Investigational HIV vaccine fails
The National Institute of Allergy and Infectious Diseases (NIAID) recently made the decision to terminate the phase IIb/III HVTN 702 (Uhambo) trial that was investigating a vaccine to prevent HIV.
“An HIV vaccine is essential to end the global pandemic, and we hoped this vaccine candidate would work. Regrettably, it does not,” said NIAID director Dr Anthony Fauci. “Research continues on other approaches to a safe and effective HIV vaccine, which I still believe can be achieved.”
The HVTN 702 trial, initiated in 2016 in South Africa, aimed to test a vaccine regimen that was developed based on the only vaccine regimen that had previously shown evidence of efficacy in preventing HIV. The previously tested regimen was assessed in the RV144 trial, which was conducted in Thailand. For the HVTN 702 trial, the vaccine regimen was modified to be specific to the Clade C subtype of HIV, which is the most common type in South Africa.
Participants in the HVTN 702 trial were 5,407 sexually active, HIV-negative individuals aged 18–35 years from South Africa. They were randomized 1:1 to receive intramuscular injections of ALVAC-HIV* (vCP2438) at months 0 and 1, and an injection of ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59** at months 3, 6, and 12, or placebo at months 0, 1, 3, 6, and 12. [https://clinicaltrials.gov/ct2/show/NCT02968849, accessed 19 March 2020] Participants were also given access to daily oral pre-exposure prophylaxis (PrEP) and local standard of care prevention strategies including counselling on behaviour to reduce HIV risk, and information and referral for treatment of sexually transmitted infections, male circumcision, and antiretroviral therapy.
Interim analysis was conducted in January 2020 by an independent data and safety monitoring board (DSMB) based on the data of 2,694 and 2,689 vaccine and placebo recipients, respectively. HIV infection was detected in 129 vaccine recipients and 123 placebo recipients.
Based on these findings, the DSMB recommended cessation of vaccination administration, due to the lack of efficacy of the vaccine regimen. However, they noted that there was no increase or decrease in HIV infection rates, and that the study was not stopped due to safety issues.
While patients are no longer receiving vaccinations, follow-up is ongoing, with patients having continued access to PrEP, as well as counselling, testing, and safety monitoring. [AIDS Vaccine Advocacy Coalition (AVAC), available at https://www.avac.org/trial/hvtn-702; https://www.hvtn.org/, accessed 19 March 2020]
“The people of South Africa have made history by answering this important scientific question. Sadly, we wish the answer was different,” said trial protocol chair Professor Glenda Gray, President and CEO of the South African Medical Research Council, Cape Town, South Africa.
“We will continue to explore promising avenues for preventing HIV with other vaccines and tools, both in South Africa and around the world,” she added.
Disappointment reverberates through the community
The impact of the findings and subsequent decision to cease vaccinations was felt throughout the HIV/AIDS research and support community.
“While we are obviously disappointed with the results, important science has been learned that can be carried forward to future trials. I thank the study team for this important vaccine trial,” said Winnie Byanyima, executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), in a press release.
“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,” noted Linda-Gail Bekker, immediate past president of the International AIDS Society and chair of the Global HIV Vaccine Enterprise Advisory Group, in a press release.
“We always hope that efficacy trials will show positive results that lead to new prevention options,” said Mitchell Warren, executive director of AVAC, in a press release. “It is very disappointing that this vaccine candidate does not work, but the trial was well-conducted and got an answer as quickly as possible.”
“A vaccine is absolutely essential to achieving a durable end to the HIV epidemic,” he continued. “It will be important for the HVTN 702 partners to share data from the study as quickly as possible, and for the field to come together as it did after RV144 to ensure that what can be learned from this trial is fed back into the research pipeline expeditiously,” he added.