Transcript CROI 2010 www.hivandmore.de Design: Quad- und GS-9350 Phase-2-Studien Comparison EVG/GS-9350/TDF/FTC + placebo n = 48 Eligible Subjects 2:1 Treatment-naïve HIV RNA ≥5,000 copies/mL CD4 cells >50 cells/mm3 No Resistance to NRTIs NNRTIs PIs HBV-

CROI 2010
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Design: Quad- und GS-9350 Phase-2-Studien
Comparison
EVG/GS-9350/TDF/FTC + placebo
n = 48
Eligible Subjects
2:1
Treatment-naïve
HIV RNA ≥5,000 copies/mL
CD4 cells >50 cells/mm3
No Resistance to
NRTIs
NNRTIs
PIs
HBV- and HCV-negative
2:1
EVG/GS-9350
vs.
EFV/FTC/TDF + placebo
n = 23
Efavirenz
GS-9350 + placebo
ATV + FTC/TDF
n = 50
GS-9350
vs.
RTV + placebo
ATV + FTC/TDF
n = 29
RTV
• Randomization was stratified by HIV RNA (≤ or > 100,000 copies/mL)
• Primary Endpoint: Proportions with HIV RNA < 50 copies/mL at Week
24
Cohen C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 58LB.
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• 48-week trials
Baseline Characteristics
Quad
n=48
EFV/FTC/TDF
n=23
GS-9350
n=50
RTV
n=29
36
35
37
34
Male
92%
91%
94%
86%
Race
White
Black
69%
25%
78%
22%
62%
36%
55%
28%
HIV RNA
Mean, log10 copies/mL
>100,000 copies/mL
4.59
23%
4.58
22%
4.56
24%
4.69
38%
CD4 cells/mm3, median
354
436
341
367
AIDS
6%
4%
16%
10%
Age, mean years
Cohen C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 58LB.
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Primary Endpoint:
Percentage with HIV RNA < 50 copies/mL (ITT M=F)
RTV vs. GS-9350
EVG/GS-9350/TDF/FTC vs. EFV/FTC/TDF
Week 24 stratum-weighted difference
+5% (95% CI: -11.0% to 21.1%)
Week
Cohen C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 58LB.
86%
84%
% with HIV RNA <50 copies/mL
% with HIV RNA <50 copies/mL
90%
83%
Week 24 stratum-weighted difference
-1.9% (95% CI: -18.4% to 14.7%)
Week
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Adverse Events >5% Related to
Randomized Drug in Any Treatment Group
Quad
n=48
EFV/FTC/TDF
n=23
GS-9350
n=50
RTV
n=29
5 (10%)
8 (35%)
0
0
0
3 (13%)
0
0
Fatigue
4 (8%)
3 (13%)
1 (2%)
2 (7%)
Somnolence
2 (4%)
2 (9%)
0
0
Headache
2 (4%)
2 (9%)
1 (2%)
0
Diarrhea
4 (8%)
1 (4%)
3 (6%)
3 (10%)
Nausea
2 (4%)
1 (4%)
5 (10%)
1 (3%)
Abnormal Dreams,
Nightmares
Dizziness
Cohen C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 58LB.
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QUAD or GS-9350 Studies: Estimated GFR
(Cockcroft-Gault)
EFV/FTC/TDF
GS-9350
RTV
ELV/GS-9350
/TDF/FTC n=48
n=23
n=50
n=29
1
0
6
0
∆ Mean Serum Creatinine
Baseline to Week 24
+0.14 mg/dL
+0.04 mg/dL
+0.18 mg/dL
+0.14 mg/dL
∆ Mean eGFR*
Baseline to Week 24
-18 mL/min
-7 mL/min
-15 mL/min
-14 mL/min
Mean eGFR*
At Week 24
111 mL/min
126 mL/min
102 mL/min
111 mL/min
Incr Creatinine
(all Grade 1)
•
•
No treatment discontinuations due to renal adverse events
Separate study in normal volunteers receiving GS-9350 or placebo for 7 days
– Creat increase occurs in days, rapidly reversible, due to inhibition of tubular secretion
by drug
– No effect on GFR as measured by iohexol clearance
*Estimated GFR by Cockcroft-Gault
– Effect similar to that seen with cimetidine or trimethoprim
Cohen C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 58LB.
