AIDS VACCINE DEVELOPMENTThe Way ForwardThe Way Forward

Jean-Louis Excler, MDSenior Director, Medical Affairs

International AIDS Vaccine Initiative

HPV and HIV: Disease, Infection and VaccinationHPV and HIV: Disease, Infection and VaccinationLes Pensieres, Veyrier-du-Lac, 20-21 October 2008

Overview of Presentation

1. Current Status of AIDS Vaccine Development

2. The Scientific Challengesg

3. The Way Forward y

IAVI R&D: Scientific Priorities

Design, develop and advance to g , pefficacy trials a vaccine candidate that:

Elicits broadly neutralizingElicits broadly neutralizing antibodies against HIV;

Controls HIV infection as well as live attenuated SIV protects against pathogenic SIV challengepathogenic SIV challenge.

AIDS Vaccines: Global Clinical Pipeline October 2008AIDS Vaccines: Global Clinical Pipeline. October 2008

Candidate Science- DataCandidate Science-Hypothesis

Data

gp120 B/B or B/E Neut Ab vs. lab-adapted Phase III: NO EFFICACYgp(VaxGen) isolates of HIV

ALVAC (Sanofi) + gp120 B/E (Vaxgen)

CD4 helper responses + NA to lab isolates

Phase III - Thai trial - data by 2009B/E (Vaxgen) + NA to lab isolates 2009

Ad5: gag-pol-nef (Merck) Cell-mediated immunity Phase IIB – NO EFFICACY

DNA + Ad5 (VRC, NIH) CMI Phase II

25 others (DNA, vectors…) CMI Phase I

NONE Neutralizing Ab, Mucosal Immunity

TBD

Key Results: Incidence (95% CI) of HIV InfectionMITT population (males)MITT population (males)

Baseline Vaccine Placebo Relative IncidenceAd5 Titer V P (V:P)

≤1819-200

4.0 (2.5, 6.3)4.4 (1.9, 8.8)

4.0 (2.5, 6.2)2.2 (0.6, 5.5)

1.0 (0.5, 2.0)2.1 (0.6, 9.3)

201-1000>1000

( )6.1 (3.3, 10.2)4.4 (1.8, 9.1)

( )3.0 (1.2, 6.2)1.2 (0.2, 4.5)

( )2.0 (0.8, 5.9)3.5 (0.7, 35.0)

≤18 4 0 (2 5 6 3) 4 0 (2 5 6 2) 1 0 (0 5 2 0)≤18>18

4.0 (2.5, 6.3)5.1 (3.4, 7.3)

4.0 (2.5, 6.2)2.2 (1.2, 3.8)

1.0 (0.5, 2.0)2.3 (1.1, 4.7)

≤200 4 2 (2 8 6 0) 3 5 (2 3 5 2) 1 2 (0 7 2 1)≤200>200

4.2 (2.8, 6.0)5.4 (3.3, 8.2)

3.5 (2.3, 5.2)2.3 (1.0, 4.3)

1.2 (0.7, 2.1)2.4 (1.0, 5.8)

O ll 4 6 (3 4 6 1) 3 1 (2 1 4 3) 1 5 (0 9 2 4)

18 is the LOQ for the Ad5 titer assay; includes all HIV cases thru Oct 17, 2007Source: STEP Trial Efficacy Analyses HVTN Full Group Meeting November 7 2007

Overall 4.6 (3.4, 6.1) 3.1 (2.1, 4.3) 1.5 (0.9, 2.4)

Source: STEP Trial, Efficacy Analyses, HVTN Full Group Meeting, November 7, 2007

Adeno-5 SIV gag vaccine vs. SIV mac 239 NO PROTECTIONNO PROTECTION

Casimero, Shiver et al (Merck)

What about increased acquisition of HIV in the Merck trial?Merck trial?

The cause remains unclear based on post hoc analysis:The cause remains unclear based on post-hoc analysis:

Ad5 pre-existing immunity

Lack of circumcision (65% circumcised in <200 titer group; 40 %

circumcised in >200 Ad5 titer groupcircumcised in 200 Ad5 titer group

Other factors (possible role of Ad5 IC?)

