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Michael NL, Robb ML. Lancet Infect Dis 2014; 14: 361–362

Following successful pre-clinical and phase 1 trials for adenovirus type 5 (Ad5)-vectored DNA vaccine encoding HIV-1 subtype B gag, pol, and nef proteins (Merck & Co., Inc.), phase efficacy trials named the Step study and Phambili ('moving forward' in the Xhosa language) were rolled out. Interim analysis for the Step study (cohort of men who had sex with men in the Americas, Caribbean and Australasia), found that this vaccine not only failed to have a protective effect but indeed resulted in excess HIV infection. As a consequence of the findings from the Step study, there was early closure of the Phambili study with participants unmasked to treatment allocation. The Phambili study recruited South African participants at high risk of heterosexually transmitted HIV infection. Not only were the results from the Phambili study also disappointing, but, of note, excess HIV infections were detected not shortly after, but several years after vaccination. The authors conclude there is now sufficient evidence to 'abandon the use of recombinant Ad5 vectors in future HIV vaccine development'.