Researchers told an open scientific meeting in Seattle, Washington, on Monday, November 6th, that a clinical trial on Merck’s prototype HIV vaccine V520 had been halted because interim results suggested there was an apparent increased risk of becoming infected with HIV in the vaccine group compared with the placebo group.
The vaccine failed to prevent infection in volunteers who were not infected with HIV at the start of the trial and neither did it reduce the amount of HIV virus circulating in the blood of volunteers who became infected with HIV during the course of the trial.
Representatives from Merck and the National Institute of Allergy and Infectious Diseases (NIAID, part of the US National Institutes of Health) said the results of the STEP trial could be due to chance differences in the vaccine and placebo group. Further analysis will hopefully yield better information they said.
The people who took part in the trial will receive counselling, said Merck and NIAID investigators. But the vaccine itself does not cause infection, they said, because it only contains fragments of the HIV virus.
STEP was an international, multi-site Phase II clinical trial involving high risk HIV-negative volunteeers aged 18 to 45. At first, the trial was stopped because it was not showing the vaccine to be effective.
Another trial based in South Africa, called Phambili or HVTN503, has also been halted, because of the results from the STEP trial, said the Merck and NIAID investigators.
The researchers said the higher risk of HIV infection was observed among participants with an existing immunity to the common cold virus adenovirus type 5. This cold virus was used as a carrier in the vaccine, and the investigators suggested one explanation for its failure could be because the participants’ immune systems may have reacted so as to reduce defences against HIV itself.
The STEP trial results showed that of the 741 volunteers in the vaccine arm of the study, 24 developed HIV infection. They had received at least one of the three doses of the vaccine. Among the 762 volunteers in the placebo arm of the trial, 21 developed HIV.
The differences could be a statistical anomaly due to chance differences between the groups, said the researchers. For instance there could be differences in rates of circumcision, known to affect HIV infection susceptibility, and rates of exposure to HIV as a result of sexual practices.
According to Merck “most of these analyses are considered exploratory in nature, and the reasons for this result are still being studied”.
Also, all but one of the infected volunteers were male, primarily men who reported having sex with other men. This means the trial had few results on the vaccine’s effect on women or heterosexual men.
The researchers reminded the meeting that the vaccine itself cannot cause HIV infection. The vaccine contains three types of carrier, each based on a version of the common cold virus adenovirus type 5 (Ad5) that had been altered to stop it replicating. Each of the three versions carries a synthetically produced HIV gene fragment.
The vaccine trial was sponsored by Merck, the National Institute for Allergy and Infectious Diseases and the HIV Vaccine Trials Network (HVTN).
Click here for a full and detailed account of the trial and results (Merck statement).
Click here for more information on HIV Vaccine Trials Network (HVTN).
Written by: Catharine Paddock