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
Loa
d (
0 2 4 8 0 2 4 8
78
78
5L7 N4
ma
Vira
l
456
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
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