Transcript Slide 1

THE BODY PRO
The HIV Resource for Health Professionals
New Developments in HIV/Hepatitis C
Coinfection Management and
Epidemiology: Highlights From
ICAAC/IDSA 2008
Faculty: Daniel Fierer, M.D.
Assistant Professor of Medicine at the Mount Sinai
School of Medicine
The Body PRO Covers ICAAC/IDSA 2008
Washington, D.C.; October 25-28, 2008
This activity is jointly sponsored by Postgraduate
Institute for Medicine and The Body PRO.
Copyright © 2009 The HealthCentral Network, Inc. All rights reserved.
Daniel Fierer, M.D.
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Faculty for This Activity
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Daniel Fierer, M.D.
Daniel Fierer, M.D., is an assistant professor of medicine and infectious diseases
at the Mount Sinai School of Medicine in New York City.
Dr. Fierer earned his medical doctorate from the Yale University School of
Medicine in 1986. He trained in internal medicine at the University of California,
San Diego, and completed postgraduate fellowships in infectious diseases at the
National Institutes of Health and the University of California Hospitals.
Dr. Fierer's research interests focus primarily on HIV/hepatitis C (HCV)
coinfection, and he is the co-author of numerous journal articles and studies in
this area. He initiated a study evaluating HIV-infected patients referred by their
physicians for acute HCV infection. The aim of the study was to further investigate
the early effects of HCV infection on liver pathology, the natural history of the
disease, the effectiveness of treatment and the mode of transmission.
Disclosures
Dr. Fierer has no real or apparent financial relationship to disclose related to the
topic of this activity.
This activity is supported by an educational grant from
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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HCV in the HIV-Infected Patient:
Case Study, 56-Year-Old Caucasian
Male With HIV and Hepatitis C
 Exposure to HIV and HCV: Late 1970s
 Diagnosis: Early 1990s
 No ART
 CD4+ lymphocyte 782/mm3
 HIV RNA < 400 copies/ml
 HCV genotype 1a; HCV RNA 6.4 log IU/ml
 ALT 77; INR 1, TB 1.9; creat 1; plts 219K
 Liver biopsy 2001: mild fat; no fibrosis
Adapted from David Thomas. ICAAC/IDSA 2008; abstract 849.
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HCV in the HIV-Infected Patient:
ACTG 5178 No Benefit of Maintenance
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 No benefit of 18 months
of maintenance
N = 21
 DSMB stopped study
 Cirrhosis 18% and 21%
of maintenance and
observation arms
N = 24
Change in Metavir Fibrosis
Sherman and ACTG 5178 team, CROI 2008
Adapted from David Thomas. ICAAC/IDSA 2008; abstract 849.
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Ritonavir-Boosted PI and Not Abacavir
Adversely Impacts HCV Treatment: Treatment
Response by Regimen Type (n = 27)
P Value
(chi-square)
Non-Ritonavir
Containing
Regimens
Ritonavir
Containing
Regimens
EVR
0.03
12/18 (67%)
2/9 (22%)
SVR
0.03
7/18 (39%)
0/9 (0%)
Non-Abacavir
Abacavir
EVR
0.34
5/12 (42%)
9/15 (60%)
SVR
0.33
2/12 (17%)
5/15 (33%)
Non-PI
Any PI
EVR
0.18
10/16 (63%)
4/11 (36%)
SVR
0.06
6/16 (38%)
1/11 (9%)
EVR = early virologic response; SVR = sustained virologic response
Adapted from Rohit Talwani et al. ICAAC/IDSA 2008; abstract V-1632.
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Infectious Complications During Peg-IFN
Plus Ribavirin in HIV-Infected Patients With
Chronic Hepatitis C: Patients and Methods
• Prospective cohort of 174 consecutive
HIV/HCV-coinfected patients who started
their first course of treatment with peg-IFN
α-2a (53%) or peg-IFN α-2b(47%) plus
weight-adjusted ribavirin, between
January 2001 and March 2006.
• Monthly visits during the treatment
period were performed. All adverse
effects, including infectious complications,
were systematically recorded.
