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

310 Abstracts 22239-22242

12th World AIDS Conference

Methods: 20 HIV and HCV infected patients were propectively followed. All
received HAART including RTIs in combination with indinavir (N = 8), ritonavir
(9), or ritonavir plus saquinavir (3). HCV and HIV RNA levels were determined
by Roche Amplicor'", before initiation of HAART, 6 weeks later and every 3-4
months thereafter. On-treatment were compared to baseline values (t-test).
Results:

Mean (~SE)

Baseline

Changes at
week 6 month 8 month 11 month 17
(N = 20) (N = 19) (N = 17) (N = 17)

Log copies/ml HCV RNA 5.3 (+0.2) +0.4 (~0.1)# -0.1 (~0.2)t +0.1 (~0.2): +0.04 (~0.3)t
Log copies/ml HIV RNA 5.0 (~0.1) -2.1 (~0.1)# -2.5 (~0.2)# -2.4 (~0.2)# -2.4 (~0.2)#
CD4 cells/mm3 81 (~22) +72 (~20)# +114 (~25)# +99 (~26)# 165 (~45)#
CD8 cells/mm3 479 (~69) +289 (~87)# +243 (~84)# +258 (+60)# +355 (~122)"
#p 0.05 compared to baseline values (t-test); tnot statistically different from baseline value
No significant change in ALT and AST levels was observed during long-term
follow-up.
Conclusions: These data confirm a moderate initial increase of HCV viremia
following introduction of HAART. Despite a persistant effect on HIV replication
and increase in CD4 and CD8 cell counts, HAART has no long-term beneficial
impact on HCV viremia. Thus, specific anti-HCV therapies are required to control
HCV infection.
S16*/22239 Recurrence of CMV disease in patients with a
history of CMV retinitis receiving protease inhibitors
Dominique Costagliola1, Dominique Salmon2, C. Michon3, C. Katlama4,
J.M. Lang5, J. Gerbe6. INSERM SC4 Faculte De Medecine St Antoine 27 Rue
Chaligny 75571 Paris Cedex 12; 2Hopital Cochin Paris; 3Hopital Louis Mourier;
4Hopital Pitie-Salpetriere Paris; 5Hopital de Strasbourg Strasbourg; 6Hopital
Bichat-Claude-Bernard Paris; CMV Clinical Epidemiology Group pf CISIH,
France
Objective: To study the impact of a protease inhibitor (PI) containing antiretroviral
regimen on recurrence rate and delay of recurrence of CMV disease, depending
on the CD4 level reached and on the discontinuation of anti-CMV treatment
Settings: French Clinical Epidemiology Database on HIV seropositive subjects
followed in hospitals (ongoing hospital cohort in 68 hospitals in France)
Methods: 243 patients with a first CMV retinitis episode between January,
1995 and March, 1997, subsequently treated by PI and followed for at least
three months after PI initiation were included in the study. Kaplan-Meier method
was used to estimate the delay of recurrence of CMV disease (whatever the
localisation). Mutivariate Cox proportional hazards model with time dependent
covariates (CD4 count above 100/mm3 and discontinuation of maintenance CMV
treatment) was used to analyse the data.
Results: Median follow-up duration were 4.8 months prior to PI and 10.2 post
PI. Median CD4 count at PI initiation was 14/mm3. The median time to recurrence
was estimated as 2.7 months prior to PI and 7.8 months post PI (p < 0.01).
Follow-up CD4 counts were available in 189 patients: CD4 counts remained
<100/mm3 in 127 patients, 103 (54%) who did not stopped CMV treatment and
24 (13%) who did; while CD4 counts increased above 100/mm3 in 62 patients,
39 (21%) who did not stopped CMV treatment and 23 (12%) who did. In the
multivariate Cox model, both covariates were found significant independently of
each other: the risk of recurrence was reduced in patients with a CD4 count
increasing above 100/mm3 during the follow-up (HR 0.48, 95% CI 0.26-0.89) and
in patients stopping CMV maintenance treatment (HR 0.41, 95% CI 0.20-0.84).
Conclusion: The median time between two recurrences was markedly increased in patients receiving PI. In this observational study, the risk of recurrence
is reduced in patients with CD4 count increasing above 100/mm3 under PI treatment and the discontinuation of maintenance CMV therapy in these patients does
not appear to increase the risk of CMV recurrence.
15*/22240 Evidence that HAART induced immune recovery
vitritis in CMV retinitis patients is immune mediated
Francesca Torriani, W. Freeman, D. Durand, M. Karavellas, R. Schrier. UCSD
Treatment Center, San Diego CA, 2760 Fifth Avenue Suite 300, San Diego
California 92103-6325, USA
Background and Objective: Clinically significant intraocular inflammation has
been described in AIDS patients (pts) with CMV retinitis (CMVR) and CD4 cell
rises following HAART (immune recovery vitritis). Manifestations include painless
decrease in visual acuity, floaters, vitritis, and cystoid macular edema and could
not be anatomically or causally related to CMVR. We compared in vitro proliferative responses in 7 CMVR pts to those of 6 pts with CMVR and sustained CD4
increases, but without immune recovery vitritis.
Methods: Proliferation assays were performed by standard methods by exposing PBMC to heat inactivated antigens (CMV, HSV, mumps, PHA, HIV peptides)
and values were expressed as stimulation indexes (SI).
Results: Vitritis pts, had CD4 > 70 after HAART for a median of 289 days
(range:45-526). Median ACD4 and ARNA were respectively +168 cells/mm3
(range: 126-878) and +0.5log10 copies/ml (range: -2.1 to +2.3). In 5/7 pts, CMV
MT had been stopped, while 2/7 were still receiving MT. 6/7 pts had healed CMVR
at the time of vitritis. Diagnosis of CMV re-activation and vitritis was simultaneous
for one pt, 45 days after responding to HAART with a CD4 increase from 55 to
154 cells/mm3. Pts with vitritis had higher CMV Sl's than controls.

