3 February 2020 (Geneva, Switzerland) – The Global HIV Vaccine Enterprise (the Enterprise), hosted by the International AIDS Society (IAS), shares the deep disappointment that the Phase 2b/3 HIV vaccine study HVTN 702 has been stopped by the trial sponsor, the National Institute of Allergy and Infectious Diseases (NIAID). The decision to halt the trial, conducted by the HIV Vaccine Trials Network (HVTN), follows the recommendation of the independent Data and Safety Monitoring Board (DSMB). Although the regimen did not prevent HIV infections, the DSMB did not express any concerns about safety.
The HIV vaccine research field had great hopes for this efficacy trial, which was conducted in South Africa - a country with one of the most severe HIV epidemics in the world. HVTN 702 tested a prime-boost regimen similar to the one which had shown modest efficacy in the RV144 trial conducted in Thailand and had been adapted to the type of HIV most common in southern Africa.
Linda-Gail Bekker, IAS Immediate Past President and Chair of the Enterprise Advisory Group said, “Whilst this is a significant setback for the field, we need to continue the quest for a preventive vaccine. The rates of HIV infection, which continue unabated in this region, should spur greater urgency, global attention and investment to the quest.”
The Enterprise applauds the HVTN for conducting an important study. “A well-conducted trial, even if efficacy is not observed, plays a critical role in informing HIV vaccine development,” said Roger Tatoud, Deputy Director of HIV Programmes and Advocacy at the IAS and who leads the work of the Enterprise. “We thank the trial volunteers, researchers and sponsors for their hard work and commitment. Other late-stage efficacy trials are continuing and these will be critical to add to our understanding of what an effective HIV vaccine strategy will be.”
Three other studies are currently being conducted investigating various prime-boost regimens. Janssen Vaccines & Prevention B.V. is testing a mosaic Ad26-mosaic / clade C gp140 envelop protein combination in the phase 2b HVTN 705/HPX2008 (Imbokodo) study in 2,600 adult women in South Africa and other sub-Saharan countries. A second efficacy trial of this regimen (modified to include a mosaic gp140) is being conducted in 3,800 cis-gender men and transgender individuals who have sex with cis-gender men and/or transgender individuals in the Phase 3 HVTN 706/HPX3002 (MOSAICO).”
HVTN 705 and 706 build on earlier clinical studies that demonstrated induction of immune responses associated with correlates of protection in non-human primate studies. HVTN 705 is expected to be completed in 2021 and HVTN 706 thereafter. A third vaccine efficacy trial, the Phase 2b PrEPVacc study employs an adaptive trial design to assess the combination of an HIV vaccine (DNA, MVA and gp140 envelop protein protein/adjuvant) and pre-exposure prophylaxis (PrEP) in sub-Saharan Africa.
In parallel with the ongoing active immunization vaccine studies, the Antibody Mediated Prevention (AMP) programme is testing passive antibody administration as a prevention strategy in the phase 2b HVTN 703/HPTN 081 and HVTN 704/HPTN 085 safety and efficacy trials. These are proof-of-concept trials in which the VRC01 broadly neutralizing monoclonal antibody (bNAb) is infused directly into participants every eight weeks. HVTN 703/HPTN 081 is testing the regimen in women in seven countries in sub-Saharan Africa while HVTN 704/HPTN 085 is being conducted with men who have sex with men and transgender people who have sex with men in the United States, Peru, Brazil and Switzerland.
“The effort, energy and resources that go into conducting trials of this size and complexity are extraordinary and the commitment of everyone involved is hugely appreciated. This level of passion, dedication and involvement will need to continue with renewed vigour as we move forward. We hope even more stakeholders will join the search for a preventive HIV vaccine,” said Anton Pozniak, IAS President.
Acting Communications Team Lead
About the Enterprise
Established in 2003, The Global HIV Vaccine Enterprise (the Enterprise), hosted by the International AIDS Society (IAS), unites stakeholders to share knowledge, foster collaboration, enable solutions, and expand support critical to the development of - and future access to - an HIV vaccine. The Enterprise at the IAS provides strategic and scientific advice on HIV vaccine research and development, and represents the views, interests and priorities of major stakeholders in the HIV vaccine field. The Enterprise is guided by the Enterprise Advisory Group (EAG) whose members are Linda-Gail Bekker, Susan Buchbinder, Larry Corey, Francois Dabis, Carl Dieffenbach, Mark Feinberg, Maureen Goodenow, Glenda Gray, Jerome Kim, Maureen Luba, Michael Makanga, Nina Russell, Johan Vekemans, and Robin Shattock. For more information, visit https://vaccineenterprise.org.
International AIDS Society
The International AIDS Society (IAS) leads collective action on every front of the global HIV response through its membership base, scientific authority and convening power. Founded in 1988, the IAS is the world’s largest association of HIV professionals, with members in more than 170 countries. Working with its members, the IAS advocates and drives urgent action to reduce the impact of HIV. The IAS is also the steward of the world’s most prestigious HIV conferences: the International AIDS Conference, the IAS Conference on HIV Science, and the HIV Research for Prevention Conference. For more information, visit www.iasociety.org.
About HVTN 702
The HVTN 702 study (Uhambo), conducted by NIAID-funded HIV Vaccine Trials Network (HVTN) enrolled 5,407 HIV-negative volunteers at 14 sites across South Africa.
The study population consisted of sexually active men and women aged 18 to 35 years randomly assigned to receive either the investigational vaccine regimen or placebo injections. The HVTN 702 vaccine regimen consists of two experimental vaccines: a canarypox-vector based vaccine called ALVAC-HIV (supplied by Sanofi Pasteur) and a two-component gp120 protein subunit (supplied by GSK) administered in an adjuvant to enhance the body’s immune response to the protein subunit. Both components have been modified from the versions used in RV144 to be specific to HIV subtype C, the predominant HIV subtype in southern Africa. Additionally, the protein subunit in HVTN 702 is combined with MF59, a different adjuvant than the one used in RV144, in the hope of generating a more robust immune response. Finally, the HVTN 702 vaccine regimen included additional booster shots in an effort to prolong the early protective effect observed in RV144.
Study participants received six injections over 18 months. The safety of HVTN 702 study participants was closely monitored throughout the trial, and participants were offered the local standard of care for preventing HIV, including access to oral pre-exposure prophylaxis (PrEP). The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is the sponsor of HVTN 702, which is co-funded by NIAID, the Bill & Melinda Gates Foundation (BMGF), and the South African Medical Research Council (SAMRC). Glenda Gray, M.B.B.C.H., F.C.Paed. (SA), is chair of the HVTN 702 protocol. The protocol co-chairs are Linda-Gail Bekker, M.D., Ph.D.; Fatima Laher, M.D.; and Mookho Malahleha, M.B.Ch.B., M.P.H.
For more information about the HVTN 702 study, please see the updated Questions and Answers. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.