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V 144
V 14
4RV
ALVAC®‐HIV and AIDSVAX® B/E Prime‐Boost
RV
HIV‐1 Preventive Vaccine Regimen
Final Results of the Phase IIIFinal Results of the Phase IIICommunity‐based Trial in Thailand
Supachai Rerks‐Ngarm, Punnee Pittisutthithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Joseph Chiu, Merlin Robb, Robert Paris, Arthur Brown, Elizabeth Adams, Sanjay Gurunathan, Donald Francis, Chirasak Khamboonruang, Prasert Thongcharoen, Nelson L. Michael, Prayura Kunasol, Jerome Kim
for the MOPH‐TAVEG Collaboration
October 20, 20090Primary data to be published online by the New England Journal of Medicine 20 October 2009 at 1050 CET.
V 144 Trial Objectives
RV
Primary
To determine whether immunization with ALVAC ®‐HIVTo determine whether immunization with ALVAC HIV (vCP1521) boosted by AIDSVAX® B/E gp120 B/E protects Thai volunteers from HIV infection.
To determine effect of immunization on viral load after interTo determine effect of immunization on viral load after inter‐current infection.
Secondary
To determine effect of immunization on CD4 cell count after inter‐current infection.
To confirm the safety of this vaccine combination.
To evaluate whether participation is associated with behavior change increasing risk of HIV infection
October 20, 20093
change increasing risk of HIV infection.
V 144 Co‐primary Endpoints
RV
Acquisition Endpoint~50% reduction in the relative risk of infection50% reduction in the relative risk of infection
Viral Load Endpoint or early ViremiaViral Load Endpoint or early Viremia0.4‐log HIV RNA reduction
October 20, 20094
V 144 Study Vaccines
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ALVAC®‐HIV (vCP1521)
Recombinant canarypox vector vaccine genetically engineered to express HIV‐1 gp120 (subtype E: 92TH023) linked to the transmembrane anchoring portion of gp41g p gp(subtype B: LAI), and HIV‐1 gag and protease (subtype B: LAI).
AIDSVAX® B/E
Bivalent HIV gp120 envelope glycoprotein vaccine gp p g y pcontaining a subtype E envelope from the HIV‐1 strain CM244 and a subtype B envelope from the HIV‐1 strain MN
October 20, 20095
MN.
V 144 Design
RV
Community‐based, randomized, double‐blind, placebo‐controlled trial (vaccine: placebo 1:1)( p )
Volunteers: HIV negative, 18‐30 years of age
Excluded: chronic disease, pregnancy or breastfeeding
6‐month period of study vaccinations
HIV testing every 6 months for 3 years post‐vaccination
October 20, 20096
V 144 Vaccination and Follow‐up Schedule
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HIV test,HIV test,risk assessment and counseling
0 5 1 2 3 (time in years)
6‐month vaccination schedule
3 years of follow‐up (every 6 mo.)
0.5 1 2 3 (time in years)
ALVAC®‐HIV (vCP1521) priming at week 0, 4, 12, 24
AIDSVAX® B/E gp120 boosting at week 12, 24
October 20, 20097
AIDSVAX B/E gp120 boosting at week 12, 24
V 144 Important Milestones
RV 24 September 2003 Screening began
20 October 2003 First vaccination
30 December 2005 Enrollment completed
31 July 2006 Vaccination completed
July 2007 DSMB Interim Analysis (based on mITT statistical plan)
Spring 2009 Communication Plan finalized
Commitment to ensuring that the Thai people would be the first to learn the outcome
June 2009
irrespective of the final result
Study Follow‐up Complete
October 20, 20098
V 144 From Screening to Vaccination
RV
26,676 Initial Screen128 Not Referred
26,548 HIV Test
128 Not Referred
418 HIV seropositive8 780 Discontinued
17,350 Clinic Screen
8,780 Discontinued
948 Ineligible422 TB/Other Disease
Up to 45‐days
16,402 Randomized341 Female Reproductive66 Unavailable for 3.5 years119 Other
7 BaselineHIV PCR Positive
16,395 Infection Free
October 20, 200910
8,197 Vaccine
8,198 Placebo
V 144 Definition of Analytical Methods
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16,402 Randomized Intent‐to‐Treat (ITT)7 Baseline
HIV PCR Positive
16,395 Infection Free
M difi d I t t t T t8,197 Vaccine
8,198 Placebo
Modified Intent‐to‐Treat (mITT)
6,176All doses on schedule
6,366All doses on schedule
Per Protocol (PP)
October 20, 200911
schedule schedule
V 144 Baseline Demographics