Vitritis No Vitritis P-value
N 7 6
Mean CMV (SI) 14.6 5.2 0.04
Mean CD4 (cells/mm3 314 219 NS
Mean Plasma HIV RNA (log 10 copies/ml 3.7 4.2 NS
Conclusions: Immune recovery vitritis causes significant morbidity in patients
with healed CMV retinitis. These data suggest that the mechanism is immune
mediated and occurs in AIDS patients with clinical and immunological signs of
HAART induced immune recovery.
| 222411 Predictive value of cytomegalovirus (CMV)-PCR and
pp-65 for the detection of CMV-disease in AIDS-patients
in the era of HAART
Albrecht Stoehr1, T. Fenner2, C. Mocklinghoff3, T. Lorenzen1, A. Plettenberg1.
120099 Hamburg AK St. Georg LohmulenstraBe 5; 2Labor Dr Fenner Hamburg;
3Hoffmann-La Roche AG Grenzach, Germany
Background: Some trials have shown a high sensitivity, specificity and predictive
value of CMV-plasma-PCR for CMV-disease before the era of HAART. HAART
caused a significant decline of morbidity and mortality in AIDS-patients. We investigated the sensitivity, specificity and predictive value of pp-65 and CMV-PCR
in plasma and lymphocytes in the era of HAART.
Methods: We prospectively recruited pts. with a CD4 cell count between 25-75
c/pl. All pts. were seropositive for CMV IgG. Blood samples were obtained at
baseline, month 6, 9, 12, 15, 18, 21 and 24 and investigated by pp-65 antigenemia assay and PCR in plasma and lymphocytes. CMV-disease was diagnosed
by fundoscopy or endoscopy with tissue biopsies. All pts. received intensive
antiretroviral treatment including protease inhibitors if tolerable. Start of this trial
was february 1996.
Results: 49 pts. were recruited. Median follow up was 20 months (13-22).
Median CD4 cell count at baseline was 50 c//jl (0-110), HIV-PCR 110000 c/ml
(4000-600000). At time of evaluation CD4 cell count was 90 c//<l (30-270),
HIV-PCR 125000 c/ml (0->1 Mio.). 6 pts. developed CMV-disease (4 retinitis, 2
colitis), 1 pt. did not show up 6 month before development of CMV-retinitis. Of
these 5 had positive pp-65 and 4 positive PCR in plasma and lymphocytes. 25
pts. had virologic marker for CMV-disease, but no clinical manifestation (10 dead,
15 alive). 18 pts. showed neither a positive marker nor CMV-disease (7 dead, 11
alive). The sensitivity, specificity, positive predictive value and negative predictive
value for pp-65 was 100%, 72.1%, 29.5% and 100%; for PCR in plasma 80%,
74.5%, 26.7% and 96.7%; and for PCR in lymphocytes 80%, 67.4%, 22.2% and
93.5%.
Conclusions: The widespread use of highly active antiretroviral treatment has
reduced the morbidity and mortality of HIV-positive pts. by stabilising or improving
the immuno status. We realised a 79% decline of CMV-disease from 1995 to