• The frequency of infectious
complications was compared between
patients with or without neutropenia WHO
grade 3 or 4 (< 750/mm3) and with or
without CD4+ cells below 200/mm3 by
means of Chi square test.
Ana Moreno et al. ICAAC/IDSA 2008; abstract V-1633. Reprinted with permission.
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Infectious Complications During Peg-IFN
Plus Ribavirin in HIV-Infected Patients With
Chronic Hepatitis C: Results
• During the study period almost half the
population developed an infectious
complication during therapy (117 infections in
84 patients, 48%).
• The median time to an infectious event was
12 weeks (IQR 8; 24).
• Grade 3-4 neutropenia was observed in 51
subjects (29%), but only in 2% led to peg-IFN
dose reduction. There were no treatment
withdrawals. 30 of 51 patients received G-CSF
(59%), with favorable response.
• The most frequent infectious complications
were respiratory tract infections (31% of
patients).
• Patients with WHO grade 3 or 4 neutropenia,
or with CD4+ counts below 200 cells/ml during
therapy, did not have more frequency of
infectious events.
Ana Moreno et al. ICAAC/IDSA 2008; abstract V-1633. Reprinted with permission.
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HAART Is Associated With a Lower Level of
Hepatic Necroinflammatory Activity:
Characteristics of Study Population
Jose F. Pascual Pareja et al. ICAAC/IDSA 2008; abstract H-2319. Reprinted with permission.
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HAART Is Associated With a Lower Level of
Hepatic Necroinflammatory Activity: Factors
Associated With Necroinflammatory Activity ≥ 3
Jose F. Pascual Pareja et al. ICAAC/IDSA 2008; abstract H-2319. Reprinted with permission.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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HCV Treatment Eligibility in ERCHIVES:
Characteristics of HCV and HCV/HIV-Coinfected
Subjects With and Without HCV RNA Availability
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract V-1634. Reprinted with permission.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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HCV Treatment Eligibility in ERCHIVES:
Flowchart of Treatment Eligibility and
Contraindications in the HCV/HIVCoinfected Subjects
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract V-1634. Reprinted with permission.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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Low HCV Treatment Rates After a
Liver Biopsy: Liver Biopsy Findings
Batts-Ludwig Scale F0-F4 (n = 163)
All HCV+ pts
(n = 163)
HIV+/HCV+
(n = 83)
HIV-/HCV+
(n = 80)
20
53
24
3
19
55
24
1
21
51
24
4
42
31
16
11
58%
38
34
16
12
62%
45
29
16
9
55%
Inflammation (%)
Grade 1
Grade 2
Grade 3
Grade 4
Fibrosis (%)
F 0-1
F2
F3
F 4 (Cirrhosis)
[Fibrosis > F2]
There were no significant differences in liver histology between HIV-positive and HIV-negative patients
Oluwatoyin M. Adeyemi et al. ICAAC/IDSA 2008; abstract V-1637. Reprinted with permission.
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Low HCV Treatment Rates After a
Liver Biopsy: Predictors of HCV
Treatment Post-Liver Biopsy
 61 patients (37%) received HCV treatment post-liver biopsy
 31 (37%) of HIV-positive patients and 30 (38%) of HIV-negative
patients received HCV treatment
 49% of all patients with significant fibrosis (≥ F2) received HCV
treatment
 Women were more likely to receive treatment: 50% vs. 32%
(P = .05)
 African Americans less likely to receive treatment: 27% vs. 50%
(P = .01)
 Patients with more advanced histology were more likely to receive
HCV treatment
 Fibrosis ≥ F2: 49% vs. 22% (P = .001)
 Fibrosis F4 (cirrhosis): 70% vs. 34% (P = .001)
Oluwatoyin M. Adeyemi et al. ICAAC/IDSA 2008; abstract V-1637. Reprinted with permission.
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Low HCV Treatment Rates After a
Liver Biopsy: Reasons for
Non-Treatment Post-Liver Biopsy
n = 102: 52 HIV+, 50 HIV-
Oluwatoyin M. Adeyemi et al. ICAAC/IDSA 2008; abstract V-1637. Reprinted with permission.
