Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Track B: Clinical Science
Methods: In November 1992 we initiated an open randomized multicenter trial. Pts were
randomly assigned (stratified by CD4 count) to receive 10 MU (Group I) or 3 MU (Group
2) of IFN alpha 2b (Schering-Plough) administered daily for 3 months and thrice weekly
thereafter, associated with zidovudine 500 mg daily. Response and toxicity criteria were predefined.
Results: Forty-six pts were included (25 pts Gr.1, 21 pts G(r:2; 24 pts CD4<200, 22 pts
CD4>200). Eleven (24%) pts had prior AIDS and mean CD4 count was 206 (1 0-768)/ul.
27 (58.6%) pts had 10 or more skin lesions. No differences were found in baseline characteristics between Gr:I and Gr2. An intention to treat analysis showed progression rates at 3
months of I0% in pts with CD4>200 vs. 66.7% in pts with CD4<200 (p-=0.0001), and at 6
months of 33.3% vs. 79.2%, respectively (p=0.0004). Progression rates at 3 months were
52.4% in Gr.t vs. 30.4% in Gr.2 (p=0.220), and at 6 months were 60% in GI vs. 59. I% in
Gr.2 (p= 1.000). In pts with CD4>200 progression rates at 3 months were 22.2% (G I) vs.
0% (Gr.2) (p=0.189), and at 6 months 25% vs. 40% (p=0.638). No differences in suspension
due to intolerance were found between Gr:l and Gr.2, although a trend towards higher
toxicity (44.4% vs. 15.4%, p=0.178) was observed in pts in Gr:I with CD4>200.
Conclusions: As previously reported, IFN plus ZDV is more useful in pts with KS and
CD4>200. A daily dose of 3 MU seems to be equally effective as a higher dose and has the
advantage of lower cost.
D. Podzamczer. Infectious Disease Service. Ciutat Sanitaria de Bellvitge. LHospitalet.
Barcelona. Spain Fax [phone]
Tu.B.2223
HIV VIREMIA DURING ANTITUMORAL CHEMOTHERAPY
Rutschmann, Olivier T Lorenzi P, Pechere M, Krischer J, Rosay A, Hulliger S,Yerly S, Perrin L,
Hirschel B. University Hospital, Geneva, Switzerland.
Objective: The incidence of malignancies (lymphomas, Kaposi sarcomas [KS]) is high in endstage HIV-infected patients and combined chemotherapies are often warranted.The effect
of these treatments on HIV virernia is unknown.The aim of this study is to determine the
impact of antitumoral chemotherapy on HIV viremia.
Methods: in a pilot study five patients with AIDS-related tumors (4 KS, I lymphoma) were
followed prospectively All received combined chemotherapy: Bleomycine (Day I and 8) +
Metothrexate (D I) + Vincristin (D I and 8) for KS and Vincristin (D I and 8) + Etoposide
(D I) + Mitoxanthrone (D I) + Prednisone (D I) for lymphomna. Sera were collected
before and one week after chemotherapyViremia levels were measured in batch using
Roche Amplicor method.
Results: viremria was stable in 2 patients with KS and a slight decrease in virenmia (<0.4 log
HIV RNA) was observed in 2 other patients with KS. A decrease of 0.42 log RNA occured
in the patient treated for lymphoma who had a concomitant increase in CD4 cell count
(277/mm3, 30% before; 739/mnm3, 53% after) and reduction in size of malignant lymph
nodes.
Conclusions: combined chemotherapy for Kaposi sarcoma does not seem to affect HIV
viremia.The slight decrease in HIV RNA and increase in CD4 cell count during lymphoma
treatment needs confirmation. More cases will be presented.
P Lorenzi, Div. of Infectious Diseases, HCU, CH- 121 I Geneva 14 Telephone: [phone]
12 Fax [phone]
Tu.B.2224
HUMAN HERPES VIRUS (HHV-8) DNA SEQUENCES IN CELL FREE PLASMA AND
MONONUCLEAR CELLS OF KAPOSI'S SARCOMA PATIENTS
Sosa Carlos* Harrington William**, Klaskala Winslow", Baum Wood Charles*. *Fogarty
International Training Program University of Miami; Dpt. Medicine University of Miami;
***Dpt. Neurology University of Miami
Objectives: To describe the natural history of HHV8 disease and define the types of blood
cells which harbor the virus.
