HIV Vaccine Clinical Trials at CIDRZ Developing a Safe and Effective Vaccine for Prevention of HIV Infections Globally Christine Namakobo Senior Research Nurse Matero Clinical Research Site
State of Global HIV Epidemic (2016) Estimated 36.7 million people living with HIV HIV has killed more than 34 million to date 1.8 million people were newly-infected Sub-Saharan region bears disproportionate burden with 70% of global infections and only 6 % of the world s population
Zambia (2016) 1.2 million (12.9%) living with HIV 60,000 new Infections including 5,000 in children 85,000 children currently living with HIV, of which 20,000 died due to AIDS in 2016 65% of HIV infected adults are on ART
Is HIV Prevention Working? Prevention of HIV transmission is the long term global solution for the HIV pandemic Current interventions include: Testing and counseling for HIV and STIs Education and behaviour modification Use of male and female condoms Voluntary male circumcision Pre- or post-exposure prophylaxis (PrEP, PEP) Interruption of transmission from mother to child Topical microbicides Protection by these interventions is limited by: Need for long-term continuous adherence Continuous uninterrupted access to products Sustainable funding 11/22/2017 4
Universal Access to Effective Antiretroviral HIV Therapy (ART) Significant progress toward this goal has been achieved, but in many regions of sub-saharan Africa limited access undermines the prevention potential of ART Many millions of people still do not receive treatment The costs and healthcare burden of delivering everincreasing amounts of treatment in resourceconstrained settings pose significant challenges 11/22/2017 5
Progress Towards the 90 90 90 Target, Eastern and Southern Africa, 2015 1 2015 measure derived from data reported by 12 countries, which accounted for 77% of people living with HIV in the region. 2 2015 measure derived from data reported by 8 countries. Regionally, 14% of all people on antiretroviral therapy were reported to have received a viral load test during the reporting period. Source: UNAIDS special analysis, 2016; for more details, see annex on methods. 11/22/2017 6
HIV Epidemic Continues Even in countries with longstanding ART the epidemic continues Under status quo, 49 million new infections predicted worldwide 2015-2035 (Medlock et al., PNAS, 2017) 11/22/2017 7
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 8
Why a Vaccine? Vaccination is among the safest and most effective medical interventions available for infectious diseases Vaccination does not require sustained and continuous adherence to be effective A vaccine able to prevent HIV infection would have a significant impact on the health, social and economic burden of HIV/AIDS 11/22/2017 9
Why a Vaccine? Recent modelling study showed that introducing a partially effective (30%) with limited coverage in Southern Africa could result in an significant reduction in HIV incidence compared to a nonvaccine scenario 11/22/2017 10
Potential Impact of a Vaccine New Adult Infections in Low- and Middle- Income Countries by Year and Vaccine Scenario Total new infections averted by an AIDS vaccine between 2015-2030 30% efficacy, 20% coverage 5.5 million 50% efficacy, 30% coverage 17 million 70% efficacy, 40% coverage 28 million Even a vaccine with low efficacy and limited coverage can impact the epidemic and play a role in preventing future infections Stover J, et al. The impact of an AIDS Vaccine in Developing Countries: A New Model and Initial Results. Health Affairs 26(4):1147-1158 (2007) 11/22/2017 11
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 11/22/2017 12
HIV Vaccine Trials Network (HVTN) Global network of clinical trial sites
Preventive Vaccine Development: study design Randomize Receive inoculations Measure immune response Vaccine Placebo Study phases Early Phase Human Studies: Assess safety, tolerability & immunogenicity Late Phase Human Studies: Assess Vaccine Efficacy to prevent disease Follow for clinical endpoint (pathogen-specific disease) 11/22/2017 14
