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

Monday, July 8, 1996

Mo.A.522 - Mo.B. 112

specific CTLs recognizing a variety of different HIV epitopes.The analysis of the induced
cytokines demonstrated the stimulation of a ThI (ThO) pattern (IL-2, y1FN) rather than a
Th2 pattern of cytokine release.Type I VLPs stimulated gp120 specific CTLs without generating gp 120 specific antibodies. Conversely Type 2 VLP induced both arms of the immune
response resulting e.g. in high titers of envelope specific and neutralizing antibodies.
Adsorption of both VLP-types to alum suppressed the in vive priming of HIV specific CTLs.
Conclusion: Depending on the type and formulation of the VLP the proposed antigen
delivery system allows either the induction of a CTL response (i) in absence and (ii) presence of an envelope specific antibody response or (iii) the selective induction of a humoral
immune response.
Dr RalfWagner, Inst. of Medical Microbiology; 93042 Regensburg Tel [phone]
Fax:.[phone] E-mail: Ralf.Wagner)klinik.uni.rejensburg.de
Mo.A.522
INDUCTION OF HIV-I NEF SPECIFIC CTLs BY NEF EXPRESSING DNA VACCINE
Yusuke Asakura, Hamajima K, Fukushima J, Kaneko TiTsuji T, Sasaki 5, Bukawa H, Mohri H,
OhkuboT, Okuda K. Yokohama City UniversityYokohama,Japan
Objective: Recent studies have revealed the importance of HIV-I specific CTLs for preventing the establishment of infection and prolongation of entire clinical course in the infected
individuals. Among many epitopes of HIV I CTL determinants, Nef is thought to be one of
the essentials in preventing the establishment of infection. DNA vaccine is primarily intended to induce effective CTLs against immunized individuals.To determine whether pCMV
Nef DNA vaccine can induce CTLs against HIV I Nef was investigated.
Methods: HIV I Nef expressing plasmid DNA driven by cytomegalovirus promoter was
directly inoculated into gastrocnemius muscles of 4-week-old BALB/C mice. 4 weeks after
inoculation, each mice was sacrificed and CFL activities were evaluated by 5 I Cr releasing
assay to major- 3 Nef specific Tcell epitopes.
Results: HIV I Nef specific CTLs are clearly induced by pCMV Nef DNA vaccine.
Synthesized human T cell epitopes are confirmed to react with mouse H-2d gene products.
Conclusions: Direct inoculation of Nef expressing plasmid DNA has some advantages. First,
it can induce effective HIV-I Nef specific CTLs. Second, pCMV Nef has no pathogenesis, in
contrast to vaccinia virus induced Nef CTLs, for immunocompromised humans.These
results clearly show the advantages for effective HIV I vaccine development.
Y Asakura, 3 9 Fukuura Kanazawa ku,Yokohama 236, Japan Telephone: [phone]
Fax: [phone]
Mo.A.523
INDUCTION OF IMMUNE RESPONSES BY DNA OF HIV-I REGULATORY AND
STRUCTURAL GENES
Wahren Britta***, Hinkula, J*, Benthin, R*, Lundholm, P*, Svanholm, C*, Okuda, K***,
Schwar tz, cS v*Karolinskak Intitute, Stockholm; *Swedish Institute for Infectious Disease
Control, Stockholm, Sweden; * Yokohama City UniversityYokohama, Japan
Objectives: We aim to induce immunity to HIV by vaccination with regulatory and
structural genes.
Methods: The selected genes of HIV-I tat, nef, rev, envelope gp 160 and nucleoprotein were
transactivated by the human cytomegalovirus promoter IE and named pHCMVsrev,
pHSCVtat, pHCMVnef, pCMVgp 160 and pCMVp37gag. Intramuscular, intradermal, intranasal
and oral administrations of plasmid DNA were performed. 150 immunocompetent mice of
the strains dba/2, Balb/c, and CBA, as well as mice transgenic for HLA A-2 were immunized.
Immunization on a human background was performed in severe immunodeficient (SCID)
C.B.-17 mice repopulated with human lymphoid cells of HLAA-2 donors.
Results: Immnunocompetent mice reacted with humoral and cellular responses to HIV regulatory and structural gene products. Specific IgM and IgG responses during immunization
were noted in almost all animals after 2-3 inorculations.The development of specific IgG and
IgA increased with repeated DNA doses. In mice without detectable antibody in vitro cultivation of B -cells with the respective antigen gave a synthesis of specific IgG.Tcell proliferative responses and delayed type hypersensitivity developed in half of the animals. Human
lymphopoietic tissue in SCID mice responded to vaccination with HIV regulatory genes by
S specific B-cell antibody synthesis and in a few cases with T-cell proliferative responses.
