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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
Management of Treatment-Experienced Patients
The Body PRO Coverage of the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008)
February 3-6, 2008Boston, Mass.
Faculty:Kathryn Anastos, M.D.Cal Cohen, M.D., M.S.David Wohl, M.D.
Cal Cohen, M.D., M.S.
CROI 2008:Coverage From
The Body PRO
Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
Kathryn Anastos, M.D.Kathryn Anastos, M.D., is the Executive Co-Director for Clinical and Scientific Programs of WE-ACTx (Women's Equity in Access to Care and Treatment, a community-based organization committed to providing HIV primary care, including antiretroviral therapy, to female survivors of genocidal rape in Rwanda. She has also developed and serves as the Principal Investigator of the Rwandan Women's Cohort Study (RWISA), funded by the U.S. National Institutes of Health (NIH). She is currently Professor of Medicine, Epidemiology and Population Health at Albert Einstein College of Medicine, Bronx, N.Y. Additionally, since 1993, Dr. Anastos has served as the Principal Investigator for the New York City/Bronx Consortium of the Women's Interagency HIV Study (WIHS), also funded by NIH.
Cal Cohen, M.D., M.S.Dr. Cal Cohen is the research director of Harvard Vanguard Medical Associates and Community Research Initiative of New England in Boston, Mass. He is also a clinical instructor at Harvard Medical School. In addition, he works as an HIV clinical management consultant and internist at Harvard Pilgrim Health Care. Dr. Cohen holds appointments at Brigham and Women's Hospital and Beth Israel Hospital, both in Boston, Mass. In addition to caring for HIV-infected patients and directing clinical research at a large HIV community-based research site, Dr. Cohen is actively involved in evaluating new antiretroviral therapies, the durability and longevity of the benefits from such therapies and issues regarding compliance and adherence. Dr. Cohen has served as a consultant to or has received honoraria or research support from Abbott Laboratories, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline and Tibotec.
David Wohl, M.D. Dr. Wohl is an associate professor of medicine at the University of North Carolina at Chapel Hill, and co-directs HIV services for the North Carolina Department of Corrections. Dr. Wohl is an investigator in the NIAID-sponsored AIDS Clinical Trials Group (ACTG) and a member of the ACTG Complications of HIV Disease Research Agenda Committee. His research focuses on metabolic and infectious complications of HIV and its therapies, as well as issues related to medication adherence and access to care—particularly among incarcerated inmates with HIV infection. Dr. Wohl has served as a consultant to or has received honoraria or research support from Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck & Co, Roche Laboratories and Tibotec.
This activity is supported by an educational grant from
Faculty
CROI 2008:Coverage From
The Body PRO
Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
About This Slide Presentation
• This presentation was created to accompany The Body PRO's summary of key research presented at CROI 2008, featuring reports by Kathryn Anastos, M.D., Cal Cohen, M.D., M.S., and David Wohl, M.D. For more information about this program, please visit us on the Web at: TheBodyPRO.com/CROI2008
• Please feel free to use this slide presentation for personal reference or for your own presentations; however, we ask that you not modify any aspects of the slides contained within this presentation, so proper attribution can be retained. If you would like to publish all or part of this presentation, or repost any of these slides online, permission must first be obtained from Body Health Resources Corporation.
• Our gratitude goes out to all the researchers who granted permission for their slides to be adapted for this presentation.
CROI 2008:Coverage From
The Body PRO
Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
HIV Resistance Incidence on a Province-Wide Basis
0
100
200
300
400
500
600
1996
1998
2000
2002
2004
2006
2008
3TC
NRTI
NNRTI
PI
Any
Number of New Cases
of Resistance Detected
Viviane Lima et al. CROI 2008; abstract 895. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
VICTOR-E1: Mean Change in HIV-1 RNA From Baseline at Week 48 All ITT Subjects
*Comparing VCV to Control based on ANOVAMissing values of change from baseline imputed by the average of immediately preceeding and following non-missing values; in other cases, missing values imputed by zero.
