One of the biggest HIV vaccine trials in the world, the HVTN 702 study, was stopped late on Monday because the vaccine had not been proven effective in preventing HIV. This is according to the United States National Institute of Allergy and Infectious Diseases (NIAID), who are one of the funders of the clinical trial.
The HVTN 702 study, also known as the Uhambo trial, was launched in South Africa in 2016 to test whether an experimental vaccine regimen could safely prevent HIV infection among adults in South Africa.
International HIV advocacy organisation AVAC states that the trial was stopped following a scheduled review by an independent data safety monitoring board (DSMB) that showed no significant difference between the vaccine and placebo arms of the trial. The data safety monitoring board also identified no safety concerns.
Mitchell Warren, executive director of AVAC, explains that efficacy studies are always looking at both efficacy and safety of an intervention.
“The good news for this trial is that while it has stopped early for non-efficacy, the vaccines were safe. The role of the DSMB is to review the data at regular intervals and stop a trial if there are any signals from the data that the product is not working, as in this study, or for any indication that the product might be unsafe. There were no safety concerns related to HVTN 702,” Warren tells to Health-e News.
According to NIAID, 129 HIV infections occurred among the vaccine recipients, and 123 HIV infections occurred among those that received the placebo.
This, however, doesn’t mean the non-efficacy of the vaccine caused the HIV infections.
“The vaccines used in this study are not made from live HIV, killed HIV, parts taken from HIV, or HIV-infected human cells. The HIV vaccines being tested are made from synthetic (man-made) copies of HIV pieces. Therefore, the vaccines cannot cause HIV infection or AIDS,” the Uhambo website explains.
Amongst a pool of about 5 400 volunteers, Warren tells Health-e News that the number of infections that occurred during the trial are statistically the same.
“That means the risk for acquiring HIV was no different whether a participant received the vaccine or the placebo, and the vaccine is, therefore, not effective.”
Whilst this might pose questions about the future of HIV trials in Africa, a statement released by AVAC explains that “the vaccine approach in HVTN 702 is different from that being tested in other large scale vaccine efficacy studies.” The other large scale trials AVAC refers to are HVTN 705/ HPX2008, known as the Imbokodo study, and HVTN 706/HPX3002, or the Mosaico study.
The statement continues: “It is also different from the planned PrEPVacc Study, which will test yet another vaccine strategy along with oral PrEP. Stopping the HVTN 702 study does not affect these trials or any other HIV prevention efficacy trials taking place globally.”
Prior to calling off the trial, Warren says that part of the trial’s protocol included scheduled reviews. Those reviews didn’t raise any safety issues, but also didn’t have enough data for the DSMB to decide about non-efficacy — until now.
Disappointed but still determined
South African-based HIV organisation Advocacy for Prevention of HIV and Aids (APHA) says it is disappointing that the trial couldn’t reach its planned ending of 2021, but that it’s encouraged by the integrity of the trial. To APHA, the manner in which the trial was conducted shows that volunteer’s safety was placed first, and a decisive action to stop it when an independent review showed that the vaccine doesn’t have the potential to prevent HIV.
“It shows trials are conducted in the most ethical and human rights orientated environment,” Ntando Yola of APHA tells Health-e.
Although HVTN 702 was only conducted in South Africa, the Imbokodo study is conducted in other parts of Africa, and according to Yola, this provides even more opportunity to engage closely with communities.
“Mobilise with measured hope to see what the outcome will be for this other vaccine study and other HIV prevention studies that are most needed to provide additional tools for HIV prevention in our region,” he says.
Tian Johnson, of The Vaccine Advocacy Resource Group (VARG), says even though he’s disappointed, he doesn’t regard HVTN 702 as a failed trial. Based on the data, he urges researchers and advocates to now work more closely than ever before to ensure research is truly community-owned and that the science behind HIV vaccines is compatible with the lived realities of communities.
“You can have the most effective vaccine in the world but if communities don’t know about it, if communities are unable to access it and receive quality counselling and support, especially in South Africa where the vast majority of trial participants are black and live in one of the most unequal countries in the world, amidst a failing health care system, the millions of dollars of investment will come to nothing,” Johnson says.
He adds that “every trial teaches us something, every trial generates data that can be used to advance our progress towards an effective, safe, affordable and accessible vaccine.”
“If anything, this news means that the many other trials underway and coming up will be more robust and leverage off the wealth of data from 702 and trials like it.”
Continued vaccine support needed
According to AVAC, trial teams at each site are currently calling participants back to site, explaining how the trial stopped and what it means to them. While the participants will not get any more injections, they remain in the study for follow-up consultations, including HIV counselling, testing and safety monitoring. The researchers will also examine information generated by the trial to inform ongoing and future vaccine research.
Then, there will be a number of community meetings to help participants and their communities understand what happened. HIV prevention advocates in South Africa will also hold meetings and work with the broader community to understand this result, as well as the need for continued support for vaccines and other HIV prevention research. APHA and VARG are co-hosting a webinar about what the discontinuation of the HVTN 702 trial means for HIV prevention research in Africa.
Warren says it’s important for vaccine research to continue, in conjunction with scale-up access to current treatment and prevention options.
Currently, it’s too soon to know what made the regimen fail in South Africa but NIAID explains that, in order to test the RV144 vaccine concept outside of Thailand, several changes had to be made to the vaccine regimen. The vaccine was tailored to the South African environment, as it tackled the type of HIV most common in the country, termed Clade C.
Scientists changed three different aspects of the RV 144 vaccine to adapt and improve it for South Africa. The immune responses elicited by the RV 144 and HVTN 702 vaccine regimens were examined and found to be comparable.
Activists and experts believe that as scientists continue to analyse data from HVTN 702, their findings will no doubt prove invaluable to both why the vaccine trial failed, and how to create more efficient HIV prevention measures. – Health-e News