EDCTP Third Forum
PARTNERSHIP AND AFRICAN LEADERSHIP IN VACCINE RESEARCH AND
HIV/AIDS DRUG MBOUP Souleymane
HIV VACCINE IN AFRICA• In 2005, 13 new trials of preventive AIDS vaccine
candidates began in 9 countries around the world. • Two of these involved vaccine candidates that
entered Phase II trials, an intermediate stage of clinical evaluation.
• Several of those newly initiated trials involved novel vaccination strategies
• Participation by Africa in those trials is continuously increasing with
• Rwanda started its first AIDS vaccine and South Africa began the country’s first Phase II AIDS vaccine trial
PROGRESS IN NUMBER OF COUNTRIES PARTICIPATING IN VACCINE TRIALS
2000 2006
1 country 8 countries participating in vaccine trials
CLINICAL TRIAL SITES IN AFRICA PARTICIPATING CLINICAL TRIAL SITES IN AFRICA PARTICIPATING IN HIV VACCINE TRIALSIN HIV VACCINE TRIALS
Cape Town, SA Durban, SASoweto, SA
Gabarone, BotswanaBlantyre, Malawi
KOSH,SA
Dar es Salaam, Tanzania
Entebbe, UgandaMasaka, Uganda
Kericho, KenyaKilifi, KenyaKisumu, Kenya
Kampala, Uganda
Nairobi, Kenya
Lusaka, Zambia Mbeya, Tanzania
Kigali, Rwanda
Medunsa,SA
Kayunga, UgandaMulago, Uganda
ActivePending
PROGRESS IN NUMBER OF COUNTRIES PARTICIPATING IN VACCINE TRIALS
2000 2006
Countries currently involved in vaccine trials
Countries preparing for vaccine trials
COMPLETED TRIALS IN AFRICA*COMPLETED TRIALS IN AFRICA*
*follow-up still ongoing
Phase Trial Name/ Sponsor
Country Status
ALVAC205 (Pasteur Merieux): Gag, pol, env (Subtype B)
Phase I(40)
DAIDS Uganda Complete
DNA Plasmid (Polyepitope Pharmexa – Epimmune): Polyepitope
Phase I (42) HVTN/DAIDS Botswana Complete
DNA MVA (Oxford / IAVI): Gag, polyepitope (Subtypes A)
Phase II (238) IAVI Kenya, Uganda, South Africa Complete
VEE Replicon (AlphaVax): Gag (Subtype C)Phase I (88) HVTN/DAIDS South Africa, Botswana Complete
Ad 5 (Merck): Gag (Subtype B)Phase II (120) HVTN/DAIDS South Africa, Malawi Complete
PREVENTIVE VACCINE CONCEPTSPREVENTIVE VACCINE CONCEPTSIN TRIAL IN AFRICAIN TRIAL IN AFRICA
Phase Trial Name/ Sponsor
Country Status
Adeno Associated (TG, IAVI): Gag-Pr-RT (Subtype C)
Phase II (90) IAVI Uganda, Zambia, South Africa Enrolling
DNA prime/ Ad5 boost (VRC): Gag, Pol, Nef, Env (Subtypes A,B,C)
Phase II (114) IAVI V001, VRC/DAIDS
Rwanda, Kenya Enrolling
Phase II (240) HVTN 204, VRC/ DAIDS
South Africa Enrolling
Phase II (324) RV172,WRAIR VRC/DAIDS
Uganda, Kenya, Tanzania Enrolling
PREVENTIVE VACCINE CONCEPTSPREVENTIVE VACCINE CONCEPTSIN TRIAL IN AFRICAIN TRIAL IN AFRICA
Phase Trial Name/ Sponsor
Country Status
Ad5 (Merck): Gag-Pol-Nef (Subtype B)
IIb (3000) HVTN503,Merck/DAIDS
South Africa Pending
DNA, MVA: Gag, RT, env, pol (Subtype A, E)II (60) SIIDC,
Karolinska, EU,Sida/SARE
C
Tanzania Pending
ALVAC-HIV vCP1521: Gag, Pro, Env (Subtype B, E)
I (50)Perinatal
HPTN027/DAIDS
Uganda Pending
FIRST “TEST OF CONCEPT TRIAL”IN AFRICA (Q4 2006):
MRKAd5 Trivalent Vaccine
ITRL ITRRgaghCMV
ψpA
MRKAd5 HIV-1 gag
ITRL ITRRpolhCMV
ψpA
MRKAd5 HIV-1 pol
ITRL ITRRnefhCMV
ψpA
ΔE1
MRKAd5 HIV-1 nef
1:1:1 mixing of 3 vectors
G. Gray, PHRU, SA
FIRST “TEST OF CONCEPT TRIAL”: HVTN 503
Will subtype B vaccine be efficacious against subtype C heterosexual infection
Markedly enhance the information on efficacy in women
Refine the assessment of the impact of pre-existing Ad5 titers
More than double the number of endpoints to enhance the evaluation of correlates of protection.
