Abstract Book Vol. 2 [International Conference on AIDS (14th: 2002: Barcelona, Spain)]

88 Abstracts WePeB6039-WePeB6042

XIV International AIDS Conference

Presenting author: Javier Murillas, Hospital Clinic, Calle Villaroel 170,
Barcelona, Spain, Tel.: [phone], E-mail: [email protected]
WePeB6039 Evolution of HCV quasi-species after initiation of
HAART in HIV-1 co-infected patients
J. Babik1, M. Holodniy2. 1Stanford University, Stanford, CA, United States; 2VA
Palo Alto Health Care System, aids research center, 3801 miranda ave. (132),
Palo Alto, CA, United States
Introduction: HCV viral load (VL) and genetic heterogeneity may indicate the
severity of HCV disease and likelihood of treatment response for HCV disease.
Studies have documented changes in HCV quasi-species during interferon treatment. There have been no conclusive studies in HIV co-infected patients on the
effect of anti-HIV therapy and immune restoration on this parameter of HCV infection. We therefore studied the effect of HAART on HCV genetic diversity in
HCV/HIV co-infected patients.
Methods: Three cohorts of HIV/HCV co-infected patients were identified: those
who initiated HAART (H); those on HAART with an HIV VL < 50/mi for > 1 yr
(S); and HIV drug naive who remained off HIV therapy (C); Serum from 4 time
points were collected at baseline and over a 6 month period. HIV and HCV viral
loads were performed using the Bayer Versant 3.0 assays. HCV genotypes were
obtained by LiPA. Serum HCV RNA was purified and RT-PCR of the E2 HVR1
gene performed. Amplicons were cloned into a TA vector, transformed in bacteria
and 10 clones from each time point were sequenced, aligned and analyzed for
genetic complexity and diversity scores.
Results: 17 subjects (7 H, 6 S and 4 C) were included for study. HIV and HCV
VL were significantly reduced and increased respectively in H compared to S and
C. Despite increases in CD4 and CD8 counts in H, these numbers and CD4/CD8
ratio remained greater in S. The relative change over time in clone #, entropy, diversity and Ka/Ks favored the S group. The mean values for these variables over
time were significantly higher in the S group compared to H and C. HCV genotype
did not appear to affect the above changes.
Conclusions: HCV quasi-species complexity and diversity appears greater in
those on stable HAART and who have higher CD4/CD8 counts. Higher T cell
counts are probably reflective of increased immunologic pressure leading to virologic escape and evolving increased diversity. HAART can impact HCV diversity
in co-infected patients.
Presenting author: mark holodniy, aids research center, 3801 miranda ave.
(132), Palo Alto, CA, United States, Tel.: [phone], Fax: [phone],
E-mail: [email protected]
WePeB6040 ALT does not predict hepatic fibrosis in HIV/HCV
co-infected patients on antiretroviral therapy
P Kouvatsos1, R.E. Doerfler2, W.C. Woodward2. 1Albright College, 145 North
5th St, Suite 205, Reading, PA 19601, United States; 2Bornemann Internal
Medicine, Reading, United States
Background: Liver disease is a major cause of morbidity and mortality in patients
co-infected with HIV and Hepatitis C (HCV). Antiretroviral (ARV) hepatotoxicity
may contibute to such toxicity. While studies have focused on transaminitis as a
marker for ARV hepatotoxicity, this may not be an adequate surrogate for the progression of liver disease and hepatic fibrosis. Liver biopsy (LBx) may play a key
role in determining treatment.
Methods: A retrospective review of 62 urban HIV/HCV+ patients who had LBx
over the previous 3 to 4 years due to elevated HCV-RNA (quantitative). Nine were
excluded from analysis for various reasons. Data abstracted: patient demographics, ALT, ARV therapy history before LBx, LBx grade and stage (Scheuer), CD4,
and HIV RNA.
Results: Primary mode of HCV acquisition: IVDU/sex with IVDU. Of 53 subjects
evaluated: 35.8% were female, 41.5% were black, and 37.7% Hispanic. Alcohol
consumption could not be reliably quantified. None had ACTG Grade 3 or 4 elevation of ALT a mean of 35 days before LBx. 11/53 (20.8%) had Stage 3 or 4
fibrosis: 3 females, 3 blacks, 5 Hispanics and 3 whites. All had been on ARVs
for a mean of > 12 months before LBx. Stage 3 or 4 fibrosis was found in: 7 of
31(22.6%) on PIs vs. 3 of 19(15.8%) on NNRTIs; 2 of 28(7.1%) on AZT (95% Cl:
0.0, 16.7) vs 9 of 25(36%) on d4T(95% Cl: 17.2, 54.8). One subject progressed
from Stage 3 to 4 with serial biopsy, while ALT decreased.
Conclusions: ALT was not clinically useful in predicting staging of liver biopsy in
this cohort of HIV/HCV co-infected patients. Fibrosis stage did not differ between
PI vs. NNRTI regimens but may differ AZT vs. d4T. Despite the limitations of a
retrospective analysis, this study suggests LBx gives more reliable staging data
than following transaminases, in HIV/HCV+ patients. Serial LBx may be useful as
well, and may be the only way to adequately follow the impact of ARVs on the
progression of liver disease due to HCV.
Presenting author: William Woodward, 145 North 5th St, Suite 205, Reading,
PA 19601, United States, Tel.: [phone], Fax: [phone], E-mail:

[email protected]

