Transcript Document

S•M•A•R•T
Limitations of Current
Antiretroviral Therapy
• Inability to eradicate HIV
• Limited number of agents/classes
• Development of HIV resistance
• Occurrence of serious side effects
• Difficulty with long-term adherence
S•M•A•R•T
Basis for Antiretroviral Guidelines
•
•
•
Short-term trials
Observational studies
Expert opinion
Only partially evidence-based
S•M•A•R•T
2001 DHHS Guidelines
Clinical Category
CD4+ Count
Plasma HIV
RNA
Symptomatic
Recommendation
Treat!!
Asymptomatic
< 200/mm3
Any
Treat!
Asymptomatic
> 200/mm3
and < 350/mm3
Any
Treat. But…
Asymptomatic
> 350
> 55,000
Treat?
Asymptomatic
> 350
< 55,000
Treat??
S•M•A•R•T
A Large, Randomized Trial
Comparing Two
Strategies for
Management of
AntiRetroviral
Therapy
S•M•A•R•T
The SMART Study is a:
Multicenter Study of the
Terry Beirn Community Programs for Clinical
Research on AIDS (CPCRA)
Funded by:
NIH: The National Institute of Allergy and
Infectious Diseases
Division of AIDS
S•M•A•R•T
Countries Participating in SMART
CPCRA
RCC
Sydney
RCC
Brazil
Canada
Peru
South Africa
United States
Argentina
Australia
Chile
Israel
Japan
New Zealand
Thailand
Uruguay
Copenhagen
RCC
Austria
Belgium
Denmark
Estonia
Finland
Germany
Lithuania
Luxembourg
Norway
Poland
Portugal
Russia
Spain
London
RCC
France
Greece
Ireland
Italy
Morocco
Switzerland
United Kingdom
S•M•A•R•T
SMART Study Design
Participants with CD4+ > 350
n = 3000
Virologic Suppression
(VS) Strategy
[Use ART to maintain viral
load as low as possible
throughout follow-up]
n = 3000
Drug Conservation
(DC) Strategy
[Stop or defer ART until CD4+
< 250; then episodic ART
based on CD4+ cell count to
increase counts to > 350]
Expected follow-up period: 7-8 years
S•M•A•R•T
The SMART Study Questions
• What is the optimal way to use ART to achieve
longest disease-free survival?
• Which treatment strategy is associated with
– Better adherence
– Fewer drug side effects
– Fewer metabolic complications
– Better quality of life
– Less drug resistance?
• Which strategy is more cost effective?
S•M•A•R•T
Study Treatment Comparison
Viral Suppression Strategy
Continuous Antiretroviral Therapy
VS
Drug Conservation Strategy
Episodic Antiretroviral Therapy
S•M•A•R•T
Primary Objective
To compare the VS and DC
strategies in prolonging survival
without progression of disease.
S•M•A•R•T
Other Major Clinical Outcomes
• Death
• Major cardiovascular and metabolic
complications
• Serious HIV progression events
• Combined endpoint of death, HIV
disease progression, and major
cardiovascular and metabolic
events
• Grade 4 adverse events
S•M•A•R•T
SMART Target Population
• HIV-infected patients
• CD4+ cell counts > 350 cells/mm3
• Older than 13 years of age
• Willing to initiate, modify, or stop
antiretroviral therapy, in accordance
with the randomized assignment.