STUDIES ONGOING TO ELUCIDATE THE CAUSESTUDIES ONGOING TO ELUCIDATE THE CAUSE

Why did the Merck vaccine fail to suppress viral load in subjects who subsequently became HIV infected??subseque t y beca e ected

What we learned:

SHIV vs. SIV Model in Monkeys: Analogous SIV vaccine also failed to significantly suppress viral load, while SHIV model wrongly predicted successAssays & Correlates: 75% of subjects who received the vaccine responded positively by validated ELISPOT assay beckons for better more predictivepositively by validated ELISPOT assay.......beckons for better, more predictive assaysCMI responses were to multiple epitopes (approximately 3-5/subject)

What we don’t know:

Whether antigen targets matched sequences of transmitted virus: Studies ongoingWhether the failure is due to:Whether the failure is due to:

Vector: Non-replicative, too weak?Antigenic inserts: gag-pol-nef are they the right ones?Combination of vector + inserts?Combination of vector + inserts?Concept: Can any CMI-based vaccine suppress viral load?

Vector Based AIDS Vaccines in Clinical Trials – October 2008

Vi l V t Ad iDNA vectorsClade C, electroporation IAVI-ADARC

Clade B, MVA* Epimmune

Viral Vectors- AdenovirusAd-5 (Clade B) Merck

Ad-5 (Clades A,B,C), [DNA] NIH-VRC, p

Clade B, MVA* GeoVax

Multiclade-A,B,C, Ad5* NIH-VRC

Multiclade ABC MVA* Karolinska

Ad-6 (Clade B) Merck

Ad-26 (Clade A) Harvard-NIAID

Adenovirus-35 (Clade A) Ad5* NIH-VRC GenVecMulticlade-ABC, MVA* Karolinska

Clade C Johns Hopkins

Clade B/C Changchun Baike

Adenovirus 35 (Clade A) Ad5 NIH VRC GenVec

Viral Vectors- PoxCanarypox (Clade B/E), gp120* Aventis

Clade C, NYVAC* EuroVac

Clade B- IL12, IL-15, peptide* Wyeth

Clade C, MVA* SAAVI

MVA* (Clade C) IAVI-India

MVA (Clade B),[DNA] GeoVax

MVA (Clade A/E), [DNA] WRAIR/Karolinska

Clade B U. Penn

Clade A, FPV* HNATRC

( ) [ ]

MVA (Clade B/C) Changchun Baike

NYVAC (Clade C)[DNA] EuroVac

Vaccinia [DNA] China CDC

[ ] = prime

* = boost

Vaccinia [DNA] China CDC

Vaccinia (Cocktail) St. Jude’s

FPV Clade A,E, [DNA] HNATRC

MVA [DNA ] Bavarian Nordic

Phase I: Comparison of Vector Based HIV VaccinesImmunogenicity: ELISPOT IFN gammaImmunogenicity: ELISPOT-IFN-gamma

DNA DNA DNA AAV MVA MVA MVA AdenoDNAOxford2mg

DNAADARC3X4mg

DNAVRC3X4mg

AAVTGC

1x1011

MVAOxford

5x107

MVAADARC2.5x108

MVATherion2.5x108

AdenoVRC1x1010

6% 17% 49% 20% 5% 62% 100% 46%

Percent Positive Responders

Geometric Mean: SFC/million and Range of Responses

35 69 109 130 57 130 80 101

31-40 66-73 44-598 54-385 41-79 55-275 39-193 52-29731-40 66-73 44-598 54-385 41-79 55-275 39-193 52-297

Vaccine response rate in vaccinees at peak post vaccination timepoint per trial; Core Laboratory generated data; GMT SFC and min max SFC for responders; background subtracted per 106 PBMCs.

Lack of Correlation: ELISPOT-IFNg & ProtectionLow Dose Repeated Intravaginal SIV ChallengeLow Dose Repeated Intravaginal SIV Challenge

1x10 6

1x10 7

1x10 3

1x10 4

1x10 5Control

DNA/MVA

Delta Nef

9000

∆Nef 9000

DNA/MVA 1x10 1

1x10 2

0 5 10 15 20 25 30 35 40Weeks after viremia

6000

7000

8000

VPXVPR

6000

7000

8000

3000

4000

5000

VPRVIFREVNEFTATENVGAG 3000

4000

5000

0

1000

2000

GAG

0

1000

2000

247.94 442.00 316.99 395.93 291.94 527.99 300.98 461.99 218.97 356.97 403.97 405.97

Paul Johnson (Harvard/NERPC)

IAVI Assessment: The Current Pipeline is Inadequate

P i h th i tl b i t t d i i li i ll di t d i itPrimary hypothesis currently being tested in pipeline is cell-mediated immunity

Overview of Presentation

1. Current Status of AIDS Vaccine Development

2. Scientific Challengesg

3. The Way Forwardy

Scientific Challenges: SummaryNo one ever said it would be easy !!!No one ever said it would be easy !!!

