Roadblock: 

The HIV epidemic is taking an enormous toll in the lives of millions of people, particularly in the developing world. Developing more effective and efficient HIV prevention methods is an urgent priority. Current prevention methods, including behavior change and promotion of the use of condoms or circumcision, are only partially effective. Cellular or antibody-based approaches for traditional HIV vaccines have not yet yielded measures of efficacy for either prevention or therapy.

While antiretroviral drugs have been successful in expanding treatment to patients worldwide, current therapies do not clear the infection and so require life-long treatment to prevent the infection from progressing to more advanced forms of disease. New methods need to be discovered that can permanently eliminate infection, even in cases where effects of the virus are being controlled with current drugs.

What We Are Looking For:

The goal of this topic is to solicit new approaches to preventing or curing HIV infection. There are many points in the replication or infection cycle of the virus that might be points of effective intervention, such as: blocking the virus from entering or replicating in host cells, suppressing the production of new viable virus, eliminating infected cells, or blocking transmission between individuals. New ideas that represent alternatives to existing prevention and treatment methods and investigational approaches are needed. Similarly, we also seek novel approaches to completely eliminate the virus in infected individuals. We seek proposals “off the beaten track,” significantly radical in conception, and daring in premise.

A few of the many options to be considered include:

• New hypotheses regarding the mechanisms by which HIV causes persistent infection or disease that are explicitly linked to prevention or curative strategies;

• New approaches to modulating or enhancing the human humoral or cellular immune system, including the innate immune system, or approaches for an artificial adjunct to the immune system;

• Novel approaches and interventions that require multi-disciplinary or multi-system methods;

• Novel ways to model or track infection that are explicitly linked to prevention or cure;

• Interventions that might be administered systemically or locally that interfere with the virus at the point of infection or limit the effects of viral infection;

• Approaches that render the virus harmless to humans either before or during infection;

• New approaches that alter viral mutation so that the natural or induced immune response can succeed;

• New approaches based on a clear biological rationale that employ multiple interventions in combination for improved performance;

• New methods to determine the reservoir of virus in the infected host, including whether this is the viral archive in the host genome or low-level replication of active virus;

• New hypotheses about the relationship between HIV and co-infecting or endogenous pathogens, that offer explicit consequences for preventive or curative interventions.

For this topic, we will not consider funding for:

• Testing of novel compounds or immunological interventions without a clear hypothesis as to their effect on prevention or cure of HIV infection;

• Common approaches that are incremental advances to the field;

• Approaches based on behavior modification, or promotion of the use of condoms or circumcision;

• Approaches using microbicides currently under development or those designed with currently available anti-retroviral compounds;

• New projects on antiretroviral compounds that suppress infection, without eliminating infection, by targeting the virus or viral factors;

• Approaches to compound discovery that are not based on knowledge of the intended mechanism of action;

• Concepts previously or currently under clinical investigation.