S•M•A•R•T
Viral Suppression (VS) Strategy
Goal
Maintain maximum possible suppression of
viral load
Treatment Strategy
Utilize any available HIV treatments
irrespective of CD4 cell count
S•M•A•R•T
Viral Suppression Strategy
Potential
BENEFITS
• Maximal suppression of
viral load more likely
Potential
RISKS
• More cumulative side effects
• Adherence more difficult
• Lower risk of resistance
due to viral suppression
• Resistance to more agents
with virologic failures
• Lower risk of lasting
CD4 depletion
• Fewer active anti-HIV agents
available when risk of disease
is higher
• Potential lower risk of
HIV transmission
S•M•A•R•T
Drug Conservation (DC) Strategy
Goal
Conserve anti-HIV drug options while the
risk of disease progression is low
Treatment Strategy
Defer use of anti-HIV agents until CD4 cell
count is < 250 then treat episodically to
maintain CD4 > 350 using any available
HIV treatments
S•M•A•R•T
Drug Conservation Strategy
Potential
BENEFITS
• Potent anti-HIV agents
available when risk of
disease increases
• Fewer side effects
• Less anti-HIV drug use
may reduce the risk of
drug resistance
Potential
RISKS
• Stopping and restarting
anti-HIV agents may
increase the risk of drug
resistance
• Risk of lasting damage to
immune system
• Potential increased risk
of HIV transmission
• Adherence may be better
with episodic therapy
S•M•A•R•T
SMART Participants and Timetable
• Enrollment from 8 January 2002 to 11 January 2006
–
33 countries
–
318 sites
–
5,472 patients
• Date randomization screens closed: 11 January 2006
• Mean follow-up: 15 months
S•M•A•R•T
Canadian Participation
• 13 sites across Canada
• First Canadian site opened in December
2004
• 10 of 13 sites were opened for enrolment
S•M•A•R•T
Canadian Enrolment
(to 11 January 2006)
Site
Enrollment
CHUL (Ste-Foy, Quebec)
Toronto Hospital (Ontario)
McMaster (Hamilton, Ontario)
Halifax (Nova Scotia)
CHUS (Fleurimont, Quebec)
Montreal Chest (Quebec)
Windsor (Ontario)
St. Joseph’s (London, Ontario)
L’actuel (Montreal, Quebec)
Medical Halles (Ste-Foy, Quebec)
14
5
8
9
13
4
7
4
29
9
Total =
102/150
S•M•A•R•T
Canadian Sites
Three sites not opened for enrolment:
• Quartier Latin (Montreal, Quebec)
• Sudbury (Ontario)
• DIDC (Vancouver, British Columbia)
S•M•A•R•T
Ja
nM
A
pr ar 2
-J 0
Ju u n 02
l-S 20
O ep 02
ct
-D 20
Ja ec 02
n- 2
0
A Mar 02
pr
-J 20
Ju u n 03
l-S 20
O ep 03
ct
-D 20
Ja ec 03
n- 2
0
A Mar 03
pr
-J 20
Ju u n 04
l-S 20
O ep 04
ct
-D 20
Ja ec 04
n- 2
M 00
A
pr ar 2 4
-J 0
Ju u n 05
l-S 20
O ep 05
ct
-D 20
ec 05
2
Ja 00
n 5
20
06
Total Number Enrolled
SMART Enrollment by Quarter
1000
900
800
700
600
500
400
300
200
100
0
Sydney RCC
London RCC
Copenhagen RCC
CPCRA RCC
240 243
250
186
153
170
292
240
942
623
503
547
293
351
195
117 127
S•M•A•R•T
Enrollment by Geographic Region
3%
3% 1%
10%
57%
North America
Europe
South America
Australia/NZ
Asia
Africa
26%
S•M•A•R•T
SMART Study: Enrollment Through
11 January 2006
Number Enrolled
Study
Main
DC
VS
Total
2720
2752
5472
S•M•A•R•T
Baseline Characteristics
Patients with data available as of 10 Dec 2005
DC Group
Number
VS Group
Total
2443
2464
4907
Age (years; mean)
46
46
46
Female (%)
25
27
26
Race:
Black (%)
White (%)
Other (%)
30
57
13
32
55
13
31
56
13
Likely mode of infection:
Sexual contact, same sex (%)
Sexual contact, opposite sex (%)
Injection drug use (%)
Other/ unknown (%)
53
42
10
8
50
44
10
9
52
43
10
8
S•M•A•R•T
Baseline Characteristics
Patients with data available as of 10 Dec 2005
DC Group
Number
VS Group
Total
IQR
2443
2464
4907
CD4+ (cells/mm3; median)
599
598
598
(466, 792)
CD4+ nadir (cells/mm3; median)