Conclusions: Responses to the regulatory gene products gave higher antibody titers than
_ for the structural proteins and conferred strong cellular reactivities. Primary specific IgM
> responses were obtained in immunodeficient animals.With comparable gene dosing, intraD dermal administration gave strong and long-lasting Tcell responses while intramuscular injec0
u tion gave better antibody responses. Intranasal administration gave strikingly high IgA and
C IgG responses. In order to obtain complete antiviral resistance, genes for regulatory and
> structural proteins may be combined.
Prof. Britta Wahren, MtC, Karolinska Institute, Swedish Institute for Infectious Disease
Q Control, S -105 2I STOCKHOLM, Sweden- Iel: +46-8-735 I 300, Fax: [phone]
S Mo.B.IIO
O PERSISTENT ORAL ULCERS IN HIV INFECTION: CLINICOPATHOLOGIC
o CORRELATION WITH SALIVARY HUMAN HERPESVIRUSES.
- Flaitz, Catherine 1.M, Boldogh I., Nichols, C.M. *, Albrecht,T.** *University ofTexasti Houston Health Science Center Dental Bisnch, * Bering Dental Clinic, Houston,TX;
a_ University of Texas Medical Branch, Galveston TX
c Objective: The purpose of this prospectue study was to characterize the clinical and
O histopathologic features of persistent oral ulcers (POUs) in HIV infection and correlate
these findings with vious huan herpesviruses (HHVs) in saliva.
r Methods: Sixty two consecutive HIV positive patients with POUs (duration > 2wks) flom
iO the Bering D/ental Cliiic were evi luated durini ag 2mo period. Epiderniologic data, CD4s,
-, risk factors, opportunistic infections, sexually transmitted diseases (STDs) and medications
sO
c were recorded. POUs were biopsed aid prepared for routine microscopic examination
_~ (H&E, PAS, Gram stains, and immunocytochemical stains for CMV and HSV antigens)
" Whole salva (2ml cryopr-eserved) was analyzed for CMV, HSV I/2, EBV, HHV6A/6B, HHV
-- 7 and HHV 8 usin g polymerase chain reaction (PCR).
X Results: POUs were diagnosed in 62 patients (53M:9F: 35W, 16B, II H) with a mean age of
38yrs and a mean CD i toulto 62/ens3, Medications included antiretrovirals (57%) and
16 antiherpetics (50%). Host pti ts (T 7 ) admited to at leist one STD. Concurrent genital

and gastrointestinal ulcers of unknown etiology were self-reported in 30% of patients. Mean
lesion duration was 6 wks with ian average of 2 ulcers per patient. Most common lesion
sites were buccal/labial mucosa (27%/), tongue/floor of mouth (26%), and gingiva (22%).
Histopathologic diagnoses included nonspecfic/aphthous ulcer in 37%; CMV in 27%;
CMV/HSV in 8%; HSV alone in 3%; necrotizing stomatitis ini 18%; histoplasmosis in 5%; and
bacillary angiomatosis in 2%. Multiple H I1Vs were detected in the saliva of 87% of the
patients (EBV 76%; CMV 71%; HSV -I/2 20%; IHV-6A/6B 38%; HHV-7 49%: HHV-8 30%).
Conclusions: Persistent oral ulcers have a diverse and complex pathoetiology in severely
immunosuppressed patients. Hepesviridae, in particular CMV, may be an important cause
of these debilitating ulcers. However, due to the presence of multiple HHVs in saliva,
regardless of the ulcerative disease, viral cultures may represent salivary contamination and
not the specific disease process. Biopsy of POUs for histopathologic and immunocytochemical evaluation is necessary to determine the etiologic agent and assist in therapeutic management of ulcerative disease. Supported by NIH-NIDR I-ROI -DE I1389
CM Flaitz,-Department of Stomatology Dental Branch, University ofTexas -Houston Hlth Sci
Ctr, 651I6 John Freeman Ave, HoustonTX 77030 Tel: [phone]; Fax [phone]
Mo.B. II
A LONG-TERM RANDOMIZED CONTROLLED CLINICAL TRIAL COMPARING
FLUCONAZOLE AND ITRACONAZOLE IN THE TREATMENT OF AIDS PATIENTS
WITH CANDIDA ESOPHAGITIS.
Giuseppe Barbaro, Grisorio, B.", Calderon,W.*, Di [Lorenzo, G., Giorgio Barbarini*. On
behalf of THE CANDIDA ESOPHAGITIS MULTICENTER ITALIAN STUDY (C.E.M.I.S.)