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PERICO: Main Results at Week 4 of
Hepatitis C Therapy According to
Treatment Arm
RBV 1.0 – 1.2 g/day
(N = 75)
RBV 2.0 g/day
(N = 74)
P
12.7 [11.1 to 14.2]
13.4 [11.1 to 15.6]
0.04
Mean Δ Hb [Baseline to Week 4]
(g/dL)
-2.4 [1.5 to 3.2]
-1.8 [0.3 to 3.7]
0.06
Mean Δ HCV-RNA [Baseline to Week
4] (log IU/mL)
-2.4 [-1.2 to -4.1]
-2.6 [-1.6 to -3.6]
0.5
Mean RBV Plasma Concentration
(µg/mL)
1.9 [1.4 to 2.6]
2.4 [1.7 to 3]
0.2
Patients With Severe Anemia at Week
4 [Hb < 10 g/dL] (%)
4 (6.6%)
2 (3.3%)
0.4
16 (22%)
16 (22%)
1
1 (1.3)
2 (2.8)
0.6
Mean Hb at Week 4 (g/dL)
Patients With RVR (%)
Treatment Discontinuation or RBV
Dose Reduction Due to Anemia (%)
Adapted from Vicente Soriano et al. ICAAC/IDSA 2008; abstract H-2321.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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New HCV Drugs in the Pipeline:
Sustained Virological Response in
Subgroups of Interest
Race
Baseline Viral Load
METAVIR Fibrosis
Score
African
American
Caucasian
Low ≤
600,000 IU/mL
High >
600,000 IU/mL
0/1/2
3/4
PEG-IFN
-2b 1.0/RBV
N = 1016
17%
44%
59%
33%
39%
30%
PEG-IFN
-2b 1.5/RBV
N = 1019
23%
44%
61%
35%
42%
21%
PEG-IFN
-2a 180/RBV
N = 1035
26%
44%
66%
36%
44%
24%
Adapted from Mark Sulkowski. ICAAC/IDSA 2008; abstract 850.
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Does the Choice of peg-IFN Formulation Affect
Safety or Efficacy in HIV/HCV-Coinfected Patients
Receiving Weight-Adjusted Ribavirin?: Overall
Outcomes According to peg-IFN Formulation
Peg-IFN! -2a (n=93)
Peg-IFN! -2b (n=81)
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P
HCV-RNA (log10IU/ml; mean±SD)
Week 4
2,96 ± 2,42
2,83 ± 2,51
0.72
Week 12
1,80 ± 2,28
2,40 ± 2,6
0.21
Week 24
1,31 ± 2,20
1,84 ± 2,6
0.27
Week 4
33
41
0.28
Week 12
54
48
0.44
Week 24
68
62
0.46
EVR (%)
70
57
0.07
SVR (%)
49,5
41
0.24
Early withdrawals (%)
15
18
0.54
Negative HCV-RNA (%)
Ana Moreno et al. ICAAC/IDSA 2008; abstract V-1631. Reprinted with permission.
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New HCV Drugs in the Pipeline:
Multiple Direct Antiviral Agents Have
Entered Clinical Development
Polymerase
Protease
Other
GS 9190
BILN 2061*
A-831
HCV-796*
Boceprevir (phase 3)
BMS
R1626 (phase 2)*
ITMN-191 (phase 1)
GS 9132*
R7128 (phase 2)
MK7009 (phase 1)
Valopicitabine*
Telaprevir (phase 3)
VCH-759
TMC435350 (phase 2)
*Development is on hold.
Adapted from Mark Sulkowski. ICAAC/IDSA 2008; abstract 850.
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SMART*: Primary and Major
Secondary End Points
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Adapted from Wafaa El-Sadr et al. N Engl J Med. 2006;355(22):2283-2296.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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Hepatitis C Virus Infection and the
Risk of Coronary Disease: Results
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A flow chart depicting the number of subjects included in the study.
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract V-4219. Reprinted with permission.
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Hepatitis C Virus Infection and the Risk of
Coronary Disease: Results: Factors
Associated With CAD (Multivariable Cox)
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract V-4219. Reprinted with permission.