253
253
253
(153, 364)
HIV RNA ≤ 400 copies/mL (%)
69.8
69.4
69.6
HIV RNA < 1000 copies/mL (%)
74.3
73.9
74.1
4.8
4.8
4.8
Highest log HIV RNA
(log copies/mL; median)
S•M•A•R•T
Baseline Characteristics
Patients with data available as of 10 Dec 2005
DC Group
VS Group
Total
Number
2443
2464
4907
Prior AIDS-related illnesses (%)
24.4
23.4
23.9
Hepatitis B co-infection (%)
2.5
2.3
2.4
Hepatitis C co-infection (%)
16.1
14.9
15.5
S•M•A•R•T
Baseline Characteristics
Patients with data available as of 10 Dec 2005
DC Group
VS Group
Total
Number
2443
2464
4907
ART History
ART naïve (%)
PI experienced (%)
NNRTI experienced (%)
On ART at baseline (%)
4.7
68.9
64.6
83.3
5.1
66.5
64.3
82.5
4.9
67.7
64.5
82.9
6
6
6
Time since first prescribed ART
(years; median)
IQR
(3, 8)
S•M•A•R•T
Distribution of Baseline CD4+
Cell Count
1200
22%
No. of Patients
1000
21%
16%
800
12%
600
9%
400
8%
7%
5%
200
0
350+
450+
550+
650+
750+
850+
950+
1050++
CD4+ Count (cells/mm3)
Mean: 661
Median, [ 25th ; 75th ]: 598[ 466 ; 792 ]
S•M•A•R•T
Distribution of CD4+ Nadir
Prior to Enrollment
700
13%
No. of Patients
13%
600
11%
11%
500 10%
9%
9%
7%
400
7%
6%
300
4%
200
100
0
0+
50+
100+ 150 + 200+ 250+ 300+ 350+ 400+ 450+ 500+
CD4+ Nadir (cells/mm3)
Mean: 270
Median, [ 25th ; 75th ]: 253
[ 153 ; 364 ]
S•M•A•R•T
SMART Statistical Methods
• Intent-to-treat
• DC versus VS comparisons
–
Kaplan-Meier survival curves and Cox’s proportional
hazard models used to compare treatment groups for:
• Progression to AIDS or death
• Survival
• Major cardiovascular and metabolic events
• Serious disease progression events
• Grade 4 events
–
Data cutoff date used in clinical events analyses: 10
December 2005; at that time 5,007 patients were
randomized.
S•M•A•R•T
Follow-up by Treatment Group
Number of follow-up
visits missed (%)
Number lost to
follow-up (%)
Median months of
follow-up (IQR)
DC Group
761 (4.6%)
VS Group
1,061 (6.4%)
48 (1.9%)
55 (2.2%)
10 (4,23)
10 (4,23)
Average follow-up (months)
14.7
14.7
Total person years
through 10 Dec 2005
3062
3077
S•M•A•R•T
Hypothetical CD4+ Cell Count Patterns Over Follow-up
600
(a)
500
400
C D 4+
cell co unt300
200
DC Group
VS Group
100
0
0
1
2
3
4
5
6
7
3
4
5
6
7
3
4
5
6
7
600
(b)
500
400
CD4+
ce ll count
300
200
DC Group
VS Group
100
0
0
1
2
600
(c)
500
400
CD4+
ce ll count
300
200
DC Group
VS Group
100
0
0
1
2
Ye ar of Follow-up
Pos sible Pat terns of C D 4+ C ell C ount s D uring Follow-up f or the D C and VS group:
(a) no dif f erenc e in C D 4+ c ell count af ter 5 y ears ; (b) C D 4+ cell c ount in the D C and VS
group do not conv erge; and (c ) C D 4+ c ell count great er in the D C t han VS group af ter 5
y ears. For eac h of these pos sible patterns the long-term c linic al implic ations are unc ertain.
S•M•A•R•T
Confirmed Clinical Events+ - 1
through 10 December 2005
RR (DC/VS)
DC Group
VS Group
N
Rate
N
Rate
Progression of disease or
death (primary endpoint)
93
3.1
44
1.4
2.15 [1.50, 3.08]
<0.0001
Death
47
1.5
29
0.9
1.63 [1.02, 2.58]
0.04
Group I1 events
59
2.0
37
1.2
1.62 [1.07, 2.44]
0.02
Major CVD or metabolic
complications2
83
2.9
73
2.5
1.14 [0.83, 1.56]
0.41
+ Reviewed
[95% CI]
P-value
and adjudicated by Endpoint Review Committee
1
Fatal or non-fatal MI (reported as supplemental event or diagnosed by ECG), stroke, CAD requiring surgery,
kidney failure, cirrhosis.
2
Fatal or non-fatal MI (reported as supplemental event or diagnosed by ECG), CAD requiring drug treatment
S•M•A•R•T
or an invasive procedure, stroke, myocarditis, pericarditis, diabetes requiring drug treatment, pancreatitis,
lactic acidosis, osteonecrosis.
