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

12th World AIDS Conference

Abstracts 22273-22277 317

performed using the two-tailed Fisher exact test (p value) with Yates correction
(pc).
Results: The frequency of HLA antigens and alleles, and statistical analysis of
data are shown in the Table:

HLA
A31
B35
B41
DR12
DQ6

CMV-R (%)
19
44
12
19
6

Controls (%) p
1.0 0.002
19 0.026
1.0 0.018
4 0.034
52 0.024

pc
0.0001
0.04
0.006
0.039
0.047

RR
16.1
2.3
16.1
5.2
0.19

FE(%)
24
11
15

RR = Relative Risk; FE = Etiologic Fraction; FP = Preventive Fraction
Conclusions: HLA class I antigens (-A31, -B35, and -B41) and the HLA class
II allele HLA-DR12 were associated with susceptibility to, whereas HLA-DQ6
allele was associated with protection against the development of CMV-R in
Brazilians. The results here reported support the role of HLA molecules in the
susceptibility/protection to CMV-R.
22273 Extensive optic disc neovascularization in a patient with
cytomegalovirus retinitis
Daneil Colombero, E. Teicher, S. Lupo, M.C. Novo, P. Barbieri. Caici Rosario,
1215, 2000 Rosario, Argentina
Objective: To present an atypical complication of cytomegalovirus (CMV) retinitis
in a patient with a bilateral, rapidly progressive involvement.
Case Presentation: A 37-year-old man was found to be seropositive for human immunodeficiency virus in 1988. He later developed esophageal candidiasis,
fellowed by Tuberculosis in 1996. In November 1996 he complained of decreased
bilateral vision and photopsia. CD4 cells count at this moment was 39//,L, and
V.L. was 223.800 copies/ml. Visual acuity was counting fingers in both eyes.
Ophthalmoscopic examination revealed bilateral rapidly progressive CMV retinitis
involving both optic nerves, which resolved with induction levels of intravenous
ganciclovir therapy. PCR on aqueous humor was positive for CMV and negative
for herpes virus, toxoplasma gondii and mycobacterium tuberculosis.
Six months after initial examination, with the patient still maintained on a ganciclovir regimen, a tuft of neovascularization overlying the optic disc was noted in
the left eye.
Visual acuity remained counting fingers in both eyes and no signs of reactivation were present. Optic disc neovascularization increased its size during the
next two months, but remains stable after seven months of follow up.
Conclusion: Optic disc neovascularization is a rare ocular condition in patients
with large areas of capillary nonperfusion due to CMV retinitis.
22274 1 HBS antigen in children with suspicion of HIV infection
Boubacar Nacro1, B. Dao2, H. Dahourou2, P. Bonkoungou2, FR. Tall2. 1BP 1450
Bobo Dioulasso; 2CHNSS BP 676 Bobo Dioulasso, Burkina Faso
Objective: to evaluate the prevalence of HBs Antigen in children with suspicion
of HIV infection
Methods: One hundred and three children and there mothers were included
in this study. For the children, the following inclusion criteria were used: born
from HIV+ mother, clinical signs of likehood of HIV infection like severe malnutrition, persistent oral candidiasis, chronic cough with interstitial pneumopathy
at radiography, chronic diarrhea an lymphadenopathies. After informed consent
of mothers, screening for HIV (Genelavia Mixt, sanofi) and HBs antigen was
performed in both children and mothers.
Results: the mean age of the children and their mothers was respectively 2
and 26 years. The prevalence of HBs antigen was 39.8% in children and 35% in
their mothers. HIV Elisa test was positive in 57% of the children and 63.1% in their
mothers. There was a correlation between the portage of HBs antigen in children
up to 2 years old and in their mothers (p = 0.0072, X2 = 7; RR = 2.54; 1.35 < RR
< 4.79). The same trend was observed for the portage of HBs antigen and HIV
Elisa positive in children (p = 0.04, X2 = 4; RR = 1.46; 1.06 < RR < 2.02). There
was a correlation between HIV Elisa + in mothers and in their children (p = 0; X2
= 57; RR = 4.64; 2.58 < RR < 8.33).
Conclusion: the following data strongly sugest a mother-to-child transmission
of both HBs antigen and HIV in the study population. There is a need to promote
antenal screening for HIV and immunization against hepatitis B in newborns in
our setting.
617*/22275 Effect of highly active antiretroviral treatment
(HAART) in patients with AIDS-associated Kaposi's
sarcoma (KS)
Sara Santambrogio, A.L. Ridolfo, N. Tosca, M. Galli, C. Parravicini,
M. Corbellino. University of Milan Milan, Italy
Background: Antiretroviral regimens that include a protease inhibitor have dramatically decreased the incidence of several AIDS-related opportunistic disorders.
Anedoctal reports suggest an analogous pattern for AIDS-KS. Aim of our study
was to evaluate the effect of HAART on the clinical course of KS and the clinical value of KS-associated herpes virus (KSHV) viral load in peripheral blood
mononuclear cells.
Methods: A pilot study was begun in 9 patients (pts) with AIDS-KS (NYU
Staging System: stages I-II). None of the subjects had been previously treated