• HIV presents the most daunting set of scientific h ll f i l ichallenges for any viral vaccine

Genetic variabilityImmune evasionImmune evasionNarrow window of opportunityLack of understanding: Which antigens and immune g gcorrelates are protectiveLack of ideal animal modelETCETC

IAVI Resources: Vaccine Discovery & DevelopmentAIDS Vaccine ConsortiumAIDS Vaccine Consortium

• IAVI Vaccine Development Lab NeutralizingNeutralizing

AntibodyAntibodyConsortiumConsortium

Vector DesignVector DesignConsortiumConsortium(VEC)(VEC)

• IAVI Human Immunology Lab

P d

(NAC)(NAC)( )( )

• Product Development Infrastructure

Control of HIV/Control of HIV/• Network of Partner-Sites in Developing World

Control of HIV/Control of HIV/SIVSIV--Live AttenuatedLive AttenuatedConsortium (LAC)Consortium (LAC)

Developing World

HIV-1 Global Diversity: 2008

B

DCRF03_ABCRF10_CD

CRF17_A2DB

C

FH

CRF05_FDCRF07 BC

CRF12_BF

K

F2CRF08_BCCRF07_BC

AJ CRF02_AG

CRF11_cpx

CRF01_AE

CRF06_cpx

CRF09 cpxCRF13_cpx

CRF14 BG

CRF15_01B

G A2CRF04_cpx

CRF09_cpxCRF14_BG

CRF16_A2D0.10

Proof of Concept: Non Human Primate StudiesProtection against homologous SIV 239 challenge by live

attenuated (Delta-nef) SIV (LAC)

108108

107107

es

es

VaccineStrategy

Monkeys Protected(>3log suppression of

viral load)

Live 4/ 8 (9 %)

106106 SIVmac239∆nef vaccinated (n=4)SIVmac239∆nef vaccinated (n=4)

NA

copi

eaN

A co

pie

a

Live attenuated 74/78 (95%)

All other strategies 18/256 (7%)

Koff et al Nature Immunology

104

105

104

105

n of

vR

Nl p

lasm

an

of v

RN

l pla

sma Koff et al, Nature Immunology,

January 2006

103

10

103

10

naïve controls (n=4)

naïve controls (n=4)

tric

mea

per m

tric

mea

per m

102102

geom

etge

omet

0 4 8 12 16 20 24 28 32 36 40 44 48Weeks p.i.

0 4 8 12 16 20 24 28 32 36 40 44 48Weeks p.i.

Genetic Diversity: Impact on Vaccine EfficacyHeterologous challenge following SIVNef vaccinationHeterologous challenge following SIVNef vaccination

Can the mechanisms of protection elicited by SIVmac239∆Nef protect pagainst a heterologous E660 virus?

Difference between the viruses are less than HIV cross clade (e.g. C vs B)

Reynolds et al 2008 (IAVI LAC): Submitted- Journal of Experimental Medicine

Proof of concept: Protection (@2 log reduction of viral load) conferred by live attenuated SIV (delta-nef, 239) vs.

heterologous challenge (E660)es

es

107

108

107

108

NA

copi

eaN

A co

pie

a

106106

nefnef

n of

vR

Nl p

lasm

an

of v

RN

l pla

sma

104

105

104

105nefnaivenefnaive

tric

mea

per m

tric

mea

per m

103

10

103

10

geom

etge

omet

0 4 8 12 16 20 24 28 32 36 40

102

0 4 8 12 16 20 24 28 32 36 40

102

0 4 8 12 16 20 24 28 32 36 400 4 8 12 16 20 24 28 32 36 40

Weeks p.c.Weeks p.c.