A South African Study to test subtype B vaccine (Ad5 gag, pol, nef) in subtype C region (similar to STEP HVTN502 in MSM in USA):
Adapted from G. Gray, PHRU, Soweto
VRC DNA PRIME RAD5 BOOST
Currently largest trial concept being tested in Africa
Enrolling into 3 trials /6 countries in Africa >600 participants
Involving 3 major vaccine initiatives /networks. – HIV Vaccine Trials Network (HVTN)– US Military HIV Research Program (USMHRP) – International AIDS Vaccine Initiative (IAVI)
PAVE 100 (in planning fo 2007/8) will be next proof of concept trial in Africa planning to enrol ~12,000 globally and ~8,000 in Africa
THERAPEUTIC VACCINE CONCEPTS THERAPEUTIC VACCINE CONCEPTS IN TRIAL IN AFRICAIN TRIAL IN AFRICA
Phase Sponsor Country Status
DNA Plasmid: Tat, rev, nef, gag, pol, env (Subtype B)
Phase II (60) FIT Biotech South Africa Enrolling
Tat Protein: (Subtypes B)
Phase II (60) AVIP /ISS South Africa Enrolling
E. Vardus, PHRU, SA
PLANNED VACCINE TRIALS
PAVE 100: DNA /Ad5; ~12 000 participants; 8 000 in Africa; multiple sites; multiple partners.
Mrk Ad5: Adolescent trial in SA (HVTN/DAIDS)
SAAVI DNA /MVA: Phase I trial in SA (SAAVI / HVTN /DAIDS)
EuroVac (NYVAC)
Chiron (Subtype C Env)
Tat Vaccine (AVIP /ISS)
50 volunteers1 country
20002000
400 volunteers8 countries15 trial sites
> 4 000 volunteers? 12 countries
20062006
INCREASING PARTICIPATION BY AFRICAINCREASING PARTICIPATION BY AFRICA
20082008
>10 000 volunteers
20102010
SCIENTIFIC CHALLENGES SPECIFIC TO AFRICA
Vaccine Pipeline is too narrow
Pre-existing immunity to vaccine vector
Genetic Diversity
Osmanov, pers. comm
« ARV therapy in sub saharan Africa : -Complicated combination regimens-Expensive and dangerous-Severe side effects-Rapid development of drug resistancein the community».
Instead of promoting expensive anddangerous ARV therapies…PREVENTION »
Lancet,1998
SHORT TERM EVALUATION ON SHORT TERM EVALUATION ON THE FIRST 175 PATIENTSTHE FIRST 175 PATIENTS
•• VirologicalVirological and and immunologicalimmunological resultsresults similarsimilarto Western countriesto Western countries
•• Excellent Excellent AdherenceAdherence
•• Good Good AccessibiltyAccessibilty and and AcceptabilityAcceptability
CLINICAL TRIALS IN AFRICA• Access to ARV for HIV-infected individuals in
resource-poor settings
• Efficacy ?
