Step study participants could enroll in HVTN 504 for follow-up until the end of 2009, or for up to four years from their original enrollment. The objectives of the study analysis included measuring the vaccine’s effect on HIV infection, studying interaction effects of baseline Ad5 sero-status and circumcision status on vaccine-induced HIV infection risk, and evaluating possible changes of relative risk (V:P) with time since vaccination. Duerr and colleagues found, over the entire follow-up period, that there was a higher risk of HIV infection among the vaccine recipients versus placebo recipients (Hazard Ratio (HR) 1.44, 95% confidence interval (CI): [1.05-1.97]). In the first 18 months, there was a significant three-way interaction between circumcision status, Ad5 serostatus, and treatment (p= 0.04), which suggests a joint effect of the two baseline factors on the relative risk of HIV infection. Uncircumcised, Ad5 seropositive men had an HR that was 4 times greater in the vaccine recipients, compared to the placebo recipients. Concerning the vaccine’s effect on HIV infection over time, the elevated risk of infection in the vaccine group (uncircumcised and/or Ad5 seropositive men) during the first 18 months appeared to wane over time.
The conclusions of Duerr and colleagues extend the findings of the initial analyses in the Step study, confirming the increased vaccine-associated risk of infection during the first 18 months, which decreased over time. The authors’ results also show limitations associated with the use of Ad5 vectored vaccines in populations of uncircumcised and/or Ad5 seropositive men. A biologic effect of prior Ad5 immunity on susceptibility to HIV infection may be suggested, but further study is necessary to prove and define these mechanisms.
Duerr A, Huang Y, Buchbinder S, Coombs RW, Sanchez J, Del Rio C, Casapia M, Santiago S, Gilbert P, Corey L, Robertson MN; for the Step/ HVTN 504 study team. 2012. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step study). Journal of Infectious Diseases. May 4; doi: 10.1093/infdis/jis342