1. Annual Research Day 17 April 2015
HVTN 107
A Zimbabwe Update
Dr Portia Hunidzarira
Annual Research Day 17 April 2015

2. Presentation outline Background HVTN 107 study design
Preparatory work in Zimbabwe for HVTN 107
Current status for study initiation
11/14/2018

3. Background
HIV vaccine research worldwide has been ongoing for about 30 years.
Since 1985, more than 30 vaccine candidates have been tested in 80 clinical trials. Only 4 of these have proceeded to efficacy trials.
There is still no licensed vaccine against HIV.
RV144 Thai trial was the first ever large scale vaccine study to show that a HIV vaccine can actually work.
HVTN 107 will be the first HIV vaccine trial in Zimbabwe.
With this in mind HVTN has embarked on a series of studies in Southern Africa to build on the success of the RVI44.. With this in mind HVTN

4. HVTN 107 Study design
Phase 1/2a,multicenter, double blind, randomised trial.
132 participants in total across 3 countries Mozambique, Zimbabwe & South Africa.
Zimbabwe will enroll 26 participants (about 20% of the total)
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5. Vaccine candidate
The 2-Vaccine combination used in the RV144 trial has been modified to match HIV subtype C found in Southern African region.
2 HIV vaccines
Prime: ALVAC-HIV (vCP2438) pox
Boost: Bivalent Subtype C gp120 protein
2 adjuvants
MF59®
Aluminium hydroxide
We know that HIV-1 has many sub-types. These subtype are geographically distributed. Type C is predominantly found in Southern Africa and type B &E in Thailand.
The prime boost regimen will be used with a pox-protein vaccine.
In addition to further optimize this regimen adjuvants have been added, MF59 & aluminum hydroxide.
MF59® has been successfully used in vaccines against influenza, hepatitis B and HIV
Aluminum hydroxide used in measles vaccines
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6. Vaccine description
ALVAC-HIV (vCP2438) is a man-made weakened canarypox virus vector carrying genes copied from HIV-1 to safely deliver them to the body’s immune cells.
Bivalent Subtype C gp120 is a lab-made protein with 2 subunits copied to look like the subtype C HIV Env surface glycoproteins.
Adjuvants are products used to boost the body’s reaction to the vaccine.
Alum adjuvant has been used for years in vaccines like Diphtheria, pertussis, tetanus and anthrax
MF59® is a newer adjuvant and is being used in licensed vaccines for flu & hepatitis B
A weakened carnary pox vector is like a delivery truck carries goods to a store for use. Genes carried are expressing HIV-1 env gp120 (clade C), env gp41 TM (clade B), gag (clade B), and protease (clade B) coding sequences.
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7. Main objectives of study
To compare the humoral immune responses induced by the MF59®- and alum-adjuvanted vaccine regimens
To evaluate the safety and tolerability of each vaccine regimen
To further evaluate the humoral and cellular systemic immune responses to the different vaccine regimens
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8. Eligibility for study Male and female adults aged 18-40yrs
Low risk for HIV infection
HIV negative
General good health shown by medical history, physical exam and screening laboratory tests.
Willing to give an informed consent
Women not pregnant/breastfeeding & on a reliable contraceptive
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9. 12-month vaccination schedule
HVTN 107 Vaccination schedule
Additional prime boost given at 12 months unlike the RV144 regimen 1 3 6 12 18 24 30 36
Participants will be followed up over 3 years but will only have 19 scheduled clinic visits . In 12 months they will receive a 5 vaccinations, 3 of which will have a booster. The booster will have added adjuvants either MF59/Alum. This regimen differs from the RV144 study in that there is an extra prime boost injection at month 12 where the RV144 efficacy began to wane off. Follow-up will be done for immunogenicity, safety and tolerability.
ALVAC-HIV (vCP2438) priming
12-month vaccination schedule
Bivalent Subtype C gp120
boosting + adjuvants

10. Vaccine-induced seropositivity (VISP).
Experimental HIV vaccines may induce Ab production to HIV antigens, producing reactive results on commercially available HIV test kits.
Volunteers who develop VISP will be registered and followed for specialised HIV testing by the HVTN laboratory.
Common side effects expected of vaccines include
Malaise/fatigue, myalgia, arthralgia, nausea/vomiting, lymphadenopathy, asthenia, fever, or headache in the first few days following injection, Arm movement limitation,Severe injection site pain or tenderness
·Chills, flu-like syndrome, diarrhea, rash, or dizziness in the first few days following injection
Varying hypersensitivity reactions
VISP it has the side effect with most likely to have social impact on participants
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11. Stakeholder Engagement
Community Advisory Board
Chitungwiza HS
Regulators Bodies
Training
Pre-submission discussions
Ministry of Health and Child Care
Epidemiology and Disease Control
AIDS and TB Unit
Permanent Secretary for Health
Minister of Health and Child Care
Since Seke South site was chosen as an HVTN CRS in April 2014 the following steps have begun to make the site ready to conduct trials. Key stakeholders have been engaged from the community and policy makers and regulatory bodies.

12. Seke South CRS Renovations
The site has been renovated to increase its capacity to conduct a vaccine trial of this kind. Highly specialised equipment has been purchased for pharmacy where the vaccines are stored and prepared for administration. A higher voltage generator has been installed to provide a uninterrupted energy supply to the equipment.

13. Start date of HVTN107
The protocol team are working to revise the HVTN 107 protocol and it should be released to us later this month
Regulatory submissions and reviews underway
Study vaccines available from manufacturers from August 2015
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14. I wish to acknowledge all our partners the community, the CAB, all regulatory bodies and the ministry of Health and child care. I leave you with this this statement of what an HIV vaccine means to us all.
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