Well-intentioned trials of HIV vaccination could lead to hundreds of thousands of unanticipated infections because of a sting in the tail of the vaccine, according to a new study. A team led by Joshua Herbeck from the University of Washington used mathematical modelling to estimate the rate at which HIV vaccination caused vaccine-resistant virus to evolve, a process known as adaptation. In a scenario where 70% of the population was vaccinated, the researchers calculated that within 10 years up to 250,000 new HIV cases could arise solely as a result of resistant-strains. “Our results predict that HIV adaptation in response to vaccination may have a considerable, and detrimental, public health impact,” they write in the article, which was lodged on pre-print website biorxiv in late February, ahead of peer review. The issue is of particular concern in South Africa, where the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates 19.2% of adults live with HIV. South Africa is also the venue for HVTN 702, touted as the largest HIV vaccination trial ever to take place in that country. Launched in November and partially funded by the National Institute of Health, HVTN 702 is scheduled to enrol 5400 men and women. Previous HIV vaccination trials have produced underwhelming results. The RV144 trial in Thailand which ran from 2003 to 2006, for example, was only 31% effective in preventing the virus. The researchers analysed the RV144 results and found significant genetic differences between HIV strains in participants who received the vaccine and those who got a placebo. “(Genetic) variation in HIV can be associated with differential infection rates in a vaccinated population, making viral adaptation a potential outcome,” the authors write. In initial modelling of a sensitive strain of HIV the researchers found a vaccine covering 70% of the population would prevent 40% of infections over 10 years. But worrying findings emerged when the researchers fed vaccine-resistant HIV strains into the model, a step, they argue, which was critically omitted in earlier models. “In all simulations ... resistant virus increased in proportion after vaccine rollout,” the researchers continue. And as greater resistance emerged, vaccine effectiveness dropped. Commenting on the findings, Professor Stephen Kent from Melbourne’s Doherty Institute said, “It is likely that partially efficacious vaccines will be first to market and will lead to some development of vaccine resistant strains, but the net effect should still be very beneficial while more fully effective vaccines are being developed.” The study authors warn, however, that HIV vaccine development needs to consider the consequences of virus evolution. “This includes continued surveillance of viral genetic diversity, accompanied by vaccine design that limits the mutational pathways available for viral adaptation and subsequent emergence of vaccine-resistant viruses,” they state.