-1.77 -1.75
-0.79
-2
-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
Me
an
Ch
an
ge
in
HIV
-1 R
NA
Fro
m
Ba
se
lin
e (
log
10
co
pie
s/m
L)
VCV 20 mg + OBTn = 40
VCV 30 mg + OBTn = 39
Placebo + OBTn = 35
Difference: -0.98P = 0.0017*
Difference: -0.98P = 0.0026*
Primary Study Endpoint Overall Population
-1.75
-1.47
-1.14
-2
-1.8
-1.6
-1.4
-1.2
-1
-0.8
-0.6
-0.4
-0.2
0
VCV 20 mg + OBTn = 12
VCV 30 mg + OBTn = 12
Placebo + OBTn = 10
Difference: -0.61
Difference: -0.33 M
ea
n C
ha
ng
e i
n H
IV-1
RN
A F
rom
B
as
eli
ne
(lo
g 1
0 c
op
ies
/mL
)
Subjects Baseline HIV-1 RNA > 100,000
copies/mL
Barry Zingman et al. CROI 2008; abstract 39LB. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
VICTOR-E1: Percentage of Subjects With HIV-1 RNA < 400 Copies/mL at Week 48
24 9 7 6 6 6 13 11 16 13 11
Overall By No. Active Drugs in OBT*
n = 26
% o
f Sub
ject
s
67%71%
83%
69%
57%60%
83%
85%
46%
25%26%
33%
45%
18%
0%0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%VCV 30 mg + OBT
VCV 20 mg + OBT
Placebo + OBT
7 8 7
≥3 2 1 0
P = 0.0004 30 mg
* OSS: Defined as fully sensitive
treatment in OBT by Monogram PhenoSense.
Partially sensitive patients
were designated as resistant.
Barry Zingman et al. CROI 2008; abstract 39LB. Reprinted with permission.
CROI 2008:Coverage From
The Body PRO
Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
VICTOR-E1: Adverse Event Rate by Time on Study
*Rate > 10/100 person-years.
All Casualties and SeveritiesAll Patients Receiving One Dose
VCV 30 mg + OBTRate
VCV 20 mg + OBTRate
Placebo + OBT Rate
Total Exposure in Person-Years (P-Y)* 33.2 34.67 22.39
SAE’s n (P-Y) 4 (12) 5 (14.4) 5 (22.3)
Any Adverse Event 111.4 112.5 147.4Diarrhea 45.2 31.7 40.2Respiratory Symptoms 24.1 51.9 22.3
Nausea 15.1 8.7 22.3Pyrexia 15.1 11.5 17.9Dizziness 15.1 2.9 17.9Headache 15.1 8.7 31.2Tinea Pedis 12.1 0 4.5Lymphadenopathy 9.0 20.2 8.9Depression 9.0 11.5 26.8Musculoskeletal Pain 9.0 8.7 40.2Asthenia 6.0 2.9 13.4Fatigue 6.0 14.4 13.4Upper Abdominal Pain 3.0 14.4 0Flatulence 3.0 5.8 17.9Anorexia 0 0 13.4
Barry Zingman et al. CROI 2008; abstract 39LB. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
MOTIVATE: Percentage of Patients With HIV-1 RNA < 50 Copies/mL at Week 48 by Screening HIV-1 RNA* and by Baseline† CD4+ Cell Count
David Hardy et al. CROI 2008; abstract 792. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
MOTIVATE: Percentage of Adverse Events Occurring in ≥ 5% of Patients in Any Group (Unadjusted for Study Treatment Exposure)
David Hardy et al. CROI 2008; abstract 792. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
Screen and Baseline Tropism Reclassifications Amongst Subjects With R5 Virus Only by Standard Trofile
Jacqueline Reeves et al. CROI 2008; abstract 869. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
BENCHMRK-1 & 2: Combined EfficacyPercent of Patients With HIV RNA < 50 Copies/mL at Week 48 by Genotypic Sensitivity Score (GSS)
For patients with GSS = 1, 4 ART agents represented at least 80% of the active agents in OBT: darunavir (52%, 52% in raltegravir and placebo groups, respectively), enfuvirtide (8%, 16%), tenofovir (12%, 6%), and tipranavir (11%, 11%).
