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The HIV vaccine world has been in turmoil ever since the fall of 2007, when Step Study investigators first reported the unexpected failure of the Merck adenovirus serotype 5 (Ad5) HIV vaccine (AIDS Clin Care Oct 1 2007). Although the lack of protection offered by this vaccine was certainly disappointing, the larger, more perplexing issue has been the increase in risk seen among vaccine recipients who were both Ad5-seropositive and uncircumcised (AIDS Clin Care Dec 8 2008). Detailed analyses from the trial have yielded some clues about the failure of the vaccine — for example, we now know that only one third of vaccinees mounted both CD4 and CD8 HIV-specific T-cell responses following vaccination — but we might never have a complete explanat…