In a groundbreaking development in the fight against HIV/AIDS, a new trial known as PrEPVacc is underway, sparking hope for an effective HIV vaccine. This trial, described as “the last roll of the dice” for this decade’s HIV vaccine efforts, is now in its advanced stages, raising expectations and concerns within the medical community.
The Quest for an HIV Vaccine
HIV, the virus responsible for AIDS, was identified nearly 40 years ago, but to this day, a working vaccine remains elusive. While antiretroviral treatments are available, their accessibility varies, leading to approximately 630,000 AIDS-related deaths globally in 2022. Moreover, 39 million people worldwide are living with HIV, including 1.3 million newly infected individuals in the past year.
The PrEPVacc trial aims to change this narrative by testing two vaccines alongside two forms of pre-exposure prophylaxis (PrEP). This combination approach not only assesses vaccine efficacy but also offers protection to prevent HIV transmission. The trial, led by African scientists with international support, could usher in a new era of vaccine development if successful. However, failure could mean a setback for HIV vaccine research.
Learning from Past Trials
The journey to find an effective HIV vaccine has been fraught with disappointments. Several promising trials, including HVTN 702 (“Uhambo”), HVTN 705 (“Imbokodo”), and HVTN 706 (“Mosaico”), were discontinued due to their ineffectiveness in preventing HIV. Only one clinical trial, conducted in Thailand in 2009, showed modest effectiveness, with an efficacy rate of about 30%. To deem PrEPVacc a success, either of the two vaccines being tested must achieve an efficacy rate of at least 70%.
One vaccine combines synthetic HIV DNA with a protein base, while the other utilizes DNA, MVA (a weakened pox virus), and a protein base, similar to the approach used in the RV144 vaccine. Although PrEPVacc builds on RV144’s foundation, it represents an evolutionary step in HIV vaccine research, not a revolution. Jonathan Weber, the lead applicant and coordinator of PrEPVacc, described these vaccines as the best that current medical science can provide.
The PrEPVacc Trial
The PrEPVacc trial commenced enrollment in December 2020 and concluded with 1,513 participants by March 2023. Participants, aged 18-40, reside in South Africa, Uganda, or Tanzania—countries with high HIV/AIDS rates. These locations were chosen not only for their HIV prevalence but also for their experience in conducting HIV prevention studies and their strong community connections.
Funding for PrEPVacc came from the European Union-sponsored EDCTP, highlighting the importance of an African-led study conducted on the African continent. The trial’s success relies on the collaboration of African scientists and resources.
Combining Vaccines and PrEP
In this randomized trial, each participant receives four injections of either vaccine A or B or a saline placebo over 48 weeks. They also take PrEP daily until week 26, after the third injection, optimizing the immune response. PrEP is known to significantly reduce the risk of HIV transmission during sex and among people who inject drugs.
PrEPVacc is unique in its approach, distributing two forms of PrEP pills: Truvada and Descovy. The trial assesses if Descovy, which currently holds FDA approval for use by men, offers the same or better effectiveness. Combining a trial HIV vaccine with PrEP is a novel strategy and a first in the field.
PrEP usage in Africa faces significant challenges, including access, acceptance, and social stigma. Access to PrEP is often limited, and stigma surrounding HIV can deter individuals from seeking medication. The hope is that by providing PrEP within the trial, participants will see it as a viable and acceptable option for HIV prevention.
After 26 weeks, trial participants have the option to access PrEP from public health facilities, but long-term use remains a challenge. Issues with consistent PrEP use persist, highlighting the need for improved education and accessibility.
The Road Ahead
The PrEPVacc trial is on track, with more than half of the participants in some locations having already received all four injections. The results, scheduled for release in the fourth quarter of 2024, are eagerly awaited.
Notably, the trial team remains blind to the data, ensuring objectivity. Early data monitoring has not prompted trial halts, as seen in previous trials. This is an encouraging sign, although experts remain cautiously optimistic about the vaccines’ potential efficacy.
Should one or both vaccines prove effective, further trials will likely involve international collaboration. However, if they fall short, it may be back to the drawing board for HIV vaccine development.
The Future of HIV Vaccine Research
While PrEPVacc represents a crucial milestone, it may not be the last effort in this decade to find an HIV vaccine. Promising avenues, such as germline targeting and mRNA-based vaccines, offer new possibilities. These approaches, although in early stages of testing, hold the potential to stimulate the production of broadly neutralizing antibodies against HIV.
Despite the challenges and uncertainties, the fight against HIV continues, fueled by the dedication of researchers and participants like Luwano Geofrey. Geofrey’s commitment to the trial, despite the hurdles he faced, reflects the determination of those involved in the search for an HIV vaccine.
As the world awaits the results of the PrEPVacc trial, one thing is clear: the quest for an HIV vaccine is far from over. Whether this endeavor marks the last roll of the dice for this decade remains to be seen, but the pursuit of a vaccine continues to be a beacon of hope in the fight against HIV/AIDS.
The PrEPVacc trial holds both hope and challenges in the quest for an effective HIV vaccine. While past trials have faced setbacks, the unique combination of vaccines and PrEP in this trial offers new possibilities. As the trial progresses and results are expected in 2024, the world watches with bated breath, hoping that this could be the breakthrough we’ve long awaited in the battle against HIV/AIDS.