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HIV Infection and the Risk of Diabetes Mellitus:
Baseline Characteristics of HIV-Infected and
Uninfected Persons in the Veterans Aging
Cohort Study
Age at study entry,
mean (SD) years
HIV +
(n=3,227)
HIV –
(n=3,240)
Pvalue
49.6 (8.8)
50.8
(10.0)
<0.001
HIV +
(n=3,227)
HIV –
(n=3,240)
White
19.9
24.3
Black
66.7
62.1
4.6
5.1
35-39
7.4
6.7
Hispanic
9.5
10.0
Other/Unknown
3.9
3.6
40-44
14.9
12.9
45-49
23.5
21.6
Hepatitis C infection
(%)
31.2
15.4
<0.001
50-54
22.3
22.1
55-59
16.4
16.3
60-64
5.4
6.0
65-69
2.9
4.3
≥70
2.5
5.0
97.5
92.1
Gender (% male)
<0.001
Diabetes (%)
14.9
21.4
<0.001
Height (SD) (meters)
1.77
(0.07)
1.77
(0.08)
0.6
Weight (SD)
(kilograms)
79.1
(15.4)
90.6
(19.4)
<0.001
Body mass index,
mean (SD)
<0.001
25.2 (4.5)
28.9 (5.6)
<0.001
Pvalue
Race
Age at study entry (years)
<35
21
<0.001
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract H-2306. Reprinted with permission.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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HIV Infection and the Risk of Diabetes Mellitus:
Baseline Characteristics of HIV-Infected and
Uninfected Persons in the Veterans Aging
Cohort Study (Continued)
HIV +
(n=3,227)
HIV –
(n=3,240)
Pvalue
Body mass index
Drug use (%)
<20
9.2
3.2
20-24.9
41.2
20.2
25-29.9
37.3
39.2
≥30
12.3
37.4
23.7
20.9
1-4
25.3
25.1
5-10
13.3
12.7
11-30
17.1
17.2
31-60
7.1
8.0
13.5
16.2
>60
HIV +
(n=3,227)
HIV –
(n=3,240)
Pvalue
50.7
38.3
<0.001
HIV+
<0.001
CD4+ lymphocyte count/mm3, N (%)
≤200
695 (23.9)
*
1,331
(45.7)
*
886 (30.4)
*
Median (SD) CD4+
lymphocyte count
366 (264)
*
Median HIV RNA
(SD), Log10
copies/ml
3.08
(1.87)
*
201-500
Alcohol use (average number of drinks
per month)
0
22
>500
0.01
* Not included in the model, since HIV-uninfected subjects were included
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract H-2306. Reprinted with permission.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008
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HIV Infection and the Risk of Diabetes
Mellitus: Discussion
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• We found that HIV infection per se was not associated with a higher risk of diabetes mellitus (DM). In fact, the risk of DM at
baseline was lower in the HIV-infected (OR 0.84, 95% CI 0.72-0.97) compared with HIV-uninfected persons.
• There were many differences in the prevalence of risk factors for DM in the HIV-infected and uninfected persons. HIVinfected persons were younger and had a lower body mass index (BMI), which decreases the risk for DM, but were more
likely to be racial minorities and had a higher prevalence of HCV, which increases risk.
• We found that HCV infection is associated with a higher risk of DM in the HIV-infected group, and demonstrated a similar
trend in the uninfected group in multivariable analysis (although this trend did not reach statistical significance, the effect
size was similar).
• We found that use of combination antiretroviral therapy (CART) was associated with a significantly higher risk of DM in the
HIV-infected group.
• Our finding of a lower risk of DM associated with increasing alcohol use and drug use is intriguing. Increasing
quantity/frequency of alcohol use was associated with increasing protection except in HIV-infected persons who consumed
> 60 drinks per month. Increasing alcohol use is associated with increasing liver damage, and may be expected to increase
the risk of diabetes. We conducted separate analyses including liver damage (defined as alanine or aspartate
aminotransferase levels > 5 times upper limit of normal) with and without HCV in the models and found no significant
association with liver damage. It is also plausible that increased alcohol consumption and drug abuse or dependence may
lead to poor nutrition and lower BMI which may indirectly afford protection from DM. However, we found no significant
association between quantity and frequency of alcohol use and BMI. Another possibility is that people with alcohol and drug
abuse may not seek medical care and the opportunity to diagnose DM may have been missed. We did find that
non-drinkers were older, while moderate to heavy drinkers were more likely to be younger. These data suggest that while
some of the protective effect of alcohol is due to the alcohol consuming population being younger, there are other likely
mechanisms that modulate this effect.