Live attenuated SIV (delta-nef, 239) vs. heterologous challenge (E660): The devil’s in the details only 4/10 control infection(E660): The devil s in the details…..only 4/10 control infection

02092 (A*01)02092 (A*01)

107

108

107

108

lasm

ala

sma 88085 (A*01)

01022 (A*02)rhAO84 (A*02)01009 (A*11)

88085 (A*01)01022 (A*02)rhAO84 (A*02)01009 (A*11)

☨☨

106106

er m

l pl

er m

l pl 01009 (A 11)

rh2000 (A*11)02132 (B*08)01048 (B*08)

01009 (A 11)rh2000 (A*11)02132 (B*08)01048 (B*08)

☨☨

104

105

104

105

opie

s pe

opie

s pe 01003 (B*17)

01079 (B*17)84070 (A*01)

( * )

01003 (B*17)01079 (B*17)84070 (A*01)

( * )

103

10

103

10

RN

A co

RN

A co 02129 (A*01)

00001 (A*02)rh2046 (A*02)99003 (A*11)

02129 (A*01)00001 (A*02)rh2046 (A*02)99003 (A*11)

0 4 8 12 16 20 24 28 32 36 40

102

0 4 8 12 16 20 24 28 32 36 40

102

vv 99003 (A 11)rhAQ54 (A*11)03127 (B*08)97042 (B*08)

99003 (A 11)rhAQ54 (A*11)03127 (B*08)97042 (B*08)

0 4 8 12 16 20 24 28 32 36 400 4 8 12 16 20 24 28 32 36 40

Weeks p.c.Weeks p.c.00015 (B*17)01039 (B*17)00015 (B*17)01039 (B*17)

Other Scientific Challenges in AIDS Vaccine DevelopmentNo Ideal Animal Model; No Immune Correlates;

Which HIV Antigens are Required for Protection?Which HIV Antigens are Required for Protection?

Phase I/IISafety & Immunogenicity

SIVProtection

Phase II Screening Test of Concept (STOC) TrialsSafety & Immunogenicity Protection p ( )

Preliminary Efficacy

• ELISPOT ICS • Systematic analysis of Small trials (30 incident HIV• ELISPOT, ICS• Poly-functional analysis• Functional Assays (Viral

Inhibition Assay)

• Systematic analysis of vectors and antigens

Small trials (30 incident HIV infections) to detect suppression of viral loads of 1 log or greater

Inhibition Assay)

What do they mean?? SIV is not HIV and monkeys are not

l ?

Preliminary indications of potential efficacy will help guide product developmentpeople? guide product development

Efficacy Trialsy

Control of HIV: Human Natural History StudiesBreadth of Gag CD8 ResponsesBreadth of Gag-CD8 Responses

p<0.0001

107

A p<0.0001

p<0.0001

GAG

107

p=0.0163p=0.0072 ENVB

p=0.0155p=0.0456

r=-0.25p<0.0001105

106

Loa

d 105

106

r=0.17p<0.0001

Load

103

104Vira

l

103

104Vira

l

102

0 1 2 3 >3Number of Gag responses

102

0 1 2 3 >3Number of Env responses

Th b dth f th E ifiTh b dth f th G ifi The breadth of the Env-specific CD8 response is associated with higher viral load

The breadth of the Gag-specific CD8 response is associated with lower viral load

Kiepiela et al, Nature Medicine 2007

Natural History of HIV Infection and Vaccine DesignNatural History of HIV Infection and Vaccine Design

At least five gag mutations were needed to reduce viral load significantly Thisload significantly. This threshold might explain why a T-cell vaccine that induces immune responses againstQuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture. immune responses against

few Gag epitopes failed in a recent trial. Better results

i h b i d b imight be gained by targeting more epitopes.

Goepfert et al. J Exp Med 2008; 205: xxx

Control of HIV Infection: Clues from Elite Controllers

Acute HIVas

ma

Interquartile10 Million

es/m

l pla

60 000

ranges

part

icle

30,000

60,000

RN

A 12,000<50- 2,000

Spontaneous Control<2000 RNA Copies/ml:

Delayed progressionD d t i iDecreased transmission

Early Events:Vaginal Transmission

Scientific Challenge : Brief Window of Opportunity

Vaginal Transmission

“Lenti” in Lentiviruses = misnomerLenti in Lentiviruses misnomerInitial stage of infection = rapid!

