Experimental HIV vaccines fail to reduce infections in trial

Key takeaways:

• Two HIV vaccine regimens failed to reduce new infections during a 3-year trial in Africa.
• The trial was stopped last year based on advice from independent advisors.

Two experimental HIV vaccine regimens failed to reduce infections in a 3-year trial in eastern and southern Africa compared with participants who were taking a placebo, some of whom were on oral PrEP, according to a study.

Leaders of the PrEPVacc study announced last December that they had stopped vaccinating participants in the trial after finding that there was “little or no chance” the two vaccine regimens would prevent HIV. The decision was based on recommendations from an independent data monitoring committee.

It was the latest in a string of recent failures in HIV vaccine research, although there have been breakthroughs elsewhere in HIV prevention science.

Final results from PrEPVacc were presented at the International AIDS Conference in Munich. They showed there were more infections in the two vaccine arms of the trial than the placebo arms, study leaders explained in a press release. According to the release, there was an unusually low rate of HIV infection in the placebo arms that “does not appear to be explained by a difference in the use of condoms or” PrEP.

“While it is clear that the vaccines do not produce a protective effect, we are confronted by this most unexpected result in the placebo arm, where the extremely low incidence of HIV infection is at odds with the incidence found in our registration cohort,” Jonathan Weber, FMedSci, FRCP, FRCPath CBE, director of the Imperial College Academic Health Science Centre at Imperial College London, said in the release.

“We need to await the results of further experiments to understand how this surprising set of results arose, if not by chance alone,” he said.

From 2020 to 2024, researchers enrolled more than 1,500 healthy adults aged 18 to 40 years in Masaka, Uganda; Mbeya and Dar es Salaam in Tanzania; and Durban, South Africa, 87% of whom were women.

They assigned participants randomly into three groups: one group received a combined DNA vaccine (DNA-HIV-PT123) and protein vaccine (AIDSVAX B/E), one received the DNA vaccine, a modified nondividing virus vector (MVA-CMDR) and a protein-based vaccine (CN54gp140), and a placebo group received saline over the course of a four-injection schedule of visits.

Researchers counseled participants on the benefits of oral PrEP and offered it to them from their enrollment through 2 weeks after their third vaccine dose, according to the release.

Because of challenges arising from the COVID-19 pandemic, the researchers in June 2022 discontinued enrollment in the MVA-CMDR/CN54gp140-combination vaccine arm.

According to the researchers, among participants who received at least three doses of the DAN/AIDSVAX B/E combination, 11 of 532 people acquired HIV, for an incidence rate of 1.73 infections per 100 person-years — more than three times the rate in the placebo group.

Among participants who received the MVA-CMDR/CN54gp140 combination, nine of 244 participants acquired HIV, for an incidence rate of 2.38 infections per 100 person-years, compared with an incidence rate of 0.51 infections per 100 person-years in the placebo arm.

“The positive news for our communities is that repeated risk reduction counseling and use of proven HIV prevention tools helps people navigate their risks better,” Eugene Ruzagira, PhD, lead researcher for PrEPVacc and senior scientist at the Medical Research Council/Uganda Research Institute and London School of Hygiene & Tropical Medicine’s Uganda Research Unit on AIDS, said when presenting the study at AIDS 2024.

“The number of new infections has fallen throughout the 6 years we have been monitoring the HIV incidence in each study community. ... We look forward to the findings from PrEPVacc’s integrated social science research and the results of the PrEP study in PrEPVacc to come later this year,” Ruzagira said.

References:

• Ruzagira E, et al. Abstract OAC0806. Presented at International AIDS Conference; July 22-26, 2024; Munich.
• HIV vaccines tested in PrEPVacc fail to reduce infections. https://www.prepvacc.org/news/hiv-vaccines-tested-in-prepvacc-fail-to-reduce-infections-23-july-news-release. Published July 23, 2024. Accessed July 31, 2024.
• Experimental HIV vaccine regimens likely to be ineffective in preventing HIV acquisition, PrEPVacc study reports. https://www.prepvacc.org/news/experimental-hiv-vaccine-regimens-likely-to-be-ineffective-6-dec-2023-news-release. Published Dec. 6, 2023. Accessed Aug. 1, 2024.