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

12th World AIDS Conference

Abstracts 22243-22247 311

117* /22243 Rapidly evolving hepatitis C virus infection in HIV
coinfected patients treated with HAART
Gilles Pialoux1, A. Landau2, M. Eliaszewicz3, S. Pol4, F. Carnot5, J.D. Poveda3,
B. Dupont3. 1209 Rue De Vaugirard 75015, Paris; 2Broussais Hospital, Paris,
3Pasteur Hospital, Paris; 4Necker Hospital, Paris; 5Laennec Hospital, Paris,
France
Objectives: to assess the effect of immune restoration during HAART therapy including inhibitor of protease on HCV infection. Virological and histological
findings.
Design: Prospective study.
Methods: HCV and HIV RNA levels were measured by PCR (Roche assays)
3 months before initiating HAART and 6 months after as well as liver functions
tests, CD4/CD8 count and liver biopsy (Knodell score). Ten patients on 120
HIV co-infected patients were selected when rapidly evolving HCV infection were
suspected because of an unexplained elevation of alanine aminotranferase (ALT).
Results: The mean ALT were 57: 20 before HAART therapy compared with
137 1 52 after (p - 0.05). The table shows median values of HCV and HIV viral
load, mean CD4 and CD8 lymphocytes count and mean total Knodell score. We
observed in these 10 cases, in the absence of other cause of liver deterioration,
impairment of liver lesions chronologically paralleled increased in CD4 and CD8
cells count.
Refore HAART After HAART

ophthalmic examinations were done prior to each injection, and all injections
were administered using the same standard technique. Unscheduled evaluations
were also done in response to subjective complaints or objective findings. 91
patients (117 eyes) were treated with 3.0 mg/ml fomivirsen and 228 patients (296
eyes) were treated with 6.6 mg/ml of fomivirsen. Many eyes had previously failed
several other therapies for CMVR. The total number of doses per patient ranged
from 1 to >30, with length of time on drug ranging from 1 to >730 days.
Results: The more frequently reported ocular adverse events include (low
dose vs. high dose): transient elevation of intraocular pressure, 10% vs 18%; mild
to moderate anterior chamber inflammation, 9% vs 16%; vitritis, 3% vs 12%. A
retinal detachment incidence of 3% vs 10% was reported. Intraocular pressure
elevations were managed with appropriate anti-glaucoma medications and occasionally with anterior chamber paracentesis. Inflammatory events were managed
with topical steroidal and non-steroidal anti-inflammatory agents.
Conclusions: Fomivirsen has a clinically acceptable safety profile when used
at either dosing level. The most frequently occurring ocular side effects were
transient and managed with topical medications. The retinal detachment rate is
below that represented for the natural history of CMVR and for other forms of
local ocular therapy.
S22246 1A comparison of four assays for CMV viremia in patients
with AIDS at risk for CMV end-organ disease
David Wohl1, C. Noetzel', S.A. Fiscus', T. Alcorn', S.M. Scheiber2, J. Handy',
C. Van der Horst'. ' University of North Carolina, 547 Burnett-Womack Bldg, CB
#7030, Chaper Hill, NC 27599; 20rganon Teknika, Durham, NC, USA
Background: Detection of CMV DNA by PCR has been demonstrated to predict
CMV disease in studies performed prior to the advent of HAART. We prospectively examined blood specimens from 78 patients enrolled 9/97 to present in the
University of North Carolina CMV Epidemiology Study for CMV viremia using 4
assays for CMV detection.
Methods: Blood was collected every 1-3 months from patients CMV IgG+ and
with a CD4 count currently <200/mm3 or at one time <50/mm3. Roche plasma
CMV DNA PCR, Digene Hybrid Capture, Organon Teknika NucliSens CMV and
CMV Antigen (pp65) were performed. Indirect ophthalmoscopy was performed
approximately every 3 months. Median follow-up on study is 2 months.
Results: 128 specimens from 78 patients were collected of which 18 (14%)
specimens from 13 (17%) subjects had detectable CMV by one or more of the
assays. CMV was only detected by CMV DNA PCR and/or Hybrid Capture. No
specimen had CMV detected by either the CMV Antigen or NucliSens. In only
2 patients did CMV DNA PCR and Hybrid Capture simultaneously detect CMV
viremia. One patient has developed CMV retinitis and had CMV DNAemia detected by PCR 4 months prior to this diagnosis. 68% of subjects are receiving
HIV-1 protease inhibitors. HIV RNA PCR and CD4 characteristics for subjects
with CMV detected (+) and not detected (-) are presented below:

