterial peptides.