March 2002: Grants Include Projects to Develop New Anti-HIV Drugs
In March 2002, amfAR announced basic research grant awards totaling over $2 million for new research on HIV/AIDS, including projects seeking to develop new anti-HIV drugs. More than $700,000 was awarded as part of an initiative to identify novel molecular targets and to screen large combinatorial libraries of chemical compounds for substances that could block the function of viral and cellular components essential to HIV's replication. Both approaches are expected to speed the discovery of new anti-HIV drugs.
One of amfAR’s grantees, Dr. Richard Kornbluth, recently received a GlaxoSmithKline Drug Discovery and Development Award for research funded by amfAR under its new drug targets initiative. Dr. Kornbluth’s research could lead to the development of a new class of HIV inhibitors. In the latest grant cycle, Dr. Kornbluth was awarded a grant to study groups of proteins and genetic material that cooperate to bring about the insertion of HIV’s genetic material into the cells the virus infects—with the ultimate goal of identifying chemical compounds that might prevent this process.
The Need for New Anti-HIV Drugs
Growing levels of drug resistance and the need for new classes of anti-HIV drugs are the driving forces behind amfAR’s targeted initiative to develop new anti-HIV drugs. A recent study of blood samples collected two to three years ago found that as many as three out of four HIV patients tested were infected with a viral strain that is resistant to at least one drug used to treat the disease.
Once HIV develops resistance to one medication, it becomes progressively easier for the virus to develop resistance to other drugs in the same class, or even to that entire class of drugs, e.g., protease inhibitors. People who harbor drug-resistant strains of the virus can also transmit these resistant strains to others, and those who carry drug-resistant strains of HIV are left with few, if any, treatment options.
The Foundation’s latest targeted research initiative takes an entirely new approach, focusing on (1) “accessory” genes and gene products of HIV that have been previously neglected in drug development; (2) cellular proteins that HIV needs in order to reproduce but that may not be essential to human cell function; and (3) the development of new laboratory tests to assess the activity of chemical compounds against these new targets.
The Foundation is funding efforts to study HIV’s genes and gene products, as well as specific components of human cells that are essential to HIV’s ability to infect cells and replicate. With a better understanding of these viral and cellular components, researchers will hopefully be able to develop new drugs that can prevent HIV from reproducing, reduce viral load, and slow disease progression in HIV-infected individuals. amfAR began its targeted initiative for the development of new anti-HIV drugs in February 2001.
Searching for New HIV Inhibitors
A related effort to accelerate the pace of new drug development allows researchers to screen so-called “combinatorial libraries” of tens of thousands of chemicals for those capable of attacking new targets in the AIDS virus. Two potential targets, the viral proteins known as Vif and ribonuclease H (RNase H), play essential roles in the replication of HIV, but have not as yet been studied as potential targets for new drugs. Grants were awarded to two scientists to study these proteins in June 2001, when amfAR began funding combinatorial library research.
The latest grant cycle also includes $1.3 million for basic research projects to design a safe and effective AIDS vaccine, develop methods of restoring immune system function in people living with HIV/AIDS, and discover topical microbicides that could prevent the sexual transmission of HIV.
amfAR was an early funder of AIDS vaccine research and produced one of the most promising breakthroughs in the field—genetic immunization, or DNA vaccines. Scientists at Merck Research Laboratories recently reported that two DNA vaccine candidates have shown promising capability in eliciting immune responses. The concept behind Merck’s vaccine candidates—genetic immunization—was first funded by amfAR through a basic research grant to Dr. Stephen Johnston of the University of Texas Southwestern Medical Center in Dallas. His amfAR-funded research, conducted in 1992 and subsequently reported in Nature in 1995, was the first to demonstrate that DNA vaccines could stimulate a strong immune response in animals, and galvanized the field of genetic immunization in the ensuing years. The Merck results are widely seen as the strongest evidence thus far for the efficacy of a genetically-engineered vaccine. Most experts agree that a safe, effective, and affordable vaccine is crucial to preventing the pandemic’s further spread.
While highly active antiretroviral therapy (HAART) often succeeds in suppressing the virus, HIV-infected patients do not recover full immune function, and some remain susceptible to opportunistic infections, cancers, and other illnesses. In fact, as people with HIV/AIDS live longer with impaired immune systems, many are encountering a variety of unique health problems. The Foundation continues to fund a targeted grant initiative to explore the nature of immune deficiency and identify novel methods of stimulating the immune system’s ability to fight HIV and other infectious agents. In combination with highly effective antiretroviral therapy, such methods could eventually constitute a clinical cure for AIDS.
Microbicides are synthetic or natural substances that could be applied topically prior to sexual intercourse in order to neutralize HIV and prevent other sexually transmitted diseases that can facilitate HIV infection. With 95 percent of all HIV infections due to sexual contact, an effective microbicide could save millions of lives, especially among women in developing countries, who often lack the power to avoid sex with partners who may be HIV-infected or to insist on condom use. Unlike other barrier methods, microbicides could be used without the cooperation or knowledge of one’s sexual partner. To date, the Foundation has awarded roughly $1.5 million for microbicide research.
amfAR's March 2002 grant awards also include over $1 million for two-year fellowships that enable investigators new to the AIDS field to conduct original research under the guidance of experienced scientific sponsors.
Both amfAR grantees and fellows are selected through a rigorous process of peer review conducted by members of amfAR’s Scientific Advisory Committee, a large group of highly qualified professionals who volunteer their time and expertise to evaluate proposals on the basis of scientific merit, relevance and promise.
See the sidebar to link to a press release that includes a complete listing of grantees, grant amounts, and brief descriptions of individual research projects.