Time to Disease Progression or Death
Confirmed events through 10 December 2005
S•M•A•R•T
Time to Death
Events through 10 December 2005
S•M•A•R•T
SMART Primary Composite Endpoint (Disease Progression or
Death) and Components; Confirmed Events Through 10 Dec
Endpoints
No. of Patients
with Events
Progression of Disease or
Death
Relative Risk
(95% CI)
2.2
137
1.6
Death
76
5.8
Serious Progression Event
19
>
2.9
Serious Progression of
disease or death
46
1.9
91
0.1
1
►
Other Progression Event
Favors DC
10
S•M•A•R•T
Favors VS ►
Time to Group I Event1
Confirmed events through 10 December 2005
1
Fatal or non-fatal MI (reported as supplemental event or diagnosed by ECG), stroke, CAD requiring surgery,
kidney failure, cirrhosis.
S•M•A•R•T
SMART Group I Events and Components:
Confirmed Events Through 10 December
Subgroups
No. of Patients
with Events
Relative Risk
(95% CI)
1.6
Total
96
1.5
Cardiovascular
78
1.5
Liver
15
2.0
9
0.1
1
►
Renal
10
S•M•A•R•T
Favors DC
Favors VS ►
Confirmed Clinical Events+ - 2
through 10 December 2005
Serious progression of
disease1
Serious progression of
disease1 or death
Grade 4 events
Total follow-up time
(person-years)
RR (DC/VS)
DC Group
VS Group
N
Rate
N
Rate
16
0.5
3
0.1
5.82 [1.68, 20.2]
0.01
59
1.9
32
1.0
1.88 [1.22, 2.90]
0.003
157
5.4
133
4.5
1.19 [0.94, 1.49]
0.15
3062
[95% CI]
P-value
3077
+
Reviewed and adjudicated by Endpoint Review Committee.
1
Progressive multifocal leukoencephalopathy, lymphoma, visceral Kaposi’s sarcoma, AIDS dementia
S•M•A•R•T
complex, toxoplasmosis, histoplasmosis, cryptococcosis, MAC, wasting syndrome, cytomegalovirus
disease.
Rate of AIDS-related Illnesses
through 10 December 2005
AIDS – related event
Aspergillosis, invasive
Candidiasis, esophageal
Candidiasis of bronchi, trachea, or lungs
CMV disease
Cryptococcosis, extrapulmonary
Encephalopathy, HIV-related, stage 2 or higher
Herpes simplex
Herpes zoster, disseminated
Kaposi’s sarcoma
Lymphoma
TB, pulmonary or extrapulmonary
MAC, extrapulmonary
PCP
Pneumonia, bacterial3
Wasting syndrome due to HIV
Patients with any AIDS-related event
DC Group
Events1 Rate2
0
17
2
1
1
1
3
3
6
4
2
1
6
7
3
54
0
0.6
0.1
0.0
0.0
0.0
0.1
0.1
0.2
0.1
0.1
0.0
0.2
0.2
0.1
1.8
VS Group
Events1 Rate2
1
5
0
0
0
0
2
1
1
1
2
1
2
2
0
17
0.0
0.2
0
0
0
0
0.1
0.0
0.0
0.0
0.1
0.0
0.1
0.1
0
0.6
1
One patient may have several illnesses. Each occurrence is counted, but recurrent illnesses of the same type are counted only
once.
2
Per 100 person-years.
3
Recurred within 1 year.
S•M•A•R•T
Causes of Death
Deaths through 10 December 2005
Death Classification
DC Group
Deaths1 %
AIDS-related
Hepatic complications
Pancreatic/ GI complications
Cancer, excluding AIDS-related
Cardiovascular complications
Violent/ Accident
Other, none of the above2
Unknown
3
3
1
7
11
9
6
9
Total number of deaths
47 100.0
1
2
6.4
6.4
2.1
14.9
23.4
19.1
12.8
19.1
VS Group
Deaths1 %
1
4
0
5
10
9
2
2
3.4
13.8
0
17.2
34.5
31.0
6.9
6.9
29 100.0
Patients may have multiple causes of death.
Other includes the following causes: DC (cerebral empyema, renal failure – 2 patients,
ARDS/septic shock, bacterial meningitis, COPD/pneumonia) and VS
(intra-abdominal sepsis/multi-organ failure, pneumonia).