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Gender Age
5033 5031
50
60
70
3633 370850
60
70 Vaccine
Placebo
3164 3167
20
30
40% Vaccine
Placebo2297 22672246 2244
20
30
40%
0
10
Male Female
0
10
18‐20 21‐25 26‐30
October 20, 200912
V 144 Baseline Demographics
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Marital Status
60
70Vaccine
Placebo
3353
4110
3338
4169
40
50
60 Placebo
20
30%
734 691
0
10
October 20, 200913Other: Widowed, Separated, Divorced
Single Married Other
V 144 Definition of Risk Behavior
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High Risk: Self‐assessment as high risk OR self‐report of one or more high‐risk behavior(s) in the previous six g ( ) pmonths
N dl h i O ti t t i t• Needle‐sharing
• STI symptoms
• Sex with HIV‐positive partner
• Occupation entertainment
• Occupation CSW
• Jail drug injection
• No condom use during high‐risk encounters
• Multiple sex partners
October 20, 200914
V 144 Baseline Demographics
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Vaccinen (%)
Placebon (%)n (%) n (%)
Sexual Partner Frequency
0 Sex Partners 1864 (22.7) 1801 (22.0)
1 Sex Partner 5428 (66.2) 5495 (67.0)
>1 Sex Partners 619 (7.6) 620 (7.6)
( ) ( )No Answer 280 (3.4) 273 (3.3)
Missing Value 6 (0.1) 9 (0.1)
Other Risk Behaviors (from a list of 8 criteria)
Same‐gender partner 184 (2.2%) 182 (2.2%)
October 20, 200915
Needle‐sharing 68 (0.8%) 65 (0.8%)
V 144 Definition of Risk Behavior
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Low RiskSelf‐assessment as low risk AND self report of no high‐riskSelf assessment as low risk AND self report of no high risk behavior in the previous six months
Medium RiskNeither low risk nor high risk (as defined above)
October 20, 200916
V 144 Baseline Demographics
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Risk Behavior
60
70 Vaccine
Placebo
3865 3924
0
50
60
2369
1963
22921982
30
40
%
10
20
October 20, 200917
0
Low Medium High
V 144 Safety and Reactogenicity
RV
80 Vaccine
5625 5685
60
70
80 Vaccine
Placebo
30
40
50
%
1175
309
1219
29510
20
30
309 295
0
Any AE Any SAE Any Tx‐related
October 20, 200919
The vaccine regimen was safe and well tolerated.
V 144
Acquisition Endpoint: Modified Intent‐to‐Treat (mITT)RV
1.0 .96Placebo
n (%
)
0 7
0.8
0.9
64
.84
.68V i
-1 In
fect
ion
0.5
0.6
0.7 .64
41
.58Vaccine
Vaccine infections: 51Placebo infections: 74p = 0 04lit
y of
HIV
-
0.3
0.4.38 .41
p = 0.04Efficacy: 31.2%95% CI (OBF): 1.1, 51.2Pr
obab
i
0 0
0.1
0.2 .15
PlaceboVaccine
October 20, 200920
0.0
YEARS0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
V 144 Acquisition Endpoint: Per Protocol (PP)
RV
1.0
n (%
)
0 7
0.8
0.9
.70
.80Placebo
-1 In
fect
ion
0.5
0.6
0.7
.49.52
.59Vaccine
lity
of H
IV-
0.3
0.4.25 .36
Vaccine infections: 36Placebo infections: 50p = 0 16
Pro
babi
l
0 0
0.1
0.2.08 Placebo
Vaccine
p = 0.16Efficacy: 26.2%95% CI: ‐13.3, 51.9
October 20, 200921
0.0
YEARS0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
V 144 Early Viremia Endpoint
RV
6 6Vaccined
5 5
Placebo0
Vira
l Loa
d
4 4X X
Log
10
2
3
2
3
M Vi l L d
1
2
1
2
VACCINE PLACEBO
Mean Viral LoadVaccine recipients: 4.3 log10Placebo recipients: 4.2 log10p = NS
October 20, 200922
Dx 3 wks 6 wks Average
V 144 Conclusions
RV
1. The observed vaccine efficacy in the mITT analysis was 31.2% [p = 0.04, 95% CI (OBF) 1.1, 52.1].[p , ( ) , ]
2. PP and mITT results were qualitatively consistent.
3. There is no difference in early viremia between vaccine and placebo recipients.
4. The vaccine regimen is safe and well tolerated.
5. Self‐reported behavioral risk was the same in vaccine and placebo groups.
October 20, 200923
V 144 Acknowledgements
RV
RV144 volunteers and community members
AFRIMS – US and Thai Component
Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH
Faculty of Tropical Medicine, Mahidol University
Global Solutions for Infectious Diseases
Henry M. Jackson Foundation for the Advancement of Military Medicine
Ministry of Public Health, Thailand
sanofi pasteur
U.S. Military HIV Research Program, Walter Reed Army Institute of Research; U.S. Army Medical Research and Materiel Command
October 20, 200924