with antineoplastic drugs or HAART. At enrollment, all patients were evaluated for
KSHV lytic and latency associated antibodies in serum, CD4 T cell counts, HIVRNA plasma viremia by branched DNA and KSHV DNA sequences in PBMCs by
semi-quantitative polymerase chain reaction (PCR). In all cases, HAART included
two reverse trascriptase inhibitors and indinavir. No concomitant treatment for KS
was administered during the study.
Results: 8 pts (7 males and 1 female), with a median age of 30 yrs (range
22-54) were consecutively enrolled. At baseline, the median CD4 cell count
was 57 cell/piL (range 2-786) and the median value of HIV-1 plasma RNA was
81,355 copies/mL (range <500-422,600). All pts were seropositive for KSHV
antibodies. The median follow-up was 11 months (range 9-13). The overall
clinical response rate was 87.5% (5 complete remissions-CR and 2 partial responses-PR);1 pt showed a clinical progression. All pts showed stable decrease
of HIV-RNA plasma viremia below 500 copies/mL (median reduction 2.175 logio,
range 0-2.9), and an increase of CD4 counts (median increase 81 cell// L, range
41-200). At baseline, PCR for KSHV DNA sequences in PBMCs was negative in
6/8 patients and remained undetectable during follow-up. All of them experienced
a clinical response (4 CR, 2 PR). The only 2 pts with detectable KSHV viremia
at enrollment presented a 2 loglo reduction in KSHV viral load under HAART.
Of these, 1 experienced a complete remission while the other showed clinical
progression which required systemic chemotherapy.
Conclusions: HAART exerts a beneficial effect on the clinical course of
AIDS-KS, probably through immune function restoration. In this study, clinical
improvement was observed in 100% of patients with undetectable KSHV viremia.
Monitoring of KSHV viral load in PBMCs may prove useful in the clincal managment of patients with AIDS-KS.
| 22276 | Anti-tumor activity of oral 9-cis-retinoic acid in AIDS
related Kaposi's sarcoma: AIDS Malignancy Consortium
Study 002
Steven Miles', B. Dezube2, J. Lee3, L. Kaplan4, J. Groopman2, W. Saville5,
D. Scadden6. 1UCLA Care Center, Rm BH12C CHS Los Angeles, CA
90095-1793; 2BI-Deaconess Hospital, Boston MA; 3UAB, Birmingham AL;
4 UCSF SF General Hospital, San Francisco CA; sUCSD, San Diego CA;
6Harvard, Boston MA, USA
Objectives: To determine the safety, tolerance and efficacy of oral 9-cis-retinoic
acid (LGD 1057) capsules in patients with AIDS-Kaposi's sarcoma.
Design: Phase II, open label clinical trial in a multi-center network using a
modified Simon two-stage method.
Methods: Patients received 60 Mg/M2 of LGD1057 each afternoon up to a
maximum of 100 mg/M2 as tolerated. Patients were seen biweekly and evaluated
at 16 weeks for tumor response using ACTG criteria. CD4 cell counts, HIV RNA,
adverse events, and quality of life data were analyzed for safety and tolerance.
Results: An interim analysis of 50 of 66 enrolled patients who met the study
criteria for response, developed toxicity requiring drug discontinuation or who had
received at least 16 weeks of therapy was performed. Most (78%) were white
males; median age was 38; and median CD4 count was 195 (range 6-784).
The majority (85%) was receiving at least 3 antiretroviral agents at study entry.
Most (70%) had received prior therapy (23 with local treatment and 22 with
systemic chemotherapy or immunotherapy). Partial responses were seen in 38%
(19), stable disease in 36% (18) and progressive disease in 12% (6) patients.
Responses occurred in patients with large tumor burden, low CD4 counts and/or
prior systemic chemotherapy. Studies of HIV RNA, RA receptor expression and
cytokine level are ongoing. Eleven (15) patients withdrew for adverse events. Ten
patients remained on a dose of 100 mg/M2 for up to 38 weeks. Grade 3 or 4
toxicities included headache (n = 13, 26%), elevated triglycerides (n = 5, 13%) and
skin (alopecia, desquamation, nail changes). Triglyceride and cholesterol levels
rose significantly during treatment peaking at week 10. Skin toxicity increased
over time despite topical vitamin E therapy.
Conclusion: Oral 9-cis-retinoic acid (LGD1057) is an active anti-tumor agent
in AIDS related Kaposi's sarcoma with a response rate of greater than 30% (C.I.
22-55%). More clinical studies focusing on methods to improve tolerance and
identify predictors of response are warranted.
618*/22277 Topical 9-cis-Retinoic acid (Panretin ) gel as
treatment of cutaneous AIDS-related Kaposi's
sarcoma: Interim results of an international,
placebo-controlled trial (ALRT 1057-503)
Neil Bodsworth. On Behalf of the International Panretin KS Study Group
International; Taylor Square Private Clinic, 302 Bourke Street Darlinghurst NSW
2010, Australia
Objective: To assess the efficacy and safety of Panretin 0.1% gel (9-cis-retinoic;
Allergan Inc and Ligand Pharmaceuticals Inc.) as treatment of AIDS-related
cutaneous Kaposis sarcoma (KS) lesions.
Method: HIV-infected persons with >3 biopsy confirmed, cutaneous KS lesions and with no prior local treatment to indicator lesions nor prior systemic
retinoids were eligible for this placebo-controlled, randomised (1:1 ratio), dou
ble-blind study of 0.1% 9-cis-retinoic acid gel. Gel or matching placebo vehicle
was applied to lesions twice daily for 12-weeks or until lesions progressed (PD).
Enrolment was at 17 sites in Australia, US and Europe. Response was assessed by measurement of lesions according to the ACTG KS criteria as applied
to topical therapy for complete clinical response (CCR), partial response (PR)
and progressive disease (PD) and with supportive photography. Target enrol