GROUP Department of Emergency Medicine, University La Sapienza" Rome, Italy, *
Department of Infectious Diseases IRCCS, Policlinico S.Matteo University of Pavia, Italy
Division of Infectious Diseases OO.RR. Foggia, Italy.
Introduction: Contrasting opinions exist about the pharmacolo gical treatment of
esophageal candidiasis in HIV positive patients and little information is actually available
regarding the response of Candida esopha gitis to antifungal therapy Aim of the study has
been to assess the long term therapeutic efficacy of fluconazole and itraconazole in the
treatment of Candida esophagitis rin a selected population of AIDS patients.
Methods: Two thousand two hundred and thirteen HIV-positive patients have been selected
and double-blindly randomized to receive either fluconazole or itraconazole.The endoscopic and clinical response to treatment were then assessed at the end of follow-up (month 12).
Results: After 2 weeks of pharmacological treatment, endoscopic cure occurred in 81,2% of
patients treated with fluconazole and in 65,6% of patients treated with itraconazole (realtive
risk: 1.23; 95% CI: 1.08 1.33; p < 0.001). Clinical cure was observed in 81,5% of patients
treated with fluconazole and in 75,2% of patients treat ed with itiaconazole (realtive risk
1.08;:95% CI: 0,95- I.18; p < 0.001) A total of 2158 patients were clinically and endoscopically evaluable at week 5 and were considered for long term follow-up. At the end of fol
low-up, endoscopic and clinical cure were observed in 96,2% of patients treated with fluconazole in 96% of patients treated with ii0aconazole (relative risk: 1.00: 95% Cl: 0,87 1.08;
p - 0.816). By intention- to - treat analysi endoscopic and clinica cure were observed in
93,6% of patients treated with fluconazole in 933% of patients treated with itraconazole
(relative risk:.00; 95% Ct: 0,87-.08: p =0.857). Symptomat ic relapses of esophage tcandiasis were observed in 6% of fluconrzole-treated patients and 6,5o of itraconazole-terated
group (relative risk: 0,92;:95% CI: 0,79-0,99; p 0,650)
Conclusion: The results of this study have demonstrated that both fluconazole and itraconazole are provided with a good tong-term therapeutic efficacy in the treatment of
Candida esophagitis in AIDS patients. Fuconazole is associated with a higher rate of
endoscopy and clinical cure than itraconazole in short-term treatment.
Giorgio Barbarini Clinic of Infectious and Tropical Diseases IRCCS S. Matteo University of
Pavia 27100 PAVIA (ITALY) Telephone: [phone] Fax [phone]
Mo.B. I 12
FLUCONAZOLE RESISTANT MUCOSAL CANDIDIASIS IN ADVANCED HIV INFECTION
Fichtenbaum, Carl J, Koletar S, Yiannoutsos C, Chen D, Cohn S5, Pottage J. Powderly W for
the ACTG 816 Team.
Objective: To define the epidemiology of fluconazole resistant candidiasis in advanced
HIV infection.
Methods: ACTG 8 16 is a prospective, multicenter observational study of the incidence, risk
factors and outcome of resistant mucosal candidiasis in HIV-infected persons with CD4+
lymphocyte counts < 100 cells/mm3. Patients were enrolled at 20 sites and were evaluated
every 8 weeks for up to one year after the last patient was enrolled. Clinical failure to flu
conazole (FF) was defined as persistent mucosal candidiasis after 14 days of 2 200 mg/day
of fluconazole. At 7 sites, surveillance cultures from the mnouth and vagina were obtained
every 6 months (N=250). Isolates firom all persons with FF were collected. In-vitro fluconazole susceptibilities, reported as a minimum inhibitory concentration of 50% after 48 hours
of incubation (MIC50), were performed using a microtitoer assay modification of the proposed NCCLS anti fungal standards.
Results: 846 HIV infected persons were enrolled.The median CD4+ count at study entry
was 14.5 cells/mm3. At interim analysis, the annul incidence of- FF for oral candidiass was
5.8% with 472 person years of follow up. andid bics was recovered in 95% of FF
episodes and was the ony isolate in 86% of the fmilure episodes (N-2 I). AI FF patients had
an isolate with an MIC50 1 2 pg/ml
Conclusions: -he incidence of fluconazole resistant mucosal candidiasis is relatively low but
not insigniscant. C lticns coninues to be the primay etiology in the majority of cases
and higher in vitro fluconazole MIts correlate with clinical unresponsiveness.This informaIn wor hIIp define the optimal pproach to fungal i ophylaxis rn persons with adcmnced
HIV nfction
I)J Fichtenbum, 451 Forestpark Ave., Suite 304, St. Louis, MI 63 08
Telephone: [phone] Fix 3 I 31361 I53 ecil: fichtenbaum( tvisatwustl.edu