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Design Victor E3 und 4
• 2 randomized, identical, placebo-controlled, double-blind, phase 3
trials
TreatmentExperienced
R5-HIV only by
Trofile
ES
(N=721)
VCV 30 mg + OBT
Placebo + OBT
Week 24
Interim
analysis
Week 48
Final analysis
• Subjects ART-experienced with either documented resistance to ≥ 2
available drug classes (NRTI, NNRTI, or PI) or ART experience of at
least 6 months
• Primary endpoint: % HIV RNA < 50 copies/mL at 48 weeks
Gathe J, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 54LB
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Victor E3 und 4: Baseline Charakteristika
VICTOR-E3
VICTOR-E4
VCV
Control
VCV
Control
252
123
234
112
43 (0.6)
44 (0.9)
43 (0.6)
44 (0.8)
White, n ( % )
163 (65%)
85 (69%)
121 (52%)
67 (60%)
Female, n ( % )
85 (34%)
37 (30%)
66 (28%)
22 (20%)
Mean Base line HIV RNA log10 ( SE )
4.5 (0.1)
4.8 (0.1)
4.5 (0.1)
4.5 (0.1)
Mean CD4 Count, cells /mm3 (SE)
246 (11.9)
221 (17.1)
273 (11.3)
287 (18.0)
OSS = 2, n (%)
106 (42%)
54 (44%)
70 (30%)
31 (28%)
OSS = 3, n (%)
141 (56%)
67 (54%)
152 (65%)
78 (70%)
Raltegravir in OBT regimen , n (%)
95 (38%)
47 (38%)
59 (25%)
31 (28%)
Darunavir in OBT regimen , n (%)
94 (37%)
51 (41%)
90 (38%)
46 (41%)
N
Age, years ( SE )
Gathe J, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 54LB
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Victor E3 und 4: Wirksamkeit
(gepoolte Daten, MITT)
VCV
(N=486)
Control
(N=235)
HIV RNA < 50 at week 48
64%
62%
HIV RNA <400 at week 48
72%
71%
Mean Increase in CD4 (cells/ mm3)
138
129
n=176
N=85
Gathe J, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 54LB
n=293
n=145
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ACTG 5202 – Studiendesign
TDF/FTC QD
ABC/3TC Placebo QD
ABC/3TC QD
ART-naïve
(n=1857)
TDF/FTC Placebo QD
TDF/FTC QD
• 96 Wochen nach Einschluss letzter Patient
• 2005-2007, kein HLA B* 5701-Test
ABC/3TC Placebo QD
EFV
QD
EFV
QD
ATV/r
QD
•83% Männer, 40% Weiße
•VL 4.7 log, CD4 230/µl, 40% Resistenztest
•Vorhersage 32% VF zu Woche 96
# 59LB Darr E et al
ABC/3TC QD
TDF/FTC Placebo QD
ATV/r
QD
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A5202: Baseline Charakteristika
EFV
(n=465)
ATV/r
(n=463)
EFV
(n=464)
ABC/3TC
ATV/r
(n=465)
All Subjects
(N=1857)
TDF/FTC
Median Age (years)
37
38
39
39
38
Male (%)
79
84
85
83
83
White non-Hispanic
38
41
43
40
40
Black non-Hispanic
35
33
33
32
33
Hispanic
23
23
22
24
23
Median HIV RNA
(log10 c/mL)
4.7
4.6
4.7
4.7
4.7
Median CD4 (cells/mm3)
225
236
234
224
230
History of AIDS (%)
19
15
15
15
17
Genotype at screening (%)*
43
47
47
40
45
HCV positive (%)
6
9
9
7
7
Race/Ethnicity (%)
* Required for those with recent infection, otherwise optional
Daar E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 59LB.
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A5202: Zeit bis zum virologischen Versagen bei
HIV-RNA >100.000 K/ml
Wahrscheinlichkeit kein virologisches Versagen
TDF-FTC (26 events)
ABC-3TC (57 events)
P<0.001, log-rank test
Hazard ratio, 2.33 (95% CI, 1.46-3.72)
Kein Unterschied ATV/r und EFV
ABC-3TC
398
363
313
267
222
188
137
87
49
20
TDF-FTC
399
361
321
284
236
204
160
104
65
23
Sax PE, et al. NEJM 2009;361:2230-2240.
