PrEPVacc HIV trials’ results ‘surprising’ as dummy group clocks less infections

HQ Team

July 24, 2024: HIV vaccine trials conducted in Eastern and Southern Africa threw up surprising results when more infections were reported in the two vaccine groups than in the placebo or dummy group.

PrEPVacc, an African-led, European-supported HIV prevention project, recruited over 1,500 people aged between 18 and 40 at four trial sites in Uganda, Tanzania, and South Africa.

PrEPVacc tested two different combinations of HIV vaccines and compared each to a placebo — in this case saline water. One regimen combined a DNA vaccine with a protein vaccine, and the second combined the same DNA vaccine and another protein-based vaccine.

It was the first time that a trial evaluated HIV vaccines and pre-exposure prophylaxis (PrEP) at the same time. 

In November 2023,  PrEPVacc’s independent data monitoring committee decided to stop the vaccination component of the study. However, it allowed the oral PrEP component to be completed.

Only vaccine efficacy trial

At the time of the IDMC recommendation in November 2023, PrEPVacc was the only remaining active HIV vaccine efficacy trial in the world. 

The participants had four vaccine injections, three over approximately six months and a fourth a year after enrolment. The trial ran from 2020 to 2024.

In the primary vaccine analysis, of those who received at least three injections of the first combination regime, 11 out of 532 participants acquired HIV, an incidence rate of 1.73 infections per 100 person-years.

That compared to three out of 523 participants who received the placebo, an incidence rate of 0.48 infections per 100 person-years.

‘What does this mean?’

The vaccine trial results, announced on July 23 at AIDS 2024 in Munich, Germany, reported more infections in the two vaccine arms.

In the second vaccine combination analysis, nine out of 244 participants acquired HIV,  compared to two out of 251 participants who received the placebo.

The researchers said they could draw a definitive conclusion about “what this means” because the statistical ‘confidence intervals’ for the comparison are so wide, indicating a high degree of uncertainty.

“The investigators cannot immediately explain the relatively low incidence of HIV in the placebo arm. They have ruled out statistical errors and differences in self-reported PrEP adherence use of condoms, and risk behaviours between the groups,” according to a statement from PrEpVacc. 

Professor Sheena McCormack, PrEPVacc Project Lead based at the Medical Research Council clinical trials unit at University College London, UK, said:  “You always go into a trial with a question to answer and an open mind, but seeing the imbalance between infections in the vaccine groups and the placebo was a surprise and one that we cannot explain. 

“We suspect chance but cannot rule out the possibility the result is plausible, so it is clear we need to continue to support the participants and provide HIV testing to monitor the trend.”

PrEP oral vaccine

PrEPVacc’s Trial Director, Dr Eugene Ruzagria, who presented the results said: “We stopped the vaccine trials in November 2023 as soon as we had evidence that the vaccines could not be shown to be effective.”

PrEPVacc’s oral PrEP results are separate from the vaccine results and will be announced later in 2024.

The trials were conducted by 80 senior scientists, clinicians, social scientists, community liaison specialists and professional support roles, from 15 partner organisations. 

They have extensive experience working with HIV and other infectious diseases, as well as clinical trials, specifically in carrying out HIV vaccine and PrEP trials across Europe and sub-Saharan Africa, according to the PrEPVacc statement.