A trial is underway that could be ‘the last roll of the dice’ for an HIV vaccine this decade

A novel trial that has been described as “the last roll of the dice” for a generation of HIV vaccines has entered its latter stages.

Called PrEPVacc, the trial is testing two vaccines alongside two forms of pre-exposure prophylaxis (PrEP) to test vaccine efficacy while offering protection to prevent the spread of HIV.

African-led and coordinated out of Entebbe, Uganda, with international support, its success could mark the start of a new phase of vaccine development. Should it fail, it could also see immunologists give up on a generation of vaccines.

Nearly 40 years since HIV was identified as the cause of AIDS, and 36 years since the first HIV vaccine trial, the medical community still does not have a working vaccine. Although antiretroviral treatments are well established, access varies. UNAIDS estimates 630,000 people died from AIDS-related illness globally in 2022, while 39 million people are living with HIV, including 1.3 million people newly infected last year.

The hope is that PrEPVacc will succeed where other trials have fallen short – most recently HVTN 702 (dubbed “Uhambo”), halted in February 2020, HVTN 705 (“Imbokodo”), discontinued in 2021 and HVTN 706 (“Mosaico”) in 2023, all of which were found to be safe but ineffective at preventing HIV.

Only one clinical trial, which took place in Thailand with results published in 2009, has been found to show modest effectiveness at preventing HIV infection. The efficacy of that vaccine, RV144, was about 30% (although the findings continue to be debated). For PrEPVacc to be considered a success, either of the two vaccines being tested will need to achieve an efficacy of at least 70%.

One vaccine combines pieces of synthetic HIV DNA with a protein base, while the other combines DNA, MVA (a weakened pox virus) and a protein base, like that used in RV144.

“This is an evolution (of RV144), not a revolution,” said Jonathan Weber, lead applicant and coordinator of PrEPVacc, and director of the Imperial College Academic Health Science Centre in London. “These are both regimens which have never gone into efficacy study before,” he added, describing the vaccines as “the best we feel, at the moment, that medical science can provide.”

The Iwambi area of Mbeya, Tanzania. Mbeya is one of four sites where the PrEPVacc study has enrolled participants. Tanzania, like South Africa and Uganda, ranks highly in global HIV/AIDs prevalence in adults.

The clinical trial began enrollment December 2020 and signed up the last of its 1,513 participants in March 2023. The participants are all between 18-40 years old and live in South Africa, Uganda or Tanzania.

All three countries have high rates of HIV/AIDS in adults, sitting within the top 15 countries in the world per 2021 estimates. But that is not necessarily why they were chosen to participate, said Eugene Ruzagira, PrEPVacc trial director.

Ruzagira is himself Ugandan, based in Entebbe at the Medical Research Council/Uganda Virus Research Institute, and oversees a team of researchers at trial sites in Durban, South Africa, Masaka, Uganda, and Dar es Salam and Mbeya, Tanzania. These locations, he explained, “had experience doing HIV prevention studies, not only vaccine trials, have established very good connections with the communities, and have the infrastructure we require.”

Though funding for PrEPVacc came from the European Union-sponsored EDCTP, “this genuinely needed to be an African study led by Africans and coordinated in Africa, where the data is analyzed in Africa and the laboratory work is done in Africa,” said Weber.

“It’s about time,” Ruzagira said. “We’ve had a few decades of preparation.”

Prosthetics —

The world's first prosthetic toe dates to an Egyptian mummy. The Romans and the Greeks wrote about prosthetic arms and legs. But artificial limbs didn't gain a lot of movement and functionality until the 1500s, with hands that had the ability to grasp and legs that were able to kneel. While the technology continued to develop, the injuries of the Civil War would push Americans to the forefront of prosthetics. Today, technology is taking prosthetics to new levels: bionic limbs with natural feel, and built simply with 3-D printers.

Vaccines —

People tried to inoculate themselves with smallpox as far back as 1,000 A.D. in China by scratching smallpox sores onto the skin. However, it wasn't until 1796 that English doctor Edward Jenner was able to use cowpox as a vaccine against the deadly disease. Vaccines would make another leap 50 years later, with the development of the hypodermic needle. Up until that point, a lancet had to be used. The needle was key to helping Louis Pasteur develop a successful rabies vaccine. By the 1920s, vaccines for diphtheria, tetanus, whooping cough and tuberculosis were available. By 1980, smallpox was eradicated from the world, and polio is almost eliminated from the planet.

Thermometers —

While Galileo is frequently credited as the inventor of the thermometer, it wasn't until the mid-1800s (the era of the one pictured) that doctors were able to use thermometers to measure people's temperatures. Before that thermometers were not only large and cumbersome, but they also were not able to diagnose actual temperature grades. In 1866, a convenient 6-inch thermometer was invented. The early varieties were made of thin tubes of glass with mercury, and were mounted to ivory or wood.

Face transplants —

Plastic surgeons date the first nose job as far back as the 1400s, but developments in this area of surgery would have to wait until the practice of the skin graft was honed in the late 1800s. Even then, it would take another two centuries before doctors were able to apply this technology to transplanting parts of the face. French doctors did a partial facial transplant in 2005, and three years later, doctors at the Cleveland Clinic performed the world's first full facial transplant.

Anesthetics —

Herbal mixtures using opium poppy were used as early as 4,000 B.C., but it wouldn't be administered intravenously until 1659 -- first delivered to a dog's vein using a goose quill. But in 1771, nitrous oxide was discovered, and in 1800, Humphry Davy wrote "as nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place." It was first used for tooth extractions. By 1847, anesthetics were used for labor and other surgeries.

Seat belts —

One of the greatest life savers of our time, the seat belt reduces the probability of driving fatalities by about 50%. In the United States alone, it prevents about 15,000 deaths annually. The three-point seat belt, patented and introduced by Volvo in 1959, was filed under an open patent, making the technology available to any company, because the developers knew the kind of safety impact it could make. By 1968 all new cars in America had modern seat belts.

Aspirin —

Aspirin is a remedy as old as time. Ancient Egyptians are known to have used willow bark to alleviate their aches and pains without knowing that it was salicylic acid, the natural version of aspirin, that reduced body temperature and inflammation. But it wasn't until the 19th century that a synthetic version of the aci