Adeel A. Butt et al. ICAAC/IDSA 2008; abstract H-2306. Reprinted with permission.
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Sharp Decline in the Seroprevalence of
Hepatitis C Virus Among HIV-Infected
Patients in Spain: Baseline Characteristics
Baseline
Characteristics
CoRIS-MD (n=2,611)
(1997-2003)
CoRIS (n=2,559)
(2004-2006)
Total (n=5,170)
n
Freq.
n
Freq.
n
Freq.
721
27.61%
598
23.37%
1,319
25.51%
1,522
58.29%
532
20.79%
2,054
39.73%
Gender
Female
HCV status
Infected
Transmission pathway
MSM
378
14.48%
979
38.26%
1,357
26.25%
IVDU
1,394
53.39%
473
18.48%
1,867
36.11%
Heterosexual
624
23.90%
968
37.83%
1,592
30.79%
Other
215
8.23%
139
5.43%
354
6.85%
591
22.64%
608
23.76%
1,199
23.19%
1,580
60.51%
1,151
44.98%
2,731
52.82%
440
16.85%
800
31.26%
1,240
23.99%
Age (categorical)
Less than 30
30 to 39.9
40 or more
MSM: males who have sex with males; IVDU: intravenous drug user.
Santiago Moreno et al. ICAAC/IDSA 2008; abstract V-1629. Reprinted with permission.
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Acute Hepatitis C: Management and
New Epidemiology: Risk Factors for
Acute HCV: Case-Control Study
• Unprotected receptive anal intercourse with (P = .04) or without
(P = .03) ejaculation
• Unprotected receptive oral sex with ejaculation (P = .03)
• Use of sex toys (P = .03)
• “Sex while high” (P = .01)
• Use of marijuana (P = .04)
Daniel Fierer. ICAAC/IDSA 2008; abstract 851. Reprinted with permission.
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Acute Hepatitis C: Management and
New Epidemiology: Fibrosis During
Acute HCV Infection in HIV-Positive Men
20 patients underwent liver biopsy:
• Median 4 months after detection of ALT elevation (range 3 weeks
to 4 1/3 years)
• 17 (85%) had stage 2 of 4 fibrosis (Scheuer)
• 2 had stage 1
• 1 had stage 0
Daniel Fierer. ICAAC/IDSA 2008; abstract 851. Reprinted with permission.
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Acute Hepatitis C: Management and New
Epidemiology: Acute HCV Infection of HIV-Positive
Men Who Have Sex With Men (MSM): Conclusions
• Acute HCV infection of HIV-positive men is a newly described clinical
syndrome:
— Route of transmission related to sex
— Moderately advanced fibrosis occurs within weeks to months
and does not regress in years
• Emerging infection in the US as well as in Europe
• Enhanced surveillance in HIV-positive MSM should be performed to
enable detection and curative treatment in the acute phase to prevent
further progression of already significant liver fibrosis.
— LFTs every 3 months, Ab every 6-12 months
Daniel Fierer. ICAAC/IDSA 2008; abstract 851. Reprinted with permission.
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• This presentation was created to accompany The Body PRO's summaries
of key research presented at ICAAC/IDSA 2008, by Daniel Fierer, M.D.
• The Body PRO's extensive coverage of ICAAC/IDSA 2008 also includes:
– Summaries and analyses of research on a wide array of clinical
subjects.
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studies.
– Audio podcasts you can play online or download to your computer or
MP3 player.
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• Visit TheBodyPRO.com/ICAAC2008 today for a full listing of our
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Disclaimer:
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The information provided through The Body PRO should not be used for diagnosing or treating a health problem or a disease.
New Developments in HIV/Hepatitis C Coinfection Management and Epidemiology: Highlights From ICAAC/IDSA 2008