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ACTG 5202: Wirksamkeit zu Woche 96
HIV RNA <100,000 K/ml
CD4-Veränderung/µl
P=
# 59LB Darr E et al
Alle Patienten
250
251
0.89
252 221
0.002
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ACTG 5202
ATV/r > EFV – mehr NNRTI- und NRTI-Mutationen
ABC/3TC = TDF/FTC
# 59LB Darr E et al
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ACTG 5202: ATV/r vs. EFV
Mittlere Veränderung Lipide und Kreatininclearance
Median Change in Fasting Lipids (Week 48, mg/dL)
TC
LDL
HDL
TG
ATV/r
29
13
8
24
EFV
40
21
12
15
<0.001
0.002
<0.001
0.26
ATV/r
10
2
5
14
EFV
22
10
8
13
<0.001
0.002
<0.001
0.26
ABC/3TC
P-value
TDF/FTC
P-value
In low HIV RNA stratum, in comparison between ABC/3TC vs. TDF/FTC: significantly greater increase in
TC, LDL, HDL with both EFV and ATV/r; greater increase in TG with ATV/r
Change in Calculated Creatinine Clearance, (mL/min)
Week 48
Week 96
ATV/r
3.1
6.1
EFV
4.3
7.8
P-value
0.17
0.33
ATV/r
-0.9
-2.6
EFV
4.1
4.9
0.001
<0.001
ABC/3TC
TDF/FTC
P-value
Daar E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 59LB.
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ACTG 5202
EFV > ATV/r – Erhöhung von TC, LDL, HDL
VL <100.000 ABC/3TC > TDF/FTC Erhöhung von TC, LDL, HDL
# 59LB Darr E et al
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ACTG 5202
# 59LB Darr E et al
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ACTG 5224S
• Substudie von ACTG 5202
• n = 269, 47% weiß
• Knochen:
– DEXA: Woche 0, 24, 48, 96, dann jährlich
• Fettverteilung:
– CT Abdomen: Woche 0 und 96
# 106LB McComsey G et al
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A5224s: Mean Percent Change in Lumbar
Spine Bone Mineral Density (Week 192)
NRTI Component:
Primary Analysis
EFV
ATV/r
Lumbar Spine percent BMD
change from week 0 to 192
ABC/3TC TDF/FTC
NNRTI/PI Component:
Secondary Analysis
P=0.004
•
•
P=0.035
Hip BMD: Significantly greater percent decline with TDF/FTC than ABC/3TC;
not significant for NNRTI/PI
No significant difference in fracture rate between arms
McComsey, G, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 106LB.
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ACTG 5224s: Limb Fat Changes
% Limb fat loss
from 0 to 96
weeks
TDF/FTC
+EFV
(n=56)
TDF/FTC
+ATV/r
(n=45)
ABC/3TC
+EFV
(n=53)
ABC/3TC
+ATV/r
(n=49)
Total
(n=203)
≥ 10%
Primary endpoint
14.3%
(6.4%,25.3%)
15.6%
(7.0%,28.6%)
18.9%
(9.4%, 31.6%)
16.3%
(7.5%,28.8%)
16.3%
(11.8%, 22.0%)
8.9%
0%
3.8%
6.1%
4.9%
≥ 20%
Post hoc
•
•
•
No statistically significant differences incidence of 10% and >= 20% loss of limb
fat between NRTI components and NNRTI/PI components (Fisher’s exact test)
Most study subjects gained limb fat; ATV/r increased limb/trunk fat more than
EFV
Study confirms the very low rate of lipoatrophy with these regimens
McComsey, G, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 106LB.