Systemic I f tiInfection

ProductionPersistencePathologyA Haase et al

AIDS Vaccines: Global Update- October 2008Summary & IAVI AssessmentSummary & IAVI Assessment

• Successful development of an AIDS vaccine will likely require:Induction of broadly neutralizing antibodiesInduction of broadly neutralizing antibodiesControl of HIV as well as live attenuated SIV controls against homologous challenge e.g. as well as human “elite controllers”

• No candidate currently in the pipeline achieves these objectives

N d i d b d ELISPOT ill h l i i i did• New and improved assays beyond ELISPOT will help to prioritize candidates for development

• Success will likely require:Breakthrough in the solution to the HIV neutralizing antibody problemDevelopment of more potent vector(s) e g replicating viral vectorsDevelopment of more potent vector(s) e.g. replicating viral vectorsDetermination of the HIV antigenic inserts which must be included in a vaccine to confer protection against globally diverse subtypes of HIV

Overview of Presentation

1. Current Status of AIDS Vaccine Development

2. Scientific Challengesg

3. The Way Forwardy

Roadmap for Developing an AIDS VaccineRoadmap for Developing an AIDS Vaccine

Solving theNeutralizingAntibody P bl

Solving theProblem of

How to ControlHIV I f tiProblem HIV Infection

Scientific Challenge #3: HIV Env Mediated Immune Evasion

Th h ll f li iti b dl t li i AbViral membrane

The challenge of eliciting broadly neutralizing Abs

MPER (4E10, 2F5, Z13e1)

CD4bs (b12)CD4bs (b12)

Glycan shield (2G12)

D. R Burton, R.L Stanfield, I.A. Wilson, 2005, PNAS 102:14943-8. C. C. Huang, et al., 2005, Science 310:1025-8.

Neutralizing Antibody Consortiumeu a g body Co so uBroadly neutralizing

antibodiesHigh thru-put immunogen

d iantibodies

Determining structure

of novel antigens

design

Assays to rapidly screen immunogens

Characterize

of novel antigens

Sera andIdentify BN-Mabs

ClinicalDev.

ImmunogenScreening

ImmunogenDesign

StructuralBiology

Proteins

Protocol GHigh

thru-putRobot

ProteinsPeptidesSugars

“needle inhaystack”

Major BlockSlow

ImmunogenScreenhaystack

IAVI Protocol G: The Search for New Broadly Neutralizing HIV-MAbs to Facilitate AIDS Vaccine DiscoveryMAbs to Facilitate AIDS Vaccine Discovery

Purpose: To generate novel potent and broad neutralizing monoclonal antibodies (bnMAbs) from HIV infected subjects who have broadly neutralizing(bnMAbs) from HIV infected subjects who have broadly neutralizing serum activity

Methods: Screen HIV infected individuals for broadly neutralizing serum activityMethods: Screen HIV infected individuals for broadly neutralizing serum activity• Key issue: Validated screening assay

Select subjects with broad and potent neutralization activity• Key Issue: Cohorts in the developing worldKey Issue: Cohorts in the developing world

Derive bnMAbs from their PBMCs•Key Issue: Multiple technologies to increase the chances of success

St d l tiStudy population:N=1000-2000Adults infected with HIV at least 3 yearsWith t d d diWithout advanced diseaseNot on ARTNon-B clades prioritized

Protocol G Research Partners

St. Stephen’s Centre

London, England

VTC & AFIRMS

SUNY-Brooklyn, United States

Bangkok, Thailand

C DR S Abidj

KAVI Nairobi,

CeDReS Abidjan, Côte d’Ivoire

MRC-UVRI Entebbe,

,Kenya

Emory ZEHRP

DTHF Cape Town, South Africa

PSF Kigali, Rwanda

Uganda

NSRL Victoria AustraliayLusaka, Zambia

NSRL Victoria, Australia

What if…..current efforts on the Neutralizing Ab Problem fail??

“Insanity: doing the same thing over and overInsanity: doing the same thing over and over again and expecting different results”

-Albert Einstein

I ti ill b k t !!!!Innovation will be key to success!!!!........

The Way Forward: Innovative ResearchA Novel Approach to Eliciting Broadly Neutralizing AntibodiesA Novel Approach to Eliciting Broadly Neutralizing Antibodies

Identify broadly li i l lneutralizing monoclonal

antibodies (MAb)

Insert MAb genes into vector (AAV)( )

Inject vector (AAV) into body

Express and maintain antibody l l ilevels over time

Phil J h t l NACPhil Johnson et al. NAC

Vector Mediated Ab Gene TransferProtection Against SIVg

678

678

Naive 4L6

3456

05C00905D01605D225

3456

05C02005C06605D014

(log 1

0)

012

012

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0 2 4 8 0 2 4 8

78

78

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ma

Vira

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05C00205C00405C053 4

56

05C07905D04305D172Pl

asm

0123

0123

00 2 4 8

00 2 4 8

Wks post SIVmac316 i.v. ChallengeCourtesy of Phil Johnson, Children’s Hospital of Philadelphia

