1. HIV Vaccine Trials Network
Developing a Safe and Effective Vaccine for Prevention of HIV Infections Globally
State of Vaccine Research in Zimbabwe
Research reported in this publication was supported by the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under Award Number UM1A The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

2. Overview HIV Vaccine Science HVTN/Janssen collaboration
HIV Vaccine Trials Network
HIV Vaccine Research Trials in Zimbabwe
HVTN 107
HVTN 120
HVTN/Janssen collaboration
Background
HVTN 705/HPX2008

3. HIV Vaccine Trials Network
HIV Vaccine Science
HIV Vaccine Trials Network

4. Why an HIV vaccine?
February 6, 2014
“Ultimately, we believe, the only guarantee of a sustained end of the AIDS pandemic lies in a combination of non-vaccine prevention methods and the development of a safe and effective HIV vaccine”
11/6/2018

5. HIV Vaccine Trials Network
Established in 1999 to integrate the US and international efforts in testing HIV vaccines
Operant principle – public non-commercial funding was needed to effectively test candidate HIV vaccines
Global public health programs are the greatest beneficiary of an effective HIV vaccine
Main funding is by the NIH of the US government
Bill and Melinda Gates Foundation (BMGF) collaboration added in BMGF funds 50% of the clinical trial costs of HVTN efficacy trials

6. HVTN Mission
To fully characterize the safety, immunogenicity, and efficacy of HIV vaccine candidates with the goal of developing a safe, effective vaccine as rapidly as possible for prevention of HIV infections globally

7. Achieving HVTN’s Mission to Develop a Vaccine for the Prevention of HIV
Over 35 sites on 5 continents
All phases of clinical trials
Evaluating experimental vaccines for safety and immunogenicity
Testing vaccine efficacy
Over 65 clinical trials since 1999
11/6/2018

8. HIV Vaccine Science
RV144 – thai trial success

9. Thai Trial (RV144) Primary Results
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
Supachai Rerks-Ngarm, M.D., Punnee Pitisuttithum, M.D., D.T.M.H., Sorachai Nitayaphan, M.D., Ph.D., Jaranit Kaewkungwal, Ph.D., Joseph Chiu, M.D., Robert paris, M.D., Nakorn Premsri, M.D., Chawetsan Namwat, M.D., Mark de Souza, Ph.D., Elizabeth Adams, M.D., Michael Bebenson, M.D., Sanjay Gurunathan, M.D., Jim Tartaglia, Ph.D., John G. McNeil, M.D., Donald P. Francis, M.D., D.Sc., Donald Stablein, Ph.D., Deborah L. Birx, M.D., Supamit Chunsuttiwat, M.D., Chirasak Khamboonruang, M.D., Prasert Thongcharoen, M.D., Ph.D., Merlin L. Robb, M.D., Nelson L. Michael, M.D., Ph.D., Prayara Kunasol, M.D., and Jerome Kim, M.D., for the MOPH-TAVEG Investigators*
An HIV vaccine that prevents acquisition is possible
What about in Africa?
0.5
1.0
1.5
3.5
0.9
0.8
0.7
0.6
0.4
0.3
0.2
0.1
0.0
Years
Probability of HIV Infection (%)
2.0
2.5
3.0
Placebo
Vaccine
Modified Intention-to-Treat Analysis*
Vaccine regimen had 60% efficacy at 12 months, but came down
to 31.2% efficacy at 3 years after vaccination

10. Questions for Africa
Will the same vaccine used in RV144 work just as well in the African population?
Will a vaccine engineered for subtype C work well?
Can we improve how well it works by adding adjuvants and changing the dosing regimen?
HVTN 100
HVTN 702
HVTN 107
HVTN 120

11. Preventive Vaccine Development
Well HIV-uninfected adults randomized
Primary Objective
Assess Vaccine Efficacy to prevent pathogen-specific disease
(does it work?)
Secondary Objective
Assess vaccine-induced immune responses as “correlates of protection”
(what is it that makes it work?)
Vaccine
Placebo
Receive
inoculations
Measure immune response
Follow for new HIV infection

12. 2 HIV vaccine efficacy trials in 2017
Building on RV 144: ALVAC & gp120/MF59
South Africa
HVTN 702
Efficacy Studies
Multi-clade approach: Ad26 Mosaic & Clade C gp140
South Africa, Malawi, Mozambique, Zambia, Zimbabwe
HVTN 705

13. 2 HIV correlates of protection trials in 2017
Adjuvants: ALVAC & gp120/MF59 vs Alum
Mozambique, South Africa, Zimbabwe (28/132)
HVTN 107
Correlates Studies
Adjuvants and dose: ALVAC & gp120/MF59 vs ASO1B
South Africa, Tanzania, Zambia, Zimbabwe (28/320)
HVTN 120

14. Janssen Vaccines and Prevention – HIV Vaccine Program
background

15. Pre-clinical and clinical experience
The vaccine candidates are very effective in preventing HIV infection in NHP models
Protection was confirmed in several studies
Protection was correlated with antibodies to HIV envelope as well as with the T-cell responses to the vaccines
Phase I (clinical) studies showed that humans can make the same type and levels of antibodies achieved by NHP

16. Safety studies have been performed in about 650 participants
HVTN 705/HPX2008 products
Safety studies have been performed in about 650 participants
Product
# of vacinees
Ad26.Mos.HIV
(very similar to Ad26.Mos4.HIV)
~350
Ad26.Mos4.HIV
~115 (~235 by the time HVTN 705 will start)
Clade C gp140
~450 (~575 by the time HVTN 705 will start)
In multiple studies, these vaccines have been well tolerated
and have not raised any safety concerns

17. Go/No Go criteria met for HVTN 705
Endpoint
Target
(LL of 95% CI)
Phase I
Wk28 results
Humoral
IgG binding responses on clade C Env
ADCP responses to Clade C Env
Cellular
ELISpot responses to at least one ENV peptide pool
Env boost
IgG to clade C Env of Ad/Ad+Env over Ad/Ad
Magnitude
>2.15 log10 cPTE Env ELISpot OR
>3.8 log10 C97 ELISA
Subjects should be above BOTH response thresholds
Confidential –
Do not disclose

18. Clade C gp140 (250 mcg + adjuvant)
Schema
Group N
Month 0
Month 3
Month 6
Month 12 1
1300
Ad26.Mos4.HIV +
Clade C gp140 (250 mcg + adjuvant) 2
Placebo
Total: 2600 female participants
Anticipated enrollment: 14 months
Anticipated total study duration: 50 months (includes enrollment and follow-up)

19. Standard of prevention
All participants will be offered comprehensive prevention methods:
Risk reduction counselling
Condom provision
PrEP referral where available
PEP access
Couple counselling
STI treatment provision
Contraception
The trial will compare the vaccine + Standard of Care vs. Standard of Care alone

21. Summary Test of Concept Trial:
Trial to see if the vaccine can work in the most vulnerable subjects of people at risk – women in sub-Saharan Africa
If this trial shows that the vaccine is efficacious, future trials including men in all of the world will follow
Trial is co-funded by the US National Institutes of Health and the Bill and Melinda Gates Foundation

22. Thank You!