1997 at our institution. At the same time the positive predictive value of pp 65
and CMV-PCR in plasma and lymphocytes declined, so these can actually not be
used as reliable indicator for CMV-disease.
20*/22242 Long-term response to interferon therapy in
HIV-infected patients with chronic hepatitis C
Javier Garcia-Samaniego1, Vincent Soriano2, Mayte Perez-Olmeda3,
Soledad Lopez-Calvo4, Angeles Castro4, Juan Gonzalez5, J. Gonzalez-Lahoz2.
1Liver Unit, Instituto Carlos III, Calle Sinesio Delgado 10, 28029-Madrid;
2lInfectious Diseases, Madrid; 3lnfectious Disease, ISC III, Madrid; 4Internal
Medicine, Hospital Canalejo, La Coruha; 5Internal Medicine, Hospital La Paz,
Madrid, Spain
Background: Patients with chronic hepatitis C (CHC) and concurrent HIV infection may have an accelerated course of liver disease. Alpha-IFN therapy in these
patients is still controversial. We investigated the long-term response (LTR) to
IFN therapy in HIV+ patients with CHC.
Methods: In September 1992, a multicenter, prospective trial began in Spain
addressing the efficacy and safety of alpha-IFN (INTRON A", 3MU tiw during 1
year) in HIV+ patients with CD4+ counts >200 cells//tl. One hundred and seven
patients (80 HIV+ and 27 HIV-) completed the trial. The mean histologic score
(~SD) was 7.9 - 3.6 (range 2-16). All patients had ALT greater than 2 times the
upper limit of normal for at least 1 year.
Results: End-treatment response (normal ALT) was observed in 26 (32.5%)
HIV-pos and 10 (37%) HIV-neg (p = Ns). Patients with a CD4+ count >500//1l
responded better than those more immunosupressed (42.2% vs 20%); p = 0.035).
The mean follow-up after the end of therapy was 3.4 ~ 2.2 years (range 1.7-5).
During the first 6 months of follow-up biochemical and virological relapse was
observed in 8 of 26 HIV+ and 2 of 9 HIV-neg (sustained response, SR: 22.5% and
25%, respectively; p = NS). At the end of follow-up 15 (83%) of 18 HIV+ patients
with SR remained with normal ALT levels. Serum HCV-RNA was persistently
undetectable in 12 (100%) of 12 HIV+ patients tested (one of them with mild ALT
increase). The mean CD4 count in these patients with LTR was 547 ~ 125 cells/

/pl (range 341-1,158).
Conclusions: Response rates to IFN therapy in CHC are similar in HIV-neg and
HIV+ patients with CD4+ counts >500/pl, as well as the rate of early relapses.
LTR is common in HIV+ patients with biochemical and virological response 6
months after the end of IFN treatment. These results are encouraging and suggest that HCV may be eradicated in HCV-HIV coinfected patients without severe
immnodeficiency and therapy should be recommended in them.