WePeB6041 Hepatitis C virus envelope protein E2 enhances
human lipoprotein binding to cells
S. W0nschmann, J.T Stapleton. Iowa City VAMC and University of Iowa, Internal
Medicine SW34-P, GH, University of Iowa, 200 Hawkins Drive, UIHC, Iowa City
United States
Background: Hepatitis C virus (HCV) in serum has been shown to be associated with lipoproteins, and the low-density lipoprotein receptor (LDLr) has been
proposed as a cell receptor for HCV. Two clinical studies found lower rates of
cholesterol in HIV-HCV co-infected individuals. We studied the molecular basis of
HCV-lipoprotein (LP) interactions, and the role of E2 - LP interactions on HCV cell
attachment.
Methods: Recombinant HCV E2 was added to MOLT-4 cells in the presence or
absence of lipoproteins at 4~C, and specific cell binding of HCV E2 and lipoproteins was detected by FACS either with HCV E2-specifc antibody or directly labeled lipoproteins. HCV E2 complexed with lipoprotein was also evaluated by
ELISA.
Results: Incubation of HCV E2 protein with fluorescent-labeled low-density
lipoprotein (LDL) resulted in an increase in LDL binding to MOLT-4 cells by FACS.
Human VLDL, LDL, and HDL all enhanced HCV E2 protein binding to MOLT-4
cells, whereas rabbit LPs did not. Human LPs specifically interacted with HCV
envelope glycoproteins, since binding of fluorescent-labeled HIV gpl20 was not
altered by the addition of LPs. Human LDL enhanced HCV E2 binding, whereas
the lipid-free apoprotein component of LDL (apoB) did not. Using an
ELISA, HCV E2 -LP complex was captured by an anti-LDL antibody and detected
with an HCV E2 specific McAb.
Conclusions: HCV E2 interacted with human lipoproteins and enhanced LP
binding to cells. In addition, human LPs enhanced HCV E2 protein binding to cells
through an interaction involving the lipid-moiety of the LPs and subsequent use of
the LDL receptor and CD81. Our data suggest that native HCV particles bind to
serum lipoproteins via the viral envelope protein E2. This may result in enhanced
uptake of LDL, and thus may provide a molecular basis for the observation of
lower circulating LDL cholesterol levels in HIV-HCV co-infected individuals.
Presenting author: Jack Stapleton, Internal Medicine SW34-P, GH, University of
Iowa, 200 Hawkins Drive, UIHC, Iowa City, United States, Tel.: [phone],
Fax: [phone], E-mail: jack-stapleton @ uiowa.edu
WePeB6042I Feasibility of interferon-alpha 2b and ribavirin
combination therapy for chronic hepatitis C in HIV
and HCV coinfected patients in a real life clinical
setting
B. Jarrousse1, M. Bentata1, P. Honore, R. Mansouri1, E. Gordien2, C. AIoui2,
0. Launay3, 0. Lortholary3. IMddecine Interne - H6pitalAvicenne -Universite
Paris-Nord, Medecine Interne H6pital Avicenne, 125 rue de Stalingrad, 93009
Bobigny Cedex, France; 2Virologie - H6pital Avicenne -Universitd Paris-Nord,
Bobigny, France; 3Maladies Infectieuses - H6pital Avicenne -Universit6
Paris-Nord, Bobigny France
Background: Our objective was to determine the feasibility of interferon-alpha 2b
(IFN) plus ribavirin (RBV) therapy for chronic hepatitis C (CHC) in HIV and HCV
coinfected patients(pts).
Methods: Coinfected pts were screened since january 1998 for age, gender, CD4
count, HIV viral load (VL), antiretroviral therapy (ART), duration of HCV infection,
HCV-RNA, alcohol intake, liver biopsies results and CHC treatment. Differences
between treated and untreated pts were identified by chi-square test, Fisher's exact test, or Student's T test when appropriate. Significant factors were analyzed
by logistic regression.
Results: 226 pts were included: 177(78.3%) under ART, 194(85.8%) with HCVRNA replication, 68(30%) reporting alcohol consumption. Median duration of HCV
infection was 228 months. Metavir activity and fibrosis scores were 1.46 ~ 0.8 and
1.75 ~ 1.2 respectively in 104 pts (13.8% with cirrhosis). 62 of 226 pts(27.5%)
were eligible for CHC treatment and 42 pts(18.6%) were treated mainly with IFN
plus RBV(81%). 24 of 42 pts completed a one year treatment, 14 pts achieved
clearance of HCV-RNA. In contrast, 164(72.5%) pts were not eligible because of
AIDS or low CD4 count (22.6%), poor compliance (42%), lack of HCV replication
or significant fibrosis (32.4%), and severity of cirrhosis (3%). No difference between treated and untreated pts was observed for age, gender, mean CD4 count,
ART, alcohol and fibrosis score. The percentages of pts with undetectable VL
and HCV replication were higher in CHC treated pts (61.9% versus 38.04%,
p=0.005;100% versus 83.1%, p=0.0002). High CD4 count and undetectable VL
were strongly associated with the decision of CHC treatment by logistic regression (OR= 2.76, 95%C1: 1.00-7.61, p=0.04; OR= 0.391, 95%CI:0.18-0.82,p=0.01
respectively).
Conclusion: Our data reveal a poor feasibility of IFN plus RBV therapy for CHC
in patients with HIV-HCV coinfection in a real life setting.
Presenting author: bernard jarrousse, Medecine Interne H6pital Avicenne, 125
rue de Stalingrad, 93009 Bobigny Cedex, France, Tel.: [phone], Fax: +33

1 48955887, E-mail: [email protected]