• Safety ?
• Adherence ?
• Potent, safe, inexpensive simplified regimen
R.LANDMAN1, R.SCHIEMANN1, S.THIAM2, A.CANESTRI1, M.VRAY4, C.DALBAN4 E. DELAPORTE3, S. MBOUP2, PS. SOW2, MA. FAYE NIANG2, PM. GUEYE2, G. PIEL4, G. PEYTAVIN 1, S. BADIANE2 , PM. GIRARD1, JP. COULAUD1, I. NDOYE2 , AIDS 2003
Once a day DDI/3TC/EFV regimen Once a day DDI/3TC/EFV regimen
in treatmentin treatment
naive HIVnaive HIV--1 infected adults in Senegal 1 infected adults in Senegal
ANRS 12ANRS 12--04 / IMEA 011 study (1999)04 / IMEA 011 study (1999)
-3,2-3,5 -3,5 -3,5
146 142184 199
0
-5
-4
-3
-2
-1
0
1
2
3
4
5
3 months 6 months 12 months 15 months
ΔVL log10 copies/m
l
-300
-200
-100
0
100
200
300
ΔC
D4 cells/m
m3
Evolution Evolution fromfrom baselinebaseline of viral of viral loadload and CD4 countand CD4 count
Once a day HAART regimen in treatment naive HIVOnce a day HAART regimen in treatment naive HIV--1 1 infected adults in Senegal infected adults in Senegal
ANRS 12ANRS 12--04 / IMEA 011 study04 / IMEA 011 study
HIV and non HIV pathologies 1212--04 / IMEA 01104 / IMEA 011
05
1015202530354045
J0 S2 M1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M11 M12
% Path VIH % Path non VIH
1. First trial in Africa of a simplified regimen
2. effective through treatment period among severely immuno-compromised individuals in resource-poor settings
3. ARV clinical trial in resource-poor settings feasible
4. Introduction et validation of new ARV Drug in SENEGAL
CLINICAL TRIALS in Africa
ONGOING TRIAL
• ANRS 1207/IMEA 025:
Once a dayTenofovir/Emtricitabine/Efavirenz
regimen (3 pills)
Viral loadANRS 1207/IMEA 025
-2,8-3,6
-3,6
-5-4-3-2-101
Série1 0 -2,8 -3,6 -3,6
JO (N=40) M1 (N=39) M3 (N=37) M6 (N=32)
Preliminary results : ANRS 1207/IMEA 025
• Good virological and immunological efficacy• Good adherence to treatment
• More simplified regimen
2 daily pillsTruvada (TDF/FTC)+EFV
1 daily pillTDF/FTC/EFV)
ATRIPLA® : TDF+FTC+EFV 1 daily pillATRIPLA® : TDF+FTC+EFV 1 daily pill
Mathias A., IAC 2006, Abs. TUPE0098
TRUVADA® SUSTIVA® ATRIPLA®+ =
ResearchResearch ClinicalClinical Center, Center, FannFann
HIV LABORATORIES AT LE DANTEC
HIV LABORATORIES AT LE DANTEC
CONCLUSION (1)
Increased African participation in vaccine trials
Increased funding to address scientific questions
Increased partnerships to accelerate the field
Increased success rate at an accelerated pace(Results of first IIb trials in Africa still 3 - 5 years)
CONCLUSION (2)
• ARV scaling up in developing countries• Host, viral,environmental factors (
logistical, operational etc..)• Affordable second line regimen required• Need of incresing African participation in
ARV clinical trials• Impact in developing and developed
countries
ACKNOWLEDGEMENTSACKNOWLEDGEMENTS
WILLIAMSON CDELAPORTE ESOW SALIF