[Final Program, International Conference on AIDS (4th: 1988: Stockholm, Sweden), Book 2]

3513 INACTIVATION OF HIV DURING MANUFACTURING
PROCEDURES OF HUMAN LEUKOCYTE INTERFERON
Karoly Nagy, F.Peterfy, E.Drexler, K.Onody*
Institute of Isotopes, Hungarian Academy of Sciences and
EGIS Blood Product Laboratory, Budapest, Hungary
Objective. Manufacturing procedures of human leukocyte
interferons (huo-IFN) had been studied for the ability
of effective inactivation and/or elimination of HIV.
Methods Crude interferon preparations were spiked with
HIV (I0ID5nml ), and than subjected to i., pH=2 treatment, ii., ethanol precipitation, iii., controlled-pore
glass (CPG) microbead separation. HIV titers of HIV/IFN
mixtures as well as purified IFN preparation were determined by H9 infectivity assay, fixed cell immunefluorescence, reverse transcriptase assay and Abbot Envacore EIA
for p24 and gp41.
Results. HIV was e fectively inactived by pH=2 treatment
within 30 min at +4 C, and viral antigens had been decreased by> 99%. Minimal antigen titre could be detected after
16 h treatment. 60% ethanol precipitation was also effective, because HIV had been inactivated completely after
10 min at -200C. This treatment decreased antigen-titer
by only 50%. CPG microbead column was suitable for separation of IFN from HIV. In the eluent containing IFN biologically active HIV could not be detected. This procedure
reduced HIV antigens by 2.5 log. In final preparations of
purified huoc-IFN neither infectious HIV nor HIV specific
antigens have been found.
Conclusion. Procedures studied inactivated HIV by more
than four orders of magnitude. The final products do not
contain any infectious HIV, which are thus safe, and they
cannot be vehicles for the transmission of AIDS.

3514 LENGTH OF SURVIVAL OF 100 PATIENTS WITH
AIDS-RELATED KAPOSI'S SARCOMA (KS) TREATED
WITH RECOMBINANT 0(2 INTERFERON. S.Gharakhanian, B.Cardon
M.S Navarette,W.Rozenbaum, Hopital Claude Bernard, Paris
OBJECTIVE: To establish lenght of survival for a group
of patients with Kaposi's Sarcoma treated by recombinant
Alpha-2 Interferon (INF).
METHODS: Between March 83 and Dec 87, we treated 100
male KS by INF (18 million u/day; mean duration 168+77
days). Mean duration between diagnosis and treatment
was 60+98 days. Patients were classified as 81 KS alone
of whom 29 (36%) had a complete response; and 19 KS
with opportunistic infections (OI), of whom 3 (16%)
with minimal oesophagal candidiasis had complete response. Data analysis was performed using the "Life Tables
and Survival Function" of the Biomedical Data Package.
Mortality data are presented as estimates of the survival distribution by the actuarial life table method.
RESULTS: Cumulative Probability of Survival (Conf. Int.)
1 YEAR 2 YEAR
KS Alone 75 (65-85) 56 (44-68)
KS+OI 26 ( 6-46)
All 66 (57-75) 49 (38-60)(expressed as %)
The crude case fatality rate was 47% for all patients,
and their median survival time was 691 days with a standard error (SE) of 230. For KS+OI, median survival was
251 days, SE 100. For KS alone, half the patients were
still alive at 1000 days, ie median survival was greater
than the period of follow-up.
CONCLUSION: In light of results obtained by interferon,
but also its side-effects, it is essential that studies
be set up to compare lengths of survival for the different treatment regimens available for AIDS-related
Kaposi's Sarcoma.

Notes:

3515 BETASERON INTERFEPON HAS IN VIVO ACTIVITY
AGAINST HUMAN IMTUNODEFICIENCY VIRUS (HIV)
AND AIDS PELATED KAPOSI'S SARCOMA (KS). S.A. MILES, E.
Cortes, S. Marcus, J. Carden, R. Rudd, and R.T. Mitsuyasu
Objective. A phase II efficacy and safety trial of
r-IFN-Bser in AIDS/KS patients.
Methods. We treated 21 patients (pts.) with AIDS/KS with
90 million units and 13 pts. with 180 million units subO
ao-F until disease progression or toxicity.
Results. Of 20 evaluable low dose pts., 10 had more than
75 pg. of HIV p24 antigen in their pre-treatment sera.
During treatment, 5 of the 10 had 50% decline or a fall
to zero in their serum HIV antigen, 1 remained stable
and 4 increased. HIV p24 antibody titers showed no
significant change in titers (2 dils.) during treatment.
PBM cell cocultures were initially positive in 9 pts.
Six became persistently negative and 3 remained positive.
Of 11 initially negative pts., 7 remained negative and 4
became positive. Clinically, 1 complete tumor response
was seen at week 8 (duration 52 wks.), 6 minor responses
within 4 wks, and 5 have stable disease with a median
duration of 32 wks. Median time to progression was 17
wks. Of 13 high dose pts., 4 progressed, 6 are stable
and 3 had local skin toxicity. Responses occurred in
pts. with low CD4 numbers, prior chemotherapy and a
previous history of PCP. There were no Ols during or
within four months off drug. Most CD4 numbers declined
or remained stable. Toxicity was mild and primarily nonhematologic (flu-like symptoms 30, renal 3, local skin 5).
Conclusion. rIFN-Bser has substantial in vivo anti--HIV
activity, some anti-tumor activity and is well tolerated
in a subset of patients with KS. Since no Ols were
seen, studies in ARC pts. are warranted.

3516 AIDS-ASSOCIATED KAPOSI'S SARCOMA:
TREATMENT WITH MODERATE DOSES OF
RECOMBINANT INTERFERON ALPHA-2A
Lvnda Kabbash. B. DeSalis, J. Shideler, N. Gilmore
Royal Victoria Hospital, McGill University, Montreal, Canada
Objective. To study the efficacy of a moderate dose of interferon alpha-2A (INF) in the treatment of Aids-Associated
Kaposi's Sarcoma (KS).
Methods. Twenty-five patients (mean age 39.4+9.5: Karnofsky
score 86.8+8.0: prior opportunistic infection 20% (5 of 25)) had
biopsy-proven KS. They received INF (10 X 106 U/m2) by the
intramuscular route with gradual escalation of doses to allow
tolerance. They were then maintained on 3 doses per week.
Results. Tumor response to INF is presented below:
Complete Partial Stable Disease
Tumor Burden N Response Response Disease Progression
Minimal 10 1 3 4 2
Moderate 12 1 2 4 5
Large 3 0 0 0 3
Totals 25 2(8%) 5(20%) 8(32%) 10(40%)
The mean duration of therapy was 7.0+6.2 months with the
shortest time being one month and the longest 19 months. Fever
occurred in 36.4% while asthenia was present in only 54.6%.
There was a significant (p<.001) 36% decrease in the leukocyte
count to 2.57+0.98 cells/mm3. The hemoglobin significantly
decreased 17% (p<.001) to 11.0+1.39 gm% while the platelets significantly (p<001) 32% decreased to 125+42 x103 /mm3. Liver
function tests significantly (p<.05) increased (highest value
Alk.Phos. 142+183; SGOT 89.9+84.7; LDH 264+106).
Conclusion. The overall effect of a moderate dose of INF with
a maintenance dose was to obtain a major response or disease
stabilization in 60% (18/25) of the patients. The dose was well
tolerated with an acceptable toxicity. This study indicates that
moderate doses of interferon can be used to control KS and
allow the use of other agents in combination.

B-10

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