'End of This Phase': Trial Halts Testing of HIV Vaccine Candidates

The PrEPVacc trial has stopped administering two investigational HIV vaccines that showed no efficacy in preventing infection, investigators announced on Wednesday during the International Conference on AIDS and STIs in Africa in Zimbabwe.

"Vaccinations to PrEPVacc trial participants have been stopped because an analysis of the data collected so far by our Independent Data Monitoring Committee has led them to conclude that there is little or no chance of demonstrating that the vaccines we are testing are reducing the risk of acquiring HIV," said Eugene Ruzagira, PhD, of the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, in a press release.

Developing an effective HIV vaccine has proven to be a major, ongoing hurdle in the fight against AIDS. It has been over a decade since the RV144 trial demonstrated modest efficacy in reducing HIV acquisition by 31% at 3 years, and numerous other HIV vaccine trials have failed. Most recently, the MOSAICO HIV vaccine trial was abruptly halted in early 2023, due to lack of efficacy.

"This is hardly the first time that an HIV vaccine study has been stopped early for reasons of futility," Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women's Hospital in Boston, told MedPage Today in an interview. "What I expect we'll see is that the acquisition of HIV is comparable in vaccine and nonvaccine arms" when the final results of the PrEPVacc trial are posted.

"This is kind of the end of this phase of [HIV] vaccine research studies. There's really nothing else going on now, just showing how difficult this scientific challenge has been to make an HIV vaccine," noted Sax, who was not involved in the study.

"Ironically, the fact that we have other very effective prevention measures is making finding a vaccine more difficult," he added.

PrEPVacc is an African-led, European-supported HIV prevention study that has been evaluating two novel HIV vaccines, plus a relatively newer form of oral pre-exposure prophylaxis (PrEP), emtricitabine/tenofovir alafenamide fumarate (FTC/TAF). The trial enrolled 1,512 volunteers ages 18 to 40 at high risk for acquiring HIV across four sites in Uganda, Tanzania, and South Africa. The majority (87%) of enrollees are women.

The first participants in the clinical trial were enrolled in December 2020 and enrollment continued until March 2023. Participants received injections of a combination DNA vaccine and protein-based vaccine (AIDSVAX); a combination DNA, MVA, and protein-based vaccine (CN54gp140); or placebo. Participants received four injections in each regimen arm.

Participants also were assigned to receive either FTC/TAF or emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) to assess if FTC/TAF was noninferior or more effective than TDF/FTC. By October, 1,016 participants had received all four vaccinations.

The oral PrEP component of the study will be continued until completion. All participants will be followed for at least an additional 6 months after the last vaccination to gather additional safety data, as well as to provide HIV testing and referral for ongoing care.

The PrEPVacc trial will at least provide useful data from this part of the study to guide the use of oral PrEP regimens, researchers said.

"While we await the final results and analysis of individual products, I believe that our interim result puts this generation of putative HIV vaccines to bed," Jonathan Weber, MB BChir, PhD, of Imperial College London, the lead coordinator of PrEPVacc, said in a statement.

Any further vaccinations were halted as of November 22, when it became apparent that the trial would be discontinued. No safety concerns have been reported regarding the vaccines. Full results of the vaccine trial will be reported in the second half of 2024, according to the PrEPVacc investigators.

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