CD4
CD8
HCV viremia
HIV viremia
Total Knodell score

108 i 46
476 80
27 6
643 232
5.5

248 + 82a
1103 1 430a
59 + 7a
3 11.5a
11.5a

a p 0.05, when compared to baseline
Conclusion: This study suggests that dramatic improvement in the immune
status under HAART may enhanced the occurrence of severe HCV infection in
HIV coinfected patients.
22244 Long lasting remission of cytomegalovirus retinitis
(CMV-R) without maintenance therapy in HIV infected
patients
Cristina Tural1, J. Romeu,, G. Sireral, D. Andreui, L. Ruiz2, A. Arno2,
B. Clotet2. 'Hospital Universitari Germans Trias I Pujol, Unitat De Dia Vih Crta.
de Canyet, s/n-Edif. Maternal 2a Planta, Badalona; 2Fundacio Irsicaixa -
Retrovirology Lab., Badalona, Spain
Background: CMV retinitis is a frequent opportunistic infection which increases with severity of immununodeficiency. Immunological reconstitution can
be achieved after prolonged viral supression.
Objective: to evaluate if the association of clinical, immunological and virological response to HAART could aid the decission of stopping secondary prophylaxis
(SP) in HIV patients with previous diagnosis of CMV-R.
Patients and Methods: HAART was offered to a cohort of 16 patients (p) on
CMV SP because of a previous diagnosis of CMV-R. The SP was planned to witheld if they achieved the following criteria: stable CD4 cell count >150 cell/mm3,
undetectable plasma HIV-1 RNA (VL) (Amplicor Roche, limit of detection <200
copies/ml), negative qualitative plasma CMV-PCR and no new episodes of CMV-R
at 3 months (m) of starting HAART. Ophtalmologic evaluations (OE) were conducted weekly for the first m and monthly subsequently; CD4 cell count, VL and
qualitative plasma CMV-PCR were performed every 3 m. Results: ten patients
fulfil the criteria but 3 refused to withold SP. SP was stopped in the remaining 7
patients (6 males, 1 woman, median CD4 cell count and HIV VL at the time of the
diagnosis of CMV-R: 28 cell/mm3, and 125,920 copies/ml respectively, median
time on CMV SP: 11 m). During a median follow-up period of 14 months (range
17-12), no new episodes of CMV-R or new AIDS events have been reported. At
the first year of follow-up the CD4 cell count is above 150 cell/mm3 in all p (median
increase of 237 cell/mm3, range 770-153 cell/mm3), HIV VL is undetectable and
qualitative plasma CMV-PCR remain negative.
Conclusions: This results do suggest that for selected patients with healed
CMV-R who have immunological and virological response to potent combination
antiretroviral therapy, temporary discontinuation of CMV SP may not result in
further retinal necrosis.
2245 Safety profile of low (3.0 mg/ml) and high (6.6 mg/ml)
dose fomivirsen for the treatment of CMV retinitis
Ronni M. Lieberman', L.R. Grillone2, J.W. Chandler2. 1944 Park Avenue, New
York, New York 10028; 2ISIS Pharmaceuticals, Carlsbad CA, USA
Objectives: To evaluate the safety of two different doses (3.0 mg/ml and 6.6
mg/ml) of the antisense oligonucleotide fomivirsen when used for the treatment
of cytomegalovirus retinitis (CMVR) in patients with AIDS.
Design: Safety data from 4 randomized controlled studies and 2 non-controlled
studies were pooled to determine the incidence of ocular adverse events following
intravitreal injections of fomivirsen.
Methods: Patients were enrolled in one of several clinical trials to evaluate
the safety and efficacy of 0.05 ml intravitreal injection of fomivirsen (low dose-3.0
mg/ml or high dose-6.6 mg/ml). Eyes received weekly intravitreal injections for
3 weeks, and were maintained on a bi-monthly or monthly schedule. Complete

Baseline HIV RNA
Copies/ml
(median)
32,273
34,373

Baseline CD4
Cells/mi
(median)
74
133

HIV RNA when
CMV detected
(median)
9,833

CD4 when
CMV detected
(median)
74

CMV
CMV
Conclusions: CMV DNA PCR and Hybrid Capture appear more sensitive
than Nuclisens and CMV Antigenemia for detection of CMV viremia. The clinical
implication of these findings will become evident when further clinical endpoints
develop. We will present follow-up data on these and the subsequent 150 subjects
enrolled.
S22247 Ganciclovir resistance in a prospective cohort of
HIV-infected patients with cytomegalovirus (CMV) retinitis
Christine Jacomet, C. Taslo, N. Aissa, N. Delphin, E. Wirbel, J.C. Nicolas,
W. Rozenbaum. Hopital Rothschild 33 BD DE Picpus 75012 Paris, France
Objective: To assess incidence of ganciclovir resistance and determine its consequences on the course of CMV disease in HIV-infected patients with CMV
retinitis, treated with ganciclovir.
Methods: Between June 1995 and July 1996, 30 HIV-1 infected patients with
CMV retinitis treated with ganciclovir (induction therapy 21 days followed by maintenance therapy) were prospectively recruited. Blood and urine samples were
collected before and after induction therapy and on a monthly basis thereafter
during routine medical and ophtalmological assessment and at any time CMV
disease progressed. CMV culture was performed on each sample. Susceptibility
testing by plaque induction assay and CMV UL97 and P54 genotyping were
performed for each isolated strain.
Results: During the follow-up period (580 d[95-850]), 25/30 patients had
CMV progression: 17 (68%) to CMV retinitis, 8 (32%) to neurologic involvement
and 5 (20%) to CMV disseminated disease. Before ganciclovir treatment, CMV
was recovered from 18/30 blood, 25/30 urine and 2/2 CSF samples. CMV was
subsequently recovered from 78/743 blood, 68/322 urine, 11/19 CSF, 5/6 bronchoalveolar liquid fluid, 1/1 colic biopsy and 1/8 bone marrow biopsy cultures.
126 CMV isolates were subcultured successfully and tested for susceptibility to
ganciclovir. No isolate obtained before GCV outset was resistant but 35 isolates
from 13 patients were phenotypically and genotypically resistant after a median
time of 177 days [31-538] of treatment. Time to occurrence of ganciclovir resistance was longer in patients with only retinitis (n = 4), compared to patients with