After about 18 months, risk level decreased to that of volunteers who received a placebo
A long-term follow-up analysis of participants in the Step Study, an international HIV-vaccine trial, has confirmed that certain subgroups of male study participants were at higher risk of becoming infected after receiving the experimental vaccine compared to those who received a placebo. The vaccine used in the study did not contain the HIV virus, but it did contain HIV genes which were delivered to cells using a vector that employed a type of cold virus known as adenovirus serotype 5 (Ad5).
Of the 1,836 men examined in this study, 172 became infected with HIV. Within 18 months of enrollment or one year after the last vaccination, men who had neutralizing antibodies to Ad5 or who were uncircumcised, or both, had a two- to four-fold increased risk of acquiring an HIV infection, according to findings published in the May 4 online edition issue of the Journal of Infectious Disease.
However, the study also found that the risk level waned after about 18 months to be equal to that of volunteers who received a placebo.
Why this association occurred, what the biological mechanisms were and why the risk of infection lessened with time are unknown and require more study, 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 current study indicated that self-reported risk behaviors, such as unprotected sex, did not differ significantly between the vaccine and placebo arms of the Step trial.
The research also confirmed there was no elevated risk of infection in vaccinated men who were circumcised and who were Ad 5 seronegative (men who had no neutralizing antibodies to the adenovirus vector used in the vaccine). An earlier interim analysis of the Step Study data, done after immunizations in the vaccine trial were halted in 2007, also detected this relationship between Ad5 sero-status and vaccine-associated HIV risk. Today, only men who are circumcised and Ad5 seronegative are eligible to receive experimental HIV vaccines that use the adenovirus serotype 5 as a biological delivery mechanism.