Scientific and policy challenges to development of an AIDS vaccine.

24 years since the identifi cation of HIV as the causal agent of AIDS, the pandemic continues to outpace attempts at control. The response to HIV/AIDS has been inadequate, and has consisted of crisis management rather than purposeful public health policies, because of the early silent spread of the virus, its high incidence in high-risk populations, its uniformly fatal outcome if not treated, and its global proliferation. However, an unprecedented commitment to control HIV has begun. In 2005, G8 leaders agreed to provide prevention and treatment to all those in need by 2010. But, however well intended, a universal treatment paradigm is unsustainable. UNAIDS predicts that more than US$9 billion will be needed in the next 2 years to fund AIDS treatment and care in the developing world alone. Estimates suggest that for each person who starts antiretroviral treatment, at least six people are newly infected with HIV. Thus, even if existing programmes are rapidly expanded, with increases in fi nancing, infrastructure, and human capacity, the AIDS pandemic will continue to outpace eff orts to curtail it unless we can substantially improve prevention strategies and their implementation. If we are to control and ultimately end the pandemic, a safe, eff ective, practical, inexpensive, globally accessible, preventive AIDS vaccine remains the best hope. Even an AIDS vaccine with only 50% effi cacy, which covered only 30% of the target population, could avert up to a third of the HIV infections that would otherwise occur, and thus save tens of millions of lives. After a burst of attention in the mid-1980s, the search for a vaccine was largely neglected in the 1990s (eg, only about $160 million was spent worldwide in 1994). However, in the past few years investment has risen suffi ciently to expand the vaccine development eff ort. Nearly $800 million is spent worldwide on research and development towards an AIDS vaccine every year. Development of an AIDS vaccine entails unique scientifi c challenges. The viral infection does not have many of the features that vaccinologists have traditionally used to design successful vaccines, such as induction of natural immunity to disease, known correlates of protection, and validated animal models. These novel scientifi c challenges demand a large-scale rational vaccine design eff ort, with increased and sustained fi nancial investment in research and development, and innovative forms of scientifi c organisation and collaboration. Such an eff ort is beginning. However, we believe even greater scale, commitment, and innovation will be needed to solve the scientifi c questions that impede development and testing of improved vaccine candidates. We outline key scientifi c and policy questions that must be successfully addressed to accelerate development of a safe and eff ective AIDS vaccine.