Pipeline of Vaccine Studies for sub-saharan Africa (blue=zambian sites) HVTN 100: Phase 1 study to evaluate safety and immunogenicity profiles of an ALVAC-HIV (vcp2438) prime and bivalent subtype C gp120/mf59 boost vaccine in South African adults HVTN 111: Phase 1 study to evaluate safety and immunogenicity profiles of a DNA prime and bivalent subtype C gp120/mf59 boost in South African adults HVTN 107: Phase 1 study to compare safety and immunogenicity profiles between two different boost components after an ALVAC-HIV (vcp2438) prime, either bivalent subtype C gp120/alum or bivalent subtype C gp120/mf59 HVTN 113: Phase 1/2 study to evaluate two prime regimens (DNA or ALVAC) and two bivalent subtype C gp120 boost (i.e., either with MF5 or AS01B) HVTN 120: Phase 1/2a clinical trial to evaluate the safety and immunogenicity of ALVAC-HIV (vcp2438) and of MF59 - or AS01 B -adjuvanted clade C Env protein, in healthy, HIV-uninfected adult participants HVTN 108: Phase 1 study to evaluate safety and immunogenicity profiles of a DNA prime and either bivalent subtype C gp120/mf59 or bivalent subtype C gp120/as01b boost HVTN 702: Phase 2B, placebo-controlled efficacy study intended to demonstrate the efficacy of the ALVAC-HIV (vcp2438) prime and bivalent subtype C gp120/mf59 boost in adults in the RSA HVTN 705: /VAC89220HPX: Phase 2b efficacy study of a heterologous prime/boost vaccine regimen of Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140 in preventing HIV-1 infection in women in sub-saharan Africa 11/22/2017 15
HVTN 111 A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV clade C DNA and of MF59- adjuvanted clade C Env protein, in healthy, HIVuninfected adult participants
HVTN 111 Primary Objectives: Safety and tolerability & Immunogenicity Sites: Malawi, South Africa, Tanzania, Zambia Participants: 132 healthy, HIV-uninfected participants, 18-40 Current status: 28 enrolled, completion by July 2018
HVTN 120 A phase 1/2a clinical trial to evaluate the safety and immunogenicity of ALVAC-HIV (vcp2438) and of MF59 - or AS01 B -adjuvanted clade C Env protein, in healthy, HIV-uninfected adult participants
HVTN 120 Primary Objectives: Safety and tolerability & Immunogenicity Sites: South Africa, Tanzania, Zambia, Zimbabwe Participants: 320 healthy, HIV uninfected participants, 18-40 Current status: Enrollment to start Nov 20, 2017
HVTN 705 A multicenter, randomized, double-blind, placebocontrolled phase 2b efficacy study of a heterologous prime/boost vaccine regimen of Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140 in preventing HIV-1 infection in women in sub-saharan Africa
2 HIV vaccine efficacy trials in 2017 Efficacy Studies South Africa HVTN 702 Malawi, Mozambique, South Africa, Zambia, Zimbabwe HVTN 705 11/22/2017 21
HVTN 705: Objectives To evaluate vaccine efficacy in preventing HIV infection in women residing in sub-saharan Africa To evaluate the safety and tolerability
Why Women?
HVTN 705: Summary Test of Concept Trial: To see if the vaccine can work in the most vulnerable subjects of people at risk > women in sub-saharan Africa Not a licensure trial Trial is co-funded by the U.S. National Institutes of Health and the Bill & Melinda Gates Foundation 25
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HVTN 705: Design Group N Month 0 Month 3 Month 6 Month 12 1 1300 Ad26.Mos4.HIV Ad26.Mos4.HIV Ad26.Mos4.HIV + Clade C gp140 (250 mcg + adjuvant) Ad26.Mos4.HIV + Clade C gp140 (250 mcg + adjuvant) 2 1300 Placebo Placebo Placebo + Placebo Placebo + Placebo Total: 2600 female participants: CIDRZ 165 Enrollment: 14 months Study duration: 50 months 26
HVTN 705 If this trial shows that the vaccine is efficacious, future trials, including men, will follow Start date Oct 31, 2017
Summary The number of new global HIV infections has plateaued despite implementation of multiple preventive tools 2020 target for reduction in new HIV infections cannot be met The development of a vaccine with moderate efficacy and coverage has the potential to significantly reduce the number of new infections CIDRZ is part of a global HIV vaccine effort and has a pipeline of 3 studies which we are currently working on
Thank You! 11/22/2017 29