David Cooper et al. CROI 2008; abstract 788. Reprinted with permission. Copyright © 2008 Merck & Co., Inc., Whitehouse Stations, New Jersey, USA, All Rights Reserved
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
BENCHMRK-1 & 2: Combined EfficacyPercent of Patients HIV RNA < 50 Copies/mL At Week 48 by PSS Based on Upper and Lower Cutoffs
The analysis by PSS score has been reanalyzed using the upper cutoff to better account for the impact of partial ART activity.Isolates with fold-change IC50 above the lower but below the upper cutoff are now reported as "partially sensitive." The upper cutoff was developed as the lower
cutoff may underestimate partial ART activity in a regimen. At the time the BENCHMRK studies were initiated, only the lower cutoff was reported. The efficacy by PSS has been reanalyzed using the upper cutoffs, where
available, to better account for the impact of partial ART activity.Conclusion: At all levels of PSS, the results using the upper and lower cutoffs are similar, confirming the contribution of raltegravir in the treatment regimen.
David Cooper et al. CROI 2008; abstract 788. Reprinted with permission. Copyright © 2008 Merck & Co., Inc., Whitehouse Stations, New Jersey, USA, All Rights Reserved
1
BENCHMRK-1 & 2 Combined Efficacy Percent of Patients With HIV RNA <50 copies/mL
at Week 48 by PSS Based on Upper and Lower cutoffs
Percent of PatientsNPSS
PSS = 0 (Based on lower cutoff )
PSS = 1 (Based on lower cutoff)
Raltegravir + OBT Placebo + OBT
0 20 40 60 80 100
51
52
61
48
71
70
2
8
29
13
48
43
m518p18p19bar50PSScutoffs012wk48
65
33
137
71
221
313
44
12
69
54
108
153
Raltegravir + OBT Placebo + OBT
PSS = 0 (Based on upper cutoff)
PSS = 1 (Based on upper cutoff)
PSS >= 2 (Based on lower cutoff)
PSS >= 2 (Based on upper cutoff)
Virological failures carried forward
n
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
BENCHMRK-1: Summary of Clinical Adverse Events (AEs)
Raltegravir + OBT Placebo + OBT
(n = 232) (n = 118) Difference From Placebo†
% % % (95% CI) P-Value
Mean Follow-Up (Weeks)
% Patients With: Any AE
54.5
90.9
38.6
84.7
6.20 (-0.7, 14.4)
0.105
Drug-related‡ AE
48.7 54.2 -5.53 (-16.4, 5.6)
0.366
Serious AE
19.8 17.8 2.03 (-7.1, 10.2)
0.774
Serious Drug-Related AE 3.0 0.8 2.17 (-1.8, 5.4)
0.275
Deaths
1.3 2.5 -1.25 (-6.0, 1.7)
0.409
Discontinued Due to AE
1.7 3.4 -1.67 (-6.8, 1.6)
nps§
†Tests of significance were performed on the percentage of patients with at least one adverse event in the category. The 95% CIs were calculated using Miettinen and Nurminen's method. P-Values were generated using the Fisher exact test.
‡Determined by the investigator to be possibly, probably, or definitely drug related.
§nps=not pre-specified for statistical analysis.
David Cooper et al. CROI 2008; abstract 788. Reprinted with permission. Copyright © 2008 Merck & Co., Inc., Whitehouse Stations, New Jersey, USA, All Rights Reserved
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
DUET-1: Response (< 50 Copies/mL) By PSS (DRV FC < 10)* at Week 48
Richard Haubrich et al. CROI 2008; abstract 790. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
DUET-1: Response (< 50 Copies/mL) By PSS (DRV FC < 40)* at Week 48
Richard Haubrich et al. CROI 2008; abstract 790. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
TITAN: Number of VFs and Resistance Development in VFs
Sandra De Meyer et al. CROI 2008; abstract 874. Reprinted with permission.
CROI 2008:Coverage From
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Management of Treatment-Experienced Patients: A Summary of Key CROI 2008 Research
TITAN: Proportion of Isolates Remaining Susceptible to PIs Upon VF (Phenotypic Antivirogram Data)
Sandra De Meyer et al. CROI 2008; abstract 874. Reprinted with permission.