In July 2024 PrEPVacc, an African-led, European-supported HIV prevention study, announced that the results of the HIV vaccine trial in Eastern and Southern Africa “conclusively” show that neither of two experimental vaccine regimens tested reduced HIV infections among the study population. This announcement follows the December 2023 update that vaccinations in the trial had been stopped in response to an independent assessment that there was “little or no chance” of efficacy against HIV acquisition. Although the results report more infections in the vaccine arms than in the placebo arms, the researchers are not drawing a definitive conclusion from this because the statistical confidence intervals for the comparison are too wide.
The importance of the trial
In the countries where the trial was conducted, South Africa, Tanzania, and Uganda, it is estimated that a total of 10.7 million people were living with HIV in 2022, and 244,000 adults and children were newly diagnosed with HIV. PrEPVacc was the only ongoing HIV vaccine efficacy trial at the time its participants exited the study and is the first HIV vaccine efficacy trial conducted in East African countries.
The trial tested two combinations of HIV vaccines and compared these to a placebo (saline water) in a 1:1:1 randomisation. One regimen combined a DNA vaccine (DNA-HIV-PT123) with a protein vaccine (AIDSVAX B/E). The other combined the same DNA vaccine with a modified non dividing virus vector (MVA-CDMR) and a protein-based vaccine (CN54gp140).
No protective effect
In the primary vaccine analysis, it emerged that neither vaccine combination offered a protective effect. Not only were HIV incidence rates higher in the vaccine arms, but the matched placebo groups were “much lower than expected by the investigators”, adding to “uncertainty”.
Expert reactions
Trial Director, Dr Eugene Ruzagira from the MRC/UVRI and LSHTM Uganda Research Unit in Uganda, presented the results of the trial to the AIDS 2024 conference and commented on the “exemplary” dedication of participants.
“They and their communities should be very proud of their efforts and their important contributions to the global effort to prevent HIV.”
Although the trial results might seem disappointing, there is “positive news”:
“Repeated risk reduction counselling and use of proven HIV prevention tools helps people navigate their risks better. The number of new infections has fallen throughout the six years we have been monitoring the HIV incidence in each study community.”
Dr Ruzagira is “proud of the efforts we have made” and looks forward to the findings from PrEPVacc’s integrated social science research and the results of the PrEP study later in the year. Professor Sheena McCormak, Project Lead at the Medical Research Council clinical trials unit at UCL, acknowledged the “surprise” of finding an “imbalance” between vaccine group infections and placebo group infections.
“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.”
Chief Investigator, Professor Pontiano Kaleebu of the MRC/UVRI & LSHTM Uganda Research Unit in Uganda, reflected that the vaccine questions from the trial “have been answered” and the vaccines “won’t be taken further”. However, the results will be investigated and used to inform future vaccine design.
“The results have been surprising, and they have been disappointing. But that is science.”
Professor Kaleebu remains focused on developing “choices” for the HIV prevention “toolbox”.
“A vaccine against HIV remains a critically sought and important part of that toolbox.”
Professor Jonathan Weber from Imperial College London, PrEPVacc sponsor, highlighted the study was “very well-designed”. Professor Weber thanked the hard-working staff and community members who contributed to the study.
“While it is clear that the vaccines do not produce a protective effect, we are confronted by this most unexpected results in the placebo arm.”
Member of the Community Working Group at the SAMRC Verulam site in South Africa, Xoliswa Nomvungu, emphasised that “community engagement is imperative in all phases of research”.
“In the PrEPVacc trial there have been positive community interactions so that people were well informed on developments, expectations, and transparency. A key take-home message from PrEPVacc is that adherence to available oral PrEP can prevent one from acquiring the HIV virus.”
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