S•M•A•R•T
Progression of Disease or Death by Baseline CD4+
Confirmed Events Through 10 December 2005
% of
patients
CD4+ (cells in subper mm3)
group
DC Group
VS Group
Events Rate1
Events Rate1
RR2
(DC/VS)
[95%CI]
P-Value2
for RR
P-Value3
Interaction
0.07 350 - 449
0.30
21.7
21
3.36
17
2.40
1.4
[0.7,2.7]
450 - 549
20.4
23
3.80
6
0.96
4.0
[1.6,9.9]
<0.005
550 - 649
15.5
14
3.03
6
1.29
2.4
[0.9,6.2]
0.08
≥ 650
42.5
35
2.67
15
1.19
2.3
[1.2,4.1]
0.01
1 Per
100 person-years, time to first event.
proportional hazards model within subgroup
3 Subgroup by treatment group interaction, Cox proportional hazards model
2 Cox
S•M•A•R•T
Progression of Disease or Death for Baseline CD4+
Subgroups
Subgroups
Total
No. of Patients
with Events
Relative Risk
(95% CI)
2.2
137
CD4 (cells/mm3)
1.4
350 - 449
38
4.0
450 - 549
29
2.4
≥ 650
20
2.3
50
0.1
1
►
550 - 649
10
S•M•A•R•T
Favors DC
Favors VS ►
Progression of Disease or Death by Nadir CD4+
Confirmed Events Through 10 December 2005
Nadir CD4+
(cells per
mm3)
% of
patients
in subgroup
DC Group
VS Group
Events Rate1
Events Rate1
RR2
(DC/VS)
[95%CI]
P-Value2
for RR
P-Value3
Interaction
0.42
< 100
16.4
18
3.64
6
1.13
3.2
[1.3,8.2]
0.01
100-199
18.4
16
2.79
10
1.98
1.4
[0.6,3.1]
0.38
200-299
25.6
21
3.09
11
1.40
2.2
[1.1,4.6]
0.03
300-399
20.0
25
4.09
11
1.84
2.1
[1.1,4.4]
0.04
≥ 400
19.5
13
2.01
6
0.93
2.1
[0.8,5.6]
0.13
1 Per
100 person-years, time to first event.
proportional hazards model within subgroup
3 Subgroup by treatment group interaction, Cox proportional hazards model
2 Cox
S•M•A•R•T
Progression of Disease or Death for Nadir CD4+
Subgroups
Subgroups
No. of Patients
with Events
Relative Risk
(95% CI)
2.2
Total
137
Nadir CD4 (cells/mm3)
24
1.4
100 – 199
26
200 – 299
32
300 – 399
36
≥ 400
19
2.2
2.1
2.1
0.1
1
►
< 100
3.2
10
S•M•A•R•T
Favors DC
Favors VS ►
Progression of Disease or Death
by Baseline Viral Load for those on ART
Confirmed Events Through 10 December 2005
HIV RNA
(copies/mL)
% of
patients
in subgroup
DC Group
VS Group
Events Rate1
Events Rate1
RR2
(DC/VS)
[95%CI]
P-Value2
for RR
P-Value3
Interaction
<0.01
≤ 400
81.7
55
3.02
17
0.94
3.2
[1.9,5.6]
<0.005
> 400
18.3
19
3.04
18
2.85
1.1
[0.6,2.0]
0.87
1 Per
100 person-years, time to first event.
proportional hazards model within subgroup
3 Subgroup by treatment group interaction, Cox proportional hazards model
2 Cox
S•M•A•R•T
Progression of Disease or Death for Baseline HIV
RNA Subgroups among Those Taking ART
Subgroups
No. of Patients
with Events
Relative Risk
(95% CI)
2.2
Total
137
HIV RNA (copies/ mL)
(only patients on ART at baseline)
≤ 400
3.2
72
1.1
37
0.1
1
►
> 400
10
S•M•A•R•T
Favors DC
Favors VS ►
Percent of Patients on ART at each Month of
Follow-up and Treatment Group
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CD4+ Change from Baseline, Mean + 2SE
(in cells/mm3) by Month of Follow-up and Treatment Group
S•M•A•R•T
Hypothetical CD4+ Cell Count Patterns Over Follow-up
600
(a)
500
400
C D 4+
cell co unt300
200
DC Group
VS Group
100
0
0
1
2
3
4
5
6
7
3
4
5
6
7
3
4
5
6
7
600
(b)
500
400
CD4+
ce ll count
300
200
DC Group
VS Group
100
0
0
1
2
600
(c)
500
400
CD4+
ce ll count
300
200
DC Group
VS Group
100
0
0
1
2
Ye ar of Follow-up
Pos sible Pat terns of C D 4+ C ell C ount s D uring Follow-up f or the D C and VS group:
(a) no dif f erenc e in C D 4+ c ell count af ter 5 y ears ; (b) C D 4+ cell c ount in the D C and VS
group do not conv erge; and (c ) C D 4+ c ell count great er in the D C t han VS group af ter 5
y ears. For eac h of these pos sible patterns the long-term c linic al implic ations are unc ertain.
