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

12th World AIDS Conference

Abstracts 32112-32116 543

Conclusions: The prevalence of positive HCV viraemia is more marked in
HIV positive than in HIV negative pts (95% vs 69%) and there are higher serum
levels of HCV-RNA in HIV positive pts; there is a slight difference between a Pis
containing regimen and a PIs not containing regimen in HIV positive pts regarding
either HCV viraemia and ALT values. Our results support the hypotesis that HIV
infection has only little effect on HCV disease and the use of PIs should not
influence the course of HCV infection.
32112 Different effects of disease progression and combination
antiretroviral therapy upon HIV mucosal genomic and
mRNA
Safak Reka1, D.P. Kotler2. 1SUNY HSC Brooklyn 450 Clarkson Ave. Box 1196
Brooklyn, NY 11203; 2St. Luke's-Roosevelt Hospital Center New York NY USA
Background: Intestinal mucosa may contain HIV mRNA in productively infected
cells as well as genomic RNA, the latter mainly found as virions trapped in immune
complexes in mucosal lymphoid follicles. The relative changes in these two forms
of HIV during disease progression and during antiretroviral theapy are uncertain.
We analyzed the relative amounts of HIV RNA in subjects at different disease
stages as well as during therapy with antiretroviral agents or placebo.
Methods: Cross sectional studies of rectal mucosa and plasma were performed in 54 subjects (9 with CD4 - 500, 32 with CD4 < 500, 12 with AIDS
by clinical criteria). Twenty subjects underwent repeat studies after antiretroviral
(10) or placebo (10) therapy. RT-PCR studies in mucosa were performed using
primers which distinguish genomic RNA (unspliced-US) from mRNA (multiply
spliced-MS).
Results: Mucosal log MS copy numbers varied significantly with disease stage
(p = 0.038), while log US and plasma RNA did not vary significantly with disease
stage. Log MS correlated significantly with log US (p < 0.001) and log plasma
RNA (p = 0.023), while log US did not correlate significantly with log plasma RNA.
Antiretroviral therapy (7 days) produced an average decrease of 1.4 log in MS
(p - 0.001) compared to a 0.65 log decrease in US (p = 0.005), and a 2.3 log
decrease in plasma RNA (p < 0.001). Placebo therapy did not affect mucosal or
plasma HIV RNA copy numbers.
Conclusion: HIV mRNA is more sensitive to change during disease progression and treatment than is HIV genomic RNA. The kinetics of decline in HIV RNA
is greater for mRNA than for genomic RNA. Mucosal HIV mRNA but not genomic
RNA correlates with plasma RNA.
S321131 HCV viral load in HCV-HIV-coinfected patients treated
with protease inhibitors
Cecile Goujard1, E. Marchandier2, S. Khelifa1, J.F. Delfraissy1, E. Dusaix2.
SHopital Bicetre 78 Rue Du Gal Leclerc, 94270 Kremlin Bicentre; 2Hopital Paul
Brousse-Virologie, Villejuif 94, France
Interactions between HCV and HIV, the role of immune response on HCV pathogenesis and HCV viral load remain uncertain. We started a cohort of HCV-HIV
coinfected patients treated with a multitherapy including at least one protease
inhibitor (PI), to evaluate the respective consequences of immune deficiency and
HIV replication on HCV viral load.
Patients Characteristics: Among 30 HCV-infected patients, 11 (6 men, 5
women) reached a follow-up of at least 6 months with a PI (ritonavir, indinavir,
saquinavir) in january 1998. The mode of contamination was IV drug use for 10
patients and transfusions for an hemophilic patient. 8 patients had CD4 cell count
below 200/mm3 and 3 patients above 200/mm3 at study entry. Liver, functions
(ALT), CD4, HIV-RNA, HCV-RNA were measured before treatment and then every
3 months.
Results: All the patients unless one were responder to antiretroviral treatment:
10/11 patients achieved an undectable HIV viral load (<200 copies/ml) and 9/11
an increased in CD4 cell count. In 5 patients presented with normal ALT at entry,
4 presented an increased of ALT and 1 was stable. 6 patients had elevated ALT,
with 2 increases, 1 stable and 3 improvements during PI treatment. HCV viral
load was high in the majority of cases and did not change on treatment.
Study is in progress for the others patients.
Conclusion: The evolution of HCV viral load did not correlate with the improvement of immunologic markers and HIV viral load in patients receiving
multitherapies with a protease inhibitor. Anti-HCV specific immune response
seems not to be restaured with a follow up of 6 to 12 months in our patients, or
would be inefficient to diminish HCV replication
32114 Liver histopathology and virological findings in patients
with concurrent chronic hepatitis C and HIV infection:
A case control study
Alain Landau1, G. Pialoux1, L. Aaron1, F. Carnot1, J.D. Poveda1, S. Pol2,
F. Dupont1. 1209 Rue De Vaugirard, Pasteur Hospital, 75015, Paris; 2Necker
Hospital Rue de Sevres, Paris, France

Objectives: To investigate the influence of HIV coinfection on HCV.
Design: Case-control study.
Methods: 64 patients with HIV and HCV coinfection under protease inhibitors
(Group 1), were compared to 69 patients with HCV infection (Group 2). HIVHCV and control patients were compared on age, duration of hepatitis, alcohol
daily intake, liver biopsy (Knodell score), alanine aminotransferase (ALT), serum
qualitative HCV RNA by PCR and HCV genotype.

