A randomized, double-blind, placebo-controlled clinical trial found no benefit for a therapeutic HIV vaccine, but could offer researchers much needed insights for future cure efforts. The authors say their results represent yet another addition to the burgeoning body of evidence that therapeutic vaccination fails to help patients suppress HIV in the absence of antiretroviral therapy (ART). Although ART has provided tremendous benefits for prolonging lifespans of those infected with HIV, the regimens have not been able to eliminate the virus from its reservoirs within the body. Therapeutic vaccination has emerged as a potential strategy to boost people’s own immune responses against HIV so they can control the virus without ART. To study the effectiveness of such an approach, Michael Sneller, Anthony Fauci and colleagues recruited a cohort of HIV-infected individuals from the United States and Canada who had initiated ART shortly after their initial diagnosis. During a 36-week period where all participants continued ART treatment, 14 people received four injections of a therapeutic HIV vaccine and 15 individuals were administered saline as a control. When ART was discontinued for 16 weeks under the supervision of the researchers, there was no difference observed in viral rebound between placebo and vaccine groups. Surprisingly, four people in the placebo group exhibited spontaneous HIV suppression – a substantially greater proportion than would be predicted by the estimated prevalence of so-called “elite HIV controllers” in the general population. A related Focus by Nelson Michael discusses how these findings further demonstrate the value and importance of well-designed placebo-controlled trials.