Merck’s investigational HIV vaccine fails in study

The vaccine, V520, cannot cause HIV infection, Merck said, and the 3,000 volunteers were all HIV-negative at the start of the study. The vaccine was created using a mixture of three components, each made with a replication-defective version of one of the common cold viruses, adenovirus type 5 (Ad5), which served as a carrier, or delivery vector, for three synthetically produced HIV genes.

The current results suggest that those who received the vaccine might have an increased susceptibility to acquiring HIV infection, particularly those volunteers who had higher levels of pre-existing immunity to Ad5 because of prior natural exposure to Ad5. However, Merck said that there are a number of confounding factors that make it very difficult to draw conclusions about this finding.

In a post-hoc analysis of the overall study population, a total of 49 cases of HIV infection were seen among the 914 male volunteers in the vaccine group compared to 33 cases of HIV infection among the 922 male volunteers in the placebo group.

Although the study was not designed to assess whether study volunteers with high Ad5 immunity who received vaccine were more likely to acquire HIV infection, the difference in the number of cases of HIV infection between the vaccine and placebo groups was more pronounced among volunteers with high Ad5 immunity. Among the 778 male volunteers who had high levels of pre-existing immunity to Ad5 (greater than 200 units), 21 cases of HIV infection were observed in those who had received vaccine and nine cases of HIV infection were observed in the volunteers who had received placebo.

In addition, the vaccine was not effective based on the analysis of the second primary endpoint, viral load levels in study volunteers who became HIV infected. HIV RNA levels approximately eight to 12 weeks after diagnosis of infection were generally similar in the vaccine and the placebo arms in the modified intention to treat population.

Study volunteers are being counseled about the possibility that those who received the vaccine may be more susceptible to developing HIV infection when exposed to HIV. The trial included multiple clinical trial sites in North and South America, the Caribbean and Australia, where HIV subtype B, the subtype of HIV from which the HIV genes included in the vaccine, is predominant.

Keith Gottesdiener, vice president for vaccine and infectious disease clinical research, Merck Research Laboratories, said: “The data from this trial are remarkably complex. We are analyzing the data to try to determine if the results are due to immune responses induced by the vaccine, differences in study populations, or some other biological phenomenon we don’t yet understand, or simply due to chance.”