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

RV

October 20, 20091

V 144 RV 144

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Trial Objectives and Design

Demographics

ResultsResults

October 20, 20092

V 144 Trial Objectives

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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

RV

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

RV

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 RV 144

RV

Trial Objectives and Design

Demographics

ResultsResults

October 20, 20099

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 

RV

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

RV

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

RV

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

RV

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 RV 144

RV

Trial Objectives and Design

Demographics

ResultsResults

October 20, 200918

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