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Design ODIN-Studie
Treatment Phase (up to 48 weeks)
• ARV-Experienced
patients, aged
≥ 18 years
• HIV-1 RNA >
1000 copies /mL
• CD4 count >
50 cells /mm3
• No DRV Rams at
screening*
• Stable HAART for
≥ 12 weeks
590 patients
randomized
DRV/r 800/100mg QD
+ OBR (≥ 2 NRTIs )‡ (N=294)
DRV/r 600/100mg
+ OBR (≥ 2 NRTIs )‡ (N=296)
Patients Stratified
by screening HIV-1 RNA
(≤50,000, > 50,000 copies / mL)
* DRV RAMs include the following mutations: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V
‡ Individualized OBR included 2 N(t)RTIs based on ARV history and resistance testing
Cahn P, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 57
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ODIN: Baseline Charakteristika
Once - daily
DRV/r 800/100mg
(N=294)
Two - daily
DRV/r 600/100mg
(N=296)
NRTIs: ≥ 3
174 (59.1)
164 (55.4)
NNRTIs: ≥ 1
258 (87.8)
258 (87.2)
Pls: 0
135 (45.9)
137 (46.3)
Pls: 1
74 (25.2)
77 (26.0)
Pls: ≥ 2
85 (28.9)
82 (27.7)
248 (85.2)
247 (86.1)
19 (6.6)
15 (5.3)
1
53 (18.3)
75 (26.4)
≥2
218 (75.2)
194 (68.3)
0.5 (0.1-1.8)
0.5 (0.1-1.9)
PI RAMS
3 (0-13)
4 (0-14)
Primary PI mutations
0 (0-5)
0 (0-4)
Previous ARV Experience*, n (%)
Sensitivity to ≥8 Pls
Optimized Background therapy, n (%)
Number of active NRTIs used
0
Median (range) DRV fold-change
Median (range) mutations at baseline
Cahn P, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 57
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ODIN: Wirksamkeit und Resistenz
72.1%
70.9%
Difference in response qd vs bid
ITT: 72.1-70.9=1.2% (95% CI=-6.1%, 8.5%)
PP: 73.4-72.5=0.9% (95% CI=-6.7%, 8.4%)
Once-daily
DRV/r 800/100mg (N=294)
Twice-daily
DRV/r 600/100mg (N=296)
59
41
Loss of susceptibility to DRV
1 (1.7)
0
Loss of susceptibility to any PI
2 (3.4)
0
Loss of susceptibility to any NRTI in OBR
7 (11.9)
4 (9.8)
Number of patients, n (%)
Paired baseline/endpoint phenotypes
Cahn P, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 57
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ODIN: Sicherheit
Treatment-emergent grade
2-4 lipid and liver related
laboratory abnormalities
(≥22% incidence)
Once-daily DRV/r
800/100mg
(n=294)
Twice-daily DRV/r
600/100mg
(n=296)
P value
Triglycerides
5.2%
11.0%
<0.014
Total Cholesterol
10.1%
20.6%
<0.0007
LDLc Cholesterol
9.8%
16.7%
<0.019
• Once-daily DRV/r 800/100mg was effective and non-inferior to DRV/r
600/100mg bid in treatment-experienced HIV-1-infected patients with no
DRV RAMs (and limited overall resistance)
• The incidence of grade 2–4 lipid elevations with once-daily DRV/r
800/100mg was approximately half that of DRV/r 600/100mg bid
Cahn P, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 57
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EuroSIDA Study: Risiko für chronische Nierenerkrankung
• Analysis of patients with ≥3 creatinine measurements +
body weight, 2004
– 6,842 patients with 21,482 person-years of follow-up
• Definition of CKD (eGRF by Cockcroft-Gault)
– If baseline eGFR ≥60 mL/min/1.73 m2, fall to <60
– If baseline eGFR <60 mL/min/1.73 m2, fall by 25%
• 225 (3.3%) progressed to CKD
Cumulative Exposure to ARVs and Risk of CKD
Univariable
Multivariables
IRR/year
95% CI
P-value
IRR/year
95% CI
P-value
Tenofovir
1.32
1.21-1.41
<0.0001
1.16
1.06-1.25
<0.0001
Indinavir
1.18
1.13-1.24
<0.0001
1.12
1.06-1.18
<0.0001
Atazanavir
1.48
1.35-1.62
<0.0001
1.21
1.09-1.34
0.0003
Lopinavir/r
1.15
1.07-1.23
<0.0001
1.08
1.01-1.16
0.030
• Risk factors for CKD on TDF: age, HTN, HCV, lower eGFR, lower CD4+ count
Kirk O, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 107LB.