Methods: Study subjects involved individuals infected with HHV-8. One (pt I) was an AIDS
case with cutaneous Kaposi's Sarcoma (KS), second (pt2) was an HIV I negative kidney
transplant patient undergoing immunosuppressive therapy. Seven blood samples were collected from ptl over a period of 3 months and 4 samples from pt 2 over a two month
period. DNA was extracted from peripheral blood mononuclear cells (PBMCs) and PCR
was performed to amplify a 233 bp product using conditions from the KS 330Bam
sequence published by Chang et al. Ultracentrifugation was carried out to pellet free viral
particles in the plasma. One aliquot of the pellet was treated with DNAse followed by
DNA extraction. PCR amplification of treated and untreated pellet material was subsequently performed.To determine which cell type(s) harbor HHV-8, an in situ hybridization
procedure using a digoxigenin labeled HHV-8 probe was used in fxed PBMCs.
Results: PBMCs from ptlI were positive at the first points but only weakly positive at time
point two. PCR signals were not detected at time point three and four: but were once sain
present at the next two time points. Pt2 PBMCs were positive initially but subsequently
became negative. In situ hybridization demonstrated, small population of mononuclear
cells in both samples which contained HHV 8 sequences. No signals were seen in normal
cells. Positive PGR results were obtained tn DNAse treated and untreated pellet samples,
indicating that HHV-8 signals must originate fom intact f-ee viral particles rather than fro
motan inaturout HHV 8 infected DNA.
Conclusions: Results suggest that HHV-8 can exist cel free in plasma and may through
viremc stages in both AIDS and non AIDS patients. The HHV 8 infects less than % of
mononuclear cells, suggestion that a narrow subset of PBMCs are susceptible to be infected
by HHV-8.
Carlos Sosa, University of Miami School of Medicine, Dpt. Epidemioogy & Public Health
(R669) PO. Box O6069, Miani, FL 33 01 Telephone: [phone]
Tu.B.2225

META-ANALYSIS OF ACYCLOVIR FOR KAPOSI'S SARCOMA PROPHYLAXIS
Lampirnen TM, Collier AC, Holmes KK,,+. Departments of *Epidemioloy: and
+Medicine; and the "*Center for AIDS and STDs, University of Washington, Seattle,
Washington, USA
Background: The association of human herpesvirus type 8 with Kaposi s sarcoma (KS)
prompted us to assess the potential effect of acyclovir (ACV) in reducing thle incidence of

Tu.B.2223 - Tu.B.2227
epidemic KS. Since observational data can yield biased estimates of therapeutic efficacy, we
conducted a meta-analysis of randomized controlled trials (RCTs)
Objective: To obtain a valid estimate of the relative risk (RR) for KS among HIV+ individuals
prescribed zidovudine (ZDV) plus ACV compared to ZDV plus placebo.
Methods: We identified published and unpublished RCTs by professional database searches
(AIDSLINE, AIDSTRIALS, Dissertation Abstracts, EMBASE, MEDLINE). review of bibliographies, and consultation with experts. Unpublished data were obtained fi om principa investigators and trial sponsors A fixed effects model was used to compute a summary RR estimate and 95% confidence interval.
Results: Five eligible RCTs (with daily ACV doses of 3200 4800 mg) were identfied:
Trial a b c d e
N 265 67 230 693 306
KS Incidence 5% I% 7 I% 2
RR (CI) 2.1 (0.7 6.8) - 1.2 (0.4-3.1) 0.7 (0.2 2.4) 0.5 (0.1-2.6)
The summary RR across the trials was.I (0.6-2.0).
Conclusion: ACV administration in these daily doses was not associated with a clinically significant reduction in the incidence of epidemic KS.
TM. Lampinen, UW Dept of Epi, Box 357236, Seattle, WA 98195 USA Telephone: [phone] email: [email protected]
Tu.B.2226
AN UNUSUAL MANIFESTATION OF KAPOSI SARCOMA (KS) IN A PATIENT WITH
HIV DISEASE
Mullen, Michael P*, Cumaguns MR*, Abramovici L*, Friedman -Kien A"*. *Cabrini
Medical Center; New York, NY: 1 Hospital for joint Diseases, New York, NY; *New York
University Medical Center, NewYork, NY
Cutaneous vascular lesions associated with radiographic evidence of lytic bone lesions in
AIDS patients is usually suggestive of bacillary angiomratosis. Although rare, KS car also present with lytic bone lesions and should be considered in the differential diagnosis.
