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

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

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

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) 11/14/2018

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 11/14/2018

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. 11/14/2018

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 11/14/2018

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 11/14/2018

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

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 11/14/2018

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.

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.

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 11/14/2018

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. 11/14/2018