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HOPS-Kohorte: Mehr Frakturen bei HIV-Infizierten
• Comparison of HOPS cohort
(n=8456) vs National Hospital
Discharge Survey and National
Hospital Ambulatory Care Medical
Survey
–
Adjusted for age and gender
Gender-adjusted rates of fracture
among adults aged 25-54 years
HOPS*
P = 0.01
• Fractures: 276 during median
4.8 yrs follow-up
• Risk factors for fractures
–
–
–
–
–
Age >47
Nadir CD4+ count <200
HCV co-infection
Diabetes
Substance use
NHAMCS-OPD
P = 0.32
• Conclusion: Fracture rates are
higher in HIV infected population
and rate is increasing with age
* Indirectly standarized using rtes from NHAMCS-OPD data
Dao C, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 128.
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WIHS-Kohorte: Frakturen bei Frauen
•
•
Retrospective analysis of 1728 HIV+ and 663 HIVFractures at hip, spine, wrist or other site
–
•
Demographics (HIV+)
–
•
Ever or within past 6 months
56% black, median age = 40, BMI = 28
Medical History (HIV+)
–
–
Smoking 45%, Vitamin D supplements 42%, Menopause 20%, HCV+ 25%
CD4+ count = 482
–
On ARVs – 66%; Median
years ART 5 +/- 10
HIV +
HIV -
No. Incident
Fracture (%)
Fracture/
100 py
No. Incident
Fracture (%)
Fracture/
100 py
P-value
Any Site
148 (9%)
1.79
47 (7%)
1.41
0.13
Spine
15 (1%)
0.18
7 (1%)
0.21
0.92
Hip
15 (1%)
0.18
4 (1%)
0.12
0.32
Wrist
25 (1%)
0.29
11 (1%)
0.32
0.94
Other
105 (6%)
1.25
35 (4%)
1.04
0.29
Yin M, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 130.
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Vitamin D in Swiss Cohort Study
• Retrospective seasonal
analysis of Vitamin D
deficiency within Swiss cohort
• Started ARV in: Fall (n=108);
Spring (n=103)
– 75% men; age = 37;
White = 87%; CD4+ 227;
BMI = 22.9
– ARVs: TDF – 17%;
NNRTIs – 43%; PI -56%
• Conclusions
– Vitamin D deficiency is
common, but seasonal
– Blacks are at increased risk
– NNRTI use a risk factor
Vitamin D Deficiency is Not Influenced
By ART
Fall
(n=108)
Spring
(n=103)
14%
42%
Insufficiency
62%
53%
Target Level
24%
5%
14%
47%
Insufficiency
63%
48%
Target Level
23%
5%
18%
52%
Insufficiency
59%
38%
Target Level
23%
10%
Baseline before cART
Vitamin D Deficiency
12 Months after cART Start
Vitamin D Deficiency
18 Months after cART Start
Vitamin D Deficiency
Deficiency
Target
Mueller N, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 752.
<30 nmol/L
≥75 nmol/L
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Vitamin D in Swiss Cohort Study
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Cancer Incidence in AIDS patients




Cancer type
Study of cancer risk in AIDS
patients from 1980-2006
(n=372,364)
Predominantly male (79%),
non-hispanic black (42%),
MSM (42%)
Median age of 36 years at
the onset of AIDS
Cancer risk in years 3 - 5
after AIDS onset increased
for AIDS but also Non-AIDS
defining cancers
Simard E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 27.
No cases
SIR
95% CI
Kaposi sarcoma
3136
5321
5137 - 5511
Non-Hodgkin
lymphoma
3345
32
31 - 33
Cervical cancer
101
5.6
5.5 - 6.8
AIDS-defining cancers
Non-AIDS-defining cancers
Anal cancer
219
27
24 - 31
Liver cancer
86
3.7
3.0 - 4.6
Lung cancer
531
3.0
2.8 - 3.3
Hodgkin lymphoma
184
9.1
7.7 - 11
All non-AIDS related
cancers
2155
1.7
1.5 - 1.8
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Cancer Mortality in AIDS patients
Population attributable risk among people with AIDS in the US
Simard E, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 27.
