PrEPVacc is an African-led and European-funded HIV prevention clinical trial conducted in four African countries from 2018 to 2022. It is the first vaccine trial that attempts to incorporate pre-exposure prophylaxis (PrEP) in a realistic way in addition to the vaccine candidates tested; it proposes an alternative approach to design HIV vaccine trials in the era of PrEP, which has been proven effective to prevent HIV infection in itself.
It is also the first HIV vaccine efficacy trial to be funded by the European Union.
This trial will evaluate two experimental HIV vaccine combinations for the prevention of HIV infection, each compared against a placebo. It will also evaluate whether a new formulation of the drugs used for PrEP (Descovy: tenofovir alafenamide, TAF, plus emtricitabine, FTC) is as effective as the current formulation approved for PrEP (Truvada: tenofovir disoproxil fumarate, TDF, plus FTC).
In the trial, we will be using two innovative study designs. The first is an adaptive trial design (multi-arm, multi-stage, or MAMS) which allows for the evaluation of multiple vaccine regimens concurrently and includes early evaluation with the possibility of discontinuing unpromising vaccine combinations. This adaptive trial design is novel in the HIV vaccine field and makes trials more efficient. This adaptive trial design is novel in the HIV vaccine field; we will generate data on HIV vaccine efficacy, investigate correlates of protection, and address adherence and attitudes to PrEP.
The second is the use of the “averted infections ratio methodology”, which estimates infections averted by a new form of treatment compared with the standard treatment, using an estimate of incidence in the placebo arm. The adoption of this analytic method also allows use of smaller sample sizes.
The PrEPVacc trial will either rule out or encourage further development of the combination regimens tested for preventing HIV. PrEPVacc will trial two regimens: one combining DNA with protein-based vaccines; and one combining DNA, MVA and protein-based vaccines. Both have been evaluated in multiple Phase I/II clinical trials in the United States, Europe and Africa, and have demonstrated their safety and ability to induce immune responses.
Participants will be offered PrEP through the study to cover the period spanning the first three immunisations as this is how we believe PrEP would be applied in an immunization programme – protecting people until the vaccines are working. When assessing vaccine efficacy in the PrEPVacc trial, only HIV infections that happen after the first three vaccines (given over six months) will be counted.
PrEPVacc will inform the field about whether the vaccine regimens can protect against HIV infection. If PrEPVacc demonstrates protection against HIV, we will study immune correlates of protection, which tell us which type of immune responses induced by the vaccines correlate with protection against infection. Studies of immune correlates can provide invaluable information for future vaccine design and clinical development.
One of our challenges is addressing HIV-related stigma that can make it very difficult to find enough people willing to participate in HIV prevention trials. HIV vaccine trial participants may have to attend clinics where people living with HIV are treated, and may fear that people will think that they have HIV. I have worked with participants who did not want to be seen with our research teams or at our research clinics – even if they were HIV negative. Whispers still circulate in many communities, and it can make our work more complicated. It takes a lot of hard work. But usually, when you go out to the communities and when you work with these communities, taking the necessary time to do so, people are really interested and willing to participate.
I have seen first-hand how HIV has affected my own country, Uganda. Although a lot has been achieved with antiretroviral treatment and PrEP, people still suffer on a daily basis in communities in Uganda. Here, around 1.3 million people are living with HIV. Each year, 26,000 people die from AIDS-related illnesses, and there are 50,000 new infections, including 7,600 in children younger than 14 years. Also, nearly one-third of people living with HIV have not initiated antiretroviral drugs.
That’s why this new trial is so important. If we find an effective vaccine, a few shots will be enough to prevent HIV for a lifetime.