Solving the Problem of How to Control HIV Infection:Requires Two ElementsRequires Two Elements

• Robust Vaccine Platform1st generation- Non replicating vectors2nd generation Replicating vectors2nd generation- Replicating vectors

• Correct set of HIV antigens includedin the vaccine for induction of thein the vaccine for induction of the required cell mediated immune responses (CMI) to control HIVresponses (CMI) to control HIV

Recent Progress in Control of HIV/SIV Infections

Human Efficacy T i l

SIV- Monkey P t ti

CommentsTrials ProtectionAdeno-5 gag, pol, nef SIV-gag-pol-nef SIV-Monkey predicted

h ltNo Efficacy No Efficacy human results

gp120 SIV-gp 120 SIV-monkey predictedgp120No efficacy

SIV gp 120No efficacy

SIV monkey predicted human results

tNot Yet Tested Heterologous Adenovectors>2 log suppression

Improvement over 1st

generation Adeno

Not Yet Tested DNA + Adeno (whole proteome sans Env)>2 log suppression

Improvement over 1st

generation DNA+ Adg pp

Replicating Vector PortfolioNDV

HSV

C t t t

VEEVVSVCMV

CDVVEEV VSVReoSeVConstruct vectors

CDV Reo

CDVVEEV

In vitro expression, Stability screen

Small animal modelsNDV

Non-IAVINHP model

CMV

IAVI / Gates

IAVI / Academic VSV

MV

Attenuated VSV

Measles virusGSK / Crucell

Non IAVI

Primary candidate emerges

AcademicPartner

SeV IAVI / Biotech

VSV

Ad

Wyeth / Profectus

Adenovirus 5 / 7NCI

Clinical HSV

SeV Partnership

IAVI / Biotech

Vaccinia virus (Tiantan) National Center for AIDSBeijing

Pox

CandidatesHSV IAVI / Biotech Exploratory NYVAC-EuroVac

Determination of Which HIV Antigens are Required for Control of HIVfor Control of HIV

Immunogen Design will be faciliated by: • Clues from human “controllers” and from SIV

protection studies• New assay development: functional assays e.g. viral

inhibition assayPh I it ti d ti t i l t ti l CMI• Phase I iterative, adaptive trials testing novel CMI concepts for breadth, potency, durability, immunodominanceimmunodominance

• Screening Test of Concept (STOC) trials in developing world for preliminary assessments ofdeveloping world for preliminary assessments of efficacy

IAVI Network of Collaborative Sites:Vaccine Trials & Clinical Research

IAVI IndiaVaccine Trials & Clinical Research

Pune-NARI, India

Entebbe-MRC, Uganda Chennai-TRC, India

IAVI East Africa

Kangemi and KNH-KAVI, Kenya

Masaka MRC Uganda

Kilifi-CGMRC, Kenya

Masaka-MRC, Uganda

Kigali-PSF, RwandaKigali PSF, Rwanda

L k ZERHPMedunsa, South Africa

IAVI Southern Africa

Lusaka-ZERHP, Zambia

Cape Town-DTHC, S th Af i

Soweto, South AfricaSouth Africa

Vaccine Development Highlights: October 2008Clinical Research Milestones to Inform Vaccine Discovery &

Prepare for STOC Trials

Vaccine TrialsAdeno; Prime + Adeno; DNA + MVA

New candidates: BCG, Sendai, others

New Assay DevelopmentNew Assay DevelopmentViral Inhibition

Mucosal

Clinical Epidemiology StudiesIncidence

Reference Ranges

Acute Infection

Elite controllers

Training and AccreditationTraining and AccreditationLab and Clinic

Comprehensive Prevention Packagep g

• AIDS Vaccines must be seen as long-term tool to fight epidemic part ofAIDS Vaccines must be seen as long term tool to fight epidemic, part ofcomprehensive prevention package including:

Behavioral PreventionCare and TreatmentCircumcisionPre exposure prophylaxisPre-exposure prophylaxisSTI treatment including HSV2, HPV?MicrobicidesVaccines

• Even if one day AIDS vaccines are available, all efforts of classicalprevention must be sustained, strengthened and expandedp , g p

IAVI Gratefully Acknowledges our Multiple Partners andthe support of our Donorsthe support of our Donors