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Immunodeficiency and
Non-AIDS Related Cancer
•
•
Predominantly male (90%), white (56%), MSM (75%), mean age of 40 years
Cancer related risk factors:
– Smoking 39%, Overweight 39%, Alcohol abuse 19%,
–
HCV-infected 8%, HBV-infected 5%
•
Crude incidence rates and adjusted hazard ratios infection-related Non-AIDS
defining cancers
HIV +
HIV-
Adjusted Hazard
Ratio (95% CI)‡
n
rate†
n
rate†
215
267
284
28
5.9 (4.7-7.5)
Anal
140
174
21
2
74.9 (46.8-120.0)
Hodgkin’s lymphoma
44
54
29
3
17.7 (10.6-29.7)
Oral Cavity/pharynx
35
43
162
16
1.7 (1.1-2.5)
Liver
21
26
94
9
0.6 (0.4-1.0)
Any
† cases per 100,000 person-years;
‡ Adjusted per age, sex, tobacco use, overweight/obese, alcohol/drug abuse, hepatitis B/C
Silverberg et al. CROI 2010 Abstract 28
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Immunodeficiency and
Non-AIDS related cancer
• Crude incidence rates and adjusted hazard ratios non-infection-related
Non-AIDS defining cancers
HIV +
HIV-
n
rate†
n
rate†
Adjusted Hazard
Ratio (95% CI)‡
373
465
3.418
341
1.3 (1.1-1.4)
Melanoma
48
59
359
35
1.8 (1.3-2.5)
Kidney
16
20
126
12
1.4 (0.8-2.4)
Blood
16
20
141
14
1.3 (0.8-2.3)
Lung
51
63
342
34
1.2 (0.9-1.7)
Colorectal
41
51
410
40
1.1 (0.8-1.6)
Prostate
74
101
1,195
131
0.8 (0.6-1.0)
Any
† cases per 100,000 person-years;
‡ Adjusted per age, sex, tobacco use, overweight/obese, alcohol/drug abuse, hepatitis B/C
Silverberg et al. CROI 2010 Abstract 28
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Effect of non-SVR on Risk of New ADC
and Non–Liver-Related Death
Factors Associated with Liver Related
Events by Cox Regression Analysis
Adjusted
HR (95%
CI)
Factor
Effect of non-SVR on Risk of New ADC and NonLiver Related Death by Cox Regression Analysis
8.92
(1.20-66.11)
.032
F3-F4
vs F0-F2
4.96
(2.27-10.85)
.000
Geno 1-4
vs 2-3
1.35
(0.63-2.88)
.443
HCV RNA
<500K IU/mL
0.73
(0.33-1.62)
.444
CDC
category C
vs A/B
0.95
(0.49-1.87)
.327
0
1
10
0.99
100
(0.99-1.00)
P
3.60 (1.14-
Non-SVR
vs SVR
Nadir CD4
cells
HR (95% CI)
P
New ADC
9.21)
.008
3.24 (1.08-
.06
9.74)
.319
3.50 (1.22Non-liverrelated
death
10.0)
.019
2.60 (1.63-
.135
6.68)
New ADC
and nonliverrelated
death
0
1
Liver-related events include: liver-related death, lever
decomposition,
hepatocellular
carcinoma
Berenguer,
J. et al. Hepatology
2009;50:407-413;
Berenguer,, J,and
et al.transplantation
17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 167.
10
3.30 (1.636.68)
2.86 (1.24-
 Crude
.001
 Adjusted
.013
6.55)
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•
•
•
•
Retrospective study of 70
HIV-infected patients with
HCV-related HCC (1992-2009)
Patients considered screened (n=39) if
initially presented with an abnormal
AFP level or liver imaging study, and
not screened if they presented with
symptoms
No significant differences between
screened and non-screened patients
regarding age, race/ethnicity, median
HIV RNA level or median CD4+ cell
count
Screened patients were more likely to
present with earlier HCC stages and
lower HCC staging score and to have
longer time to mortality
Nunez, M, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 685.
Cumulative Survival
Screening for Hepatocellular Carcinoma in
HIV/HCV-Coinfected Patients
p=0.021
At Risk
HCC Screen
39
1
10
No HCC Screen
31
Actuarial median survival:
HCC screen
12.8 months
No HCC screen
3.7 months
5
3
0
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Life Expectancy of
HIV-Positive Patients
Comparison of life expectancy of Athena
cohort patients to general population
–
–
–
•
•
•
Enrolled those in ATHENA without AIDS Dx and
did not start therapy for at least 24 weeks and
excluded those with IDU
Included 4174 patients with 17,580 years of
follow-up all diagnosed after 1998
3710 men; median CD4 at 24 weeks 480 cells/mm 3
Age at week 24, country of birth and stage B
symptoms were associated with a higher risk
of death
Expected life years remaining at age 25 was
53.1 (44.9-59.5) for general population and
52.7 for asymptomatic HIV+ patients
The modeled life expectancy of patient
presenting at an older age and women
were slightly lower that general population
van Sighem A, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 526.