S•M•A•R•T
Percent with HIV RNA ≤ 400 copies/mL by Month of
Follow-up and Treatment Group
S•M•A•R•T
Summary - 1
• There is an increased risk in the DC
group compared to the VS group of:
–Progression to AIDS, including death
–Death
–Serious disease progression events
–Major cardiovascular, renal and liver
events
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Summary - 2
• The increased risk of the DC group compared to the VS
group did not differ according to subgroups defined by
baseline and nadir CD4+ cell count.
• For the subgroup of patients who entered with a viral load <
400 copies/mL on treatment, risk of progression was over 3fold higher in the DC group compared to the VS group.
• For other subgroups examined, risk was always greater in
the DC group than the VS group.
S•M•A•R•T
Conclusion of the SMART
executive committee
Episodic use of ART based on CD4+
cell count levels as per the SMART
study design is inferior to continuous
ART for the management of treatment
experienced patients and thus should
not be routinely recommended.
S•M•A•R•T
Questions:
• Do you agree with the conclusion of
the executive committee?
S•M•A•R•T
Questions:
• Do you agree with the DSMB's
recommendation to:
(a) stop enrolment?
(b) consider changing the therapy for
patients in the DC arm?
S•M•A•R•T
Questions:
• Given that the relative risks between
the 2 arms change over time, how
should patients who are 1 year into
the study be managed?
At 2 years? 3 years?
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Questions:
• Can the original question (long term
comparison) still be answered by, say, redesigning the study?
• If so, how? Any suggestions?
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SMART Baseline
CVD Risk factors (to Nov 2005)
Current smoker
41.8 %
Diabetes mellitus
7.6 %
Prior MI
1.8 %
Prior stroke
1.6 %
Peripheral vascular
disease
1.7 %
S•M•A•R•T
SMART Baseline
CVD Risk (cont.)
Major ECG abnormalities
7.9 %
Coronary artery disease
2.8 %
Congestive heart failure
0.9 %
Antihypertensive drugs
20.3 %
Cholesterol >= 240 or lipid
lowering drugs
23.3 %
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NIAID Stops Intermittent HAART Trial
Reuters Health Information 2006. © 2006 Reuters Ltd.
NEW YORK (Reuters Health) Jan 18 - The National Institute of Allergy
and Infectious Diseases has halted enrollment in a large international
trial comparing continuous highly active antiretroviral therapy (HAART)
with intermittent therapy, guided by CD4+ cell counts.
The trial, known as Strategies for Management of Antiretroviral therapy
(SMART), quickly showed that patients do better on continuous HAART,
according to a statement released by the NIAID on Wednesday.
Patients in the intermittent arm had twice the risk of dying or
progressing to AIDS. "Furthermore, there was an increase in major
complications such as cardiovascular, kidney and liver diseases in the
participants on the drug conservation arm," the statement continued.
"These complications have been associated with (HAART), and it was
hoped that they would be seen less frequently in those patients
receiving less drug," it added.
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NIAID Stops Intermittent HAART Trial
(Continued)
"We were surprised to learn that in the short-term, episodic
antiretroviral therapy carries such an increased risk without evidence of
sparing patients the known side effects associated with ART," said coinvestigator Dr. Wafaa El-Sadr of the Harlem Hospital Center and
Columbia University in New York.
The patients in the drug-sparing arm stopped treatment when CD4+
counts reached 350 cells per microliter and resumed treatment when
CD4+ counts dropped below 250 cells per microliter.
When the trial was stopped, it had enrolled 5472 of a target of 6000
patients at 318 clinical sites in 33 countries. The trial was halted
January 11, 2006 after an average follow-up of 15 months.
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