Study: Further insight into Merck HIV vax infection increase

Preventive vaccines are designed to prevent disease. As they say in the U.K.--it does exactly what it says on the tin. Or it should. However, a recent study published in the Journal of Infectious Disease confirmed that a vaccine study halted in 2007 showed an increased risk of infection in the first 18 months for subgroups of the men who were vaccinated, but that this difference disappeared after 18 months.

The STEP Study was a Phase IIb trial of Merck's ($MRK) V520, an HIV vaccine based on the adenovirus serotype 5 (Ad5, which is a cold virus). The initial analysis showed that the vaccine was not effective, and once the trial was shut down, an interim analysis showed that people who received the vaccine were more likely to became infected than the people who received the placebo (the dummy vaccination).

The researchers, led by the Fred Hutchinson Cancer Research Center, carried out a more in-depth and long-term analysis of the results. Their results confirmed that 18 months after the end of the study, men who had antibodies that neutralized the Ad5 cold virus, or who had not been circumcised, or both, were two-to-four times more likely to catch HIV compared with the other groups. These men were no more likely to be involved in risky behaviors, such as unprotected sex, than those in the placebo group. After 18 months, this risk fell to be the same as placebo.

The vaccine did not contain any HIV; it delivered HIV genes using a cold virus vector. It's still not clear why the infection risk increased, and why it then fell, according to Ann Duerr, M.D., a member of the Vaccine and Infectious Disease Division of Fred Hutchinson Cancer Research Center, who led the data analysis. "There seems to be some kind of biologic phenomena that affects infection risk," she said.

The researchers found no increased risk of infection in men who were circumcised and had no antibodies against Ad5, and this means that this group of men can receive other Ad5-based HIV vaccines. Duerr added, however, that scientists need a better understanding of what happened biologically to men who became infected before those who are uncircumcised or seropositive for Ad 5 are enrolled in future vaccine trials in which the adenovirus serotype 5 vector is used.

The failure of Merck's vaccine caused chaos in HIV vaccine research for a while, but things seem to be back on track, with vaccines in development worldwide for the prevention (and the treatment) of HIV infection, from preclinical to clinical trials. Sometimes trials that are unsuccessful turn out to provide a lot of insight--hopefully that will be true of the V520 trial too.

- read the press release
- see the abstract

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