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Dr David D Ho
by Tan Lay Leng

R David D Ho, Scientific Director and CEO of the Aaron Diamonds AIDS Research Center in New York City, enjoys worldwide renown for his "cocktail" or combination-drug therapy for AIDS. The treatment has proven effective in lowering the death rate of those afflicted with the disease and represents the de rigueur regimen in developed countries.

His pioneering work in the field of HIV/AIDS has earned him international recognition as well as a place on the cover of Time magazine as its Man of the Year in 1996.

The Rockefeller University professor visited Singapore recently to deliver a public lecture during the International Conference on Fundamental Sciences: Biological and Chemical Sciences, organised by the National University of Singapore and the University of Toronto, Canada.

During his lecture entitled "The HIV/AIDS Epidemic and Scientific Advances", Ho talks about the advances in AIDS research in terms of understanding HIV and therapeutic options.

He paints a grim picture of the HIV/AIDS epidemic worldwide. The disease has already claimed 18 million lives, and 36 million live with the virus that is slowly destroying their immune systems. The lethal microbe was responsible for over 3 million deaths last year and 5 million new infections. The situation has grown especially critical in Africa, where AIDS spreads at an alarming rate and has infected more than 10% of the population.

In Asia, the HIV/AIDS epidemic seems to be at an earlier stage as compared with the rest of the world. However, Asia's huge population is at risk, emerging statistics suggest. The World Health Organisation estimates that India has about 4 million HIV-infected people. In China, more than 500,000 people are infected, half of them intravenous drug users in Yunnan, near the Myanmar border.

Despite the dismal scenario, Ho sees hope yet for the sufferers of the dreaded disease. He stresses that with proper medical attention, a positive diagnosis of HIV or AIDS no longer spells a death sentence. HIV could be placed under reasonable control with the crop of new drugs developed in the US and Europe, 15 at the last count. These reverse transcriptase inhibitors and protease inhibitors produce better results with early detection and treatment of the virus.

The most prevalent strain of HIV is HIV type 1. Because of its high mutation rate of about 1 in 10,000, and according to the Darwinian theory of evolution that propounds the survival of the fittest, the virus has become increasingly resistant to earlier forms of treatment. It is now quite impossible to counter the pathogen with a single drug. Thus when Ho adopted the combination-drug-therapy approach, it produced unprecedented results of breakthrough proportions.

The combination treatment has had a dramatic impact on AIDS mortality in developed countries. Today, the death rate has dropped to one-seventh of that just five years ago. Prior to the combination-therapy era, immunotherapy or treatment by stimulating the body's own immune system had failed miserably, Ho notes.

Despite the availability of drugs to control HIV, about 95% of AIDS patients, most of them from developing countries, do not have access to treatment. This is attributed to the high cost of medication, typically around US$12,000 annually per person, and constraints in delivering the drugs to those afflicted with the disease in these countries. Therefore, Ho sees that the only hope for the future lies in the development of an AIDS vaccine.

During a recent interview with the Singapore press, Ho gives an update of ongoing HIV/AIDS research. Stepped-up efforts in vaccine research were launched in the US several years ago under a presidential directive. Former US President Bill Clinton declared that he felt confident that a vaccine for AIDS would be available by 2007.

"It's a reasonable projection, but nobody knows for sure," Ho says. Despite declining to speculate on when a vaccine will be ready, he expresses optimism at the amount of promising data emerging from experimental studies in animals. "This doesn't mean a vaccine is around the corner - it's going to take a lot of work; there's a long road ahead of us," he cautions.

Ho's research group has been trying to develop a vaccine that could be tested in Asia, particularly for a strain of HIV known as HIV subtype C, quite prevalent in southern Africa, India, and southern China. He reveals that his team has almost completed work on a DNA vaccine and will start clinical testing in the US next year.

DNA vaccine involves the insertion of HIV genes into a small, circular piece of DNA called plasmid, which is then injected into the muscle of the host. Certain cells in the body will take up the plasmid and express the HIV genes. The HIV protein will cause the body's immune system to respond and produce killer T-cells to attack HIV-infected cells.

DNA vaccine will be a more effective way of destroying HIV than a traditional vaccine, Ho asserts. After testing and getting approval from the US Food and Drug Administration, he says, the vaccine could be exported to other parts of the world such as China and India. His group has signed an agreement with the Chinese Academy of Preventive Medicine to collaborate on AIDS research and perform clinical trials in China.

"In general, we are trying to find out how the immune system can better control HIV. We do know that for most people who are infected, the immune system ultimately loses to the virus. If untreated, this is a deadly infection. Some of our therapeutic strategies utilise not only drugs but also other things that we hope could help boost the immune system," he says.

Alternative Therapy

Ho thinks the possibility of treating HIV/AIDS using an alternative form of therapy may exist, but so far herbal and traditional medicine have not been found "that would meet the scientific criteria for proven therapy."

Another area of research in Ho's laboratory is the pathogenesis of HIV infection with particular emphasis on the dynamics of HIV replication in vivo. His team also devotes considerable effort to developing and testing treatment strategies that emerge from new understanding of viral dynamics.

Although confident that a protective AIDS vaccine would be available in the coming years, Ho cautions that the eventual control of AIDS would require the collective political will of world leaders to acknowledge the enormity of this disease and to commit the necessary resources to stop the scourge. He sees the need to mount educational campaigns and mobilise preventive measures, in addition to working with the scientific community to come up with new vaccines.

Delivering the drug to the needy in developing countries constitutes another big issue that will not be easily resolved, he foresees. The United Nations is trying to do its part by getting the richer nations to donate to a global fund for developing countries to gain access to medication and treatment.

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