Years of Life Remaining
Age at time of death
Years lived
•
Remaining Life Years
Age at 24 weeks (years)
General Population
Asymptomatic HIV+ Patients
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Impact of Treatment Intensification on
HIV Reservoirs and Immune Activation
•
RAL or T20 intensification in patients with suboptimal CD4 response 
no effect1,2
•
Increase in episomal cDNA following RAL intensification  suggest
active replication persist in some HAART suppressed patients (~ 29%).
Correlated with decrease
in immune activation3
•
MVC intensification of suppressive HAART  no effect on levels of
immune activation and CD4 depletion in GALT4
•
MVC intensification of suppressive HAART in patients with suboptimal
CD4 response  no increase in CD4
but decrease in immune activation and improvement of markers of
apoptosis5
1. Hatano H, et al. 17th CROI; San Francisco, CA, US; February 16-19, 2010. Abst. 101LB; 2. Joly V, et al. ibid. Abst. 282; 3. Buzon MJ, et al.
ibid. Abst. 100LB; 4. Evering T, et al. ibid. Abst. 283; 5. Wilkin T, et al. ibid. Abst. 285.
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Early Initiation of Antiretroviral Therapy in HIV-Infected
Individuals is Associated with Reduced Arterial Stiffness
•
•
Cross-sectional study assessing effect of
earlier ART on CV risk
Enrolled 80 HIV-infected men on ARV Tx
with undetectable HIV RNA
–
–
–
•
•
Significant determinants of PWV
on Multivariate Analysis
SCOPE study treated in the chronic phase of HIV
infection (N = 65)
OPTIONS patients begin antiretroviral therapy
within 6 months of HIV diagnosis. (N=15)
Median age 47 years, nadir CD4+ T cell count 180
cells/mm3
Patients evaluated for CV risk by
assessment of arterial stiffness by pulse
wave analysis and carotid-femoral pulse
wave velocity
Multivariable Predictors of Pulse wave
velocity controlled for cardiovascular risk
factors, HIV treatment duration and current
CD4
Ho J, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 707.
Beta (95%)
P-value
Age
0.48
(0.26-0.70)
<0.001
Systolic blood
pressure
0.44
(0.12-0.76)
0.007
Diastolic blood
pressure
-0.29
(-0.53-0.04)
0.03
Diabetes mellitus
2.38
(1.38-3.38)
<0.001
Nadir CD4 <350
0.58
(0.15-1.01)
0.008
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Higher CD4 Nadir Associated with Less
Neurocognitive Impairment
Odds Ratio for Cognitive Impairment by CD4 Nadir
Odds Ratio
• Neurocognitive disorders
assessed in the
CHARTER prospective
observational study
– 1525 patients, 589 on
ARV therapy
• 603 had HAND (without
a substantial
confounder);
726 not impaired
• Most with hand (n=428)
were asymptomatic and
only a few (n=27) had
frank dementia
1.1
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
<50
50-199
CD4 Nadir
200-349
≥350
Odds Ratios for NP Impairment
N
Impaired
Unimpaired
1525
799
726
Nadir CD4 < 50
387
222
165
1.00 (reference)
Nadir CD4 50-199
481
258
223
0.86 [0.66, 1.13]
Nadir CD4 200-349
370
189
181
0.78 [0.58, 1.03]
Nadir CD4 ≥350
287
130
157
0.62 [0.45, 0.84]
589
320
269
Nadir CD4 < 50
185
112
73
1.00 (reference)
Nadir CD4 50-199
214
118
96
0.80 [0.54, 1.19]
Nadir CD4 200-349
133
64
69
0.60 [0.39, 0.95]
57
26
31
0.55 [0.30, 0.99]
All
On ART, Plasma VL <50c/ml
Nadir CD4 ≥350
Ellis R, et al. 17th CROI; San Francisco, CA; February 16-19, 2010. Abst. 429.
OR (95% CI)
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