A 56 yo. homosexual ma le, known HIV positive since 1990, presented with progressively
worsening low back pain. His last CD4 count was less than 50 and he had a history of
Pneumocystis carinii pneumonia, thrush, CNST:xoplasmosis, and mucocutaneous KS which
was diagnosed one year previously A lumbosacral CT scan revealed multiple lytic lesions in
the vertebral bodies and iliac wings. A subsequent bone scan showed multiple areas of focal
increased uptake in the ribs, dorsal spine, lumbar spine, and pelvis compatible with osseous
metastatic disease. (Photos will be presented.) A chest radiograph at this time showed bilateral atelectatic changes and a rib series showed no osseous abnormalityThere were no
cutaneous lesions overlying the lytic bone lesions.The LDH and calcium levels were normal.
A biopsy of the right iliac wing revealed spindle cell proliferation, slit-like vascular spaces,
and extravasatedI erythrocytes compatible with KS.The patient received chemotherapy with
Bleomycin and Vincristine in addition to NSAIDS. Symptomatology improved and to date,
bone lesions have remained stable.
MP Mullen, Cabrini Medical Center; 227 F. 19th St., New York, NY 10003 Telephone: [phone] Fax: [phone]
Tu.B.2227
PRELIMINARY RESULTS WITH HUMAN CHORIONIC GONADOTROPIN IN
AIDS-RELATED KAPOSI'S SARCOMA.
Picard O, Hermans P*, Clumeck N", Gill P "*, Lunardi-skandarY"*, Gallo R*".
"Saint-Antoine, Paris; " C.H.U. Saint- Pierre, Brussels; '*K.Norris Hospital, Los Angeles,
I.H.V Baltimore.
In vitro and animal studies recently showed a potential benefit of human chorionic
gonadotropin (hCG), which appears to have a killing effect on tumor cells. Here we report
our preliminary results on 1 2 AIDS patients with KS who were given hCG (Preonyl ~,from
Organon) in a multicentre trial. All the patients were homosexual caucasian males (median
CD4+=50/ml from 5 to 180/mcl). Eight had previous history of opportunistic infections at
baseline and prior chemotherapy for KS was adlministered in 9.Half of the patients had
more than 20 cutaneous lesions with visceral involvement in three.Treatment consisted of4
intralesional(IL) injections of 500 IU of hCG in 4 index lesions once a week for 2 weeks followed by 2500 IU of hCG subcutaneously (SC), 5 days a week, for six additional weeks
then compassionately at the discretion of the irnvestigator:Tolerance was assessed weekly
and clinical evaluation of the index lesions performed at the end of therapy. Eight of the II
evaluable patients for efficacy showed a significant decrease of the tumor area of the index
lesions ranging from 10 to 40 I% from baseline valuesi (products of the biperpendicuilar
diameters), the lesions becoming more pale and flattened. By contrast with the local
response of the index lesions, new lesions appeared in 4 of the 8 s responders us One
patient with pulmonary KS dramatically improed, and two patents are on therapy with
hCG more than one year after their enrolment ( 50001U tiw,SC) Three patientos failed to
respond One patient discontinuated after 2 weeks for severe cholestasis likely due to concomitant antituberculous therapy.Two others pematurely interrupted the treatment mter I
month for personal reasons, not related to the hCG therapy In 6 patients an increased
appetite was reported associated in 3 with a weight gain of 2 to 12 pounds. Local pan during t1e intralesional injection was commonly observed in t patients as well as 4 perilesional
redness and pruritis.Two patients complained of transient gynecomastia. No other adverse
reasion were noted durin the subcutaneous therapy and the CD4+ increased in 2
patients (22 and 60 respectively) without any chan e in antiviral therapy From our prelimi
nary daa we suggest that: Imlocal injections of Pregnyl@ induced a tumor size reduction of
10-40% in 72% of our patients.The exact mechanism of action remains to be determined;
2) tolerance was excellent wit an associated increased appetite; 3) the systemic SC route
of 2500 IU/day ppers to be isappropr5ate to control KS diseae progression r is
should be initiated to determine th ml doses for systemic approches: 4) hCG could
have indirect beneit on the immune systes whinh would nrt further analysis.

Odile Picard, Medecine Interne, Prof. Imbert, Assistance Publique-Hpitaux de Pans, StAntoine, 18,t Rue du Faubourg Saint-Antoine, 7557 1 Paris Cedex 2, France Tel.:
33.1/49.28.23.88i Fax: 33.1/'t9.28.25.70.

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