Results: We found no difference for age, duration of hepatitis between our two
groups of patients. Genotype 3a was found in 62% and 55% respectively for group
1 and 2 (NS). All patients were HCV RNA positive. In coinfected patients mean
CD4 count was 89 ~ 32. Cirrhosis was significantly more marked in coinfected
patients (33%) compared to monoinfected patients (11%) (p < 0.05). Among
coinfected patients with cirrhosis, we found a significant lower rate of alcohol
consumption (35%) and activity of ALAT (71% with normal ALAT) compared to
monoinfected patients (respectively 75% and 25%) (p < 0.05).
Conclusions: HIV/HCV-coinfected patients lead to a significant higher rate of
cirrhosis compared to HCV-monoinfected. Alcohol consumption is not a major
cofactor of cirrhosis in the coinfected subgroup.The activity of ALT does not reflect
the activity of HCV in coinfected patients.
32115 Hepatitis C in HIV positive patients of recent diagnosis
Marcela Carin Agostini1, S. Lupo2, R. Bortolozzi2, J. Palazzi3, F. Sabato3,
A. Pelizzari3, E. Baravalle3. 1Rodriguez 1215 2000 Rosario; 2CAICI, Rosario;
31DEB, Rosario, Argentina
Introduction: The Hepatitis C is more frequent in HIV positive patients (Pts).
In previous studies made on 482 patients in our institution 56% presented HCV
positive serology against 1% of the general population.
Objectives: 1) To study the incidence of HCV in HIV positive Pts diagnosed
in the last year. 2) To describe the clinical epidemiological characteristics of
laboratory in this group and to evaluate the active replication in this population.
3) To investigate geno and serotypification.
Material and Methods: Researches on HIV positive Pts (diagnosed in our
centre) were made between 1996 and 1997. We made clinical record, hepatic
laboratory, Elisa and RIBA III for HCV, RT PCR Amplicor diagnostic (Roche) in
the HCV positive patients, MUREX HCV serotype 1-6 assay, ensimommunessay
to detect AC to serotypes 1-6 of the hepatitis C virus.
Results: From the 65 patients studied, 48 (74%) were male and 17 (26%)
were female, of average age: 33.4 years old. The contagion by heterosexual
relationships took place in 29 Pts (46%) by EV addiction in 18 Pts (28%) by
homo-bisexual relationships in 17 Pts (26%) and by multiple blood transfusion in
one Pt. AC and HCV were detected in 20 Pts (31%): 85% were male, 65% were
EV drug addicts and 36% were heterosexual. None of the patients presented
clinical evidence of hepatic insufficiency. 60% of the Pts presented hepatornegalia
and only one case revealed jaundice. 15% presented raising of hepatic enzymes
2.5 times above the normal level. The PCR for HCV was positive in 17 patient
85%. From 17 PCR positive patients, 13 belonged to serotype 1-genotype 1b, 3
belonged to serotype-genotype 3 and only I to both sero and genotypes.
Conclusion: 1) The incidence of HCV in HIV positive patients of recent diagnosis is smaller than in the historical series. 2) More than one third of the cases
belonged to heterosexual members of a population. 3) The hepatomegalia was
the most frequent clinical sign (65%). 4) Most of the patients showed evidence
of active replication in 85% by positive PCR. 5) The prevalence of serotype 1 -
genotype lb in relation to sero-genotype 3 is significant. 6) The coinfection of
both serotypes and genotypes was found in only one patient.
32116 1 Response and toxicity of interferon (IFN) c-2a treatment
in chronic hepatitis C (HCV) in HIV infected patients
Matthias Stoll1, H.L. Tillman2, G. Behrens1, E. Manck', M. Mendila1,
M.P. Manns2, R.E. Schmidt1. Medical School, Dept. Immunology 2Dept
Gstroenterology/Hepatology D-30623 Hannover, Gemany
Objectives: While hepatic dysfunction is a major cause of death in HIV/HCV
coinfection treatment with IFN is still discussed controversially in these patients
(pts).
Design: Prospective, open labelled, monocenter study.
Methods: Inclusion criteria: Age > 18 y., HIV+, chronic HCV-infection for >6
months confirmed by HCV-PCR, elevated ALT/AST, histological examination of
liver biopsy. Exclusion criteria: Karnofsky's score < = 50%, life expectancy <6
months, underlying diseases contraindicating for IFN treatment. Pts were treated
with 6 million units IFN oa-2a subcutanously three times/week up to 12 months.
Results: Patient's characteristics: 19 pts have been included since 8/96. [Age:
34 + 3 years; male/female: 12/7; risk factors: 16 IVDU, 2 hemophiliacs, 1 homosexual; CDC-stage: I (n = 6), II (n = 9), III (n = 4). Viral load (HIV-PCR: 43.685
copies ~ 89.978; HCV-PCR: 1, 10 Mio. copies ~ 1.03 Mio.).] The predominant
HCV-subtype was 1A/1B (53%). Response rates: Only 2 pts had complete responses (HCV-PCR negative, normalized liver enzymes) to IFN, 11/19 did not
respond. Toxicity: Reasons for early discontinuation: Toxicity (n = 3), intercurrent
diseases (n = 2). The study is ongoing in 6/19 pts. During IFN treatment 8/19 pts
experienced significant psychopathological alterations which afflict their social life
substantially.
Conclusion: The presented study suggests, that IFN-treatment of chronic
HCV hepatitis in HIV infected pts may be less effective and may cause more
neurotoxicity as compared to HIV-negative populations.

I32117 Intestinal enteropathogens as factor of reduced survival
in HIV positive patients
Walter Heise, K. Arasteh, W. Schmidt, S. Diecumann, U. Futh, G. Grosse,
M. Liage. Auguste-Victoria-Hospital 12157 Berlin, Germany
Purpose: Diarrhea and malabsorption are factors of reduced survival in AIDS