Three pronged attack
researchers , politicians and patient-activists traded progress reports about the deadly spread of the human immunodeficiency virus ( hiv ) at the 11th international conference on aids recently. Twenty-two million people live with aids today, and five new victims are infected every minute.
New drug combinations that have beaten the virus to undetectable amounts in most patients for a year have got the top billing. According to David D Ho of the Aaron Diamond aids R esearch Centre ( adarc ) in New York, the amount of virus in a patient's plasma, as detected by viral rna, indicates how many of the patient's cells are infected and thus "the fire that burns up the immune system'.
The resistant mutant forms that spread throughout patients within mere weeks is the problem that is being faced by most of the anti- hiv drugs. The mutant gains the advantage due to the extremely high turnover of viruses. Recent numbers show that even in early stages of hiv infection, a patient produces 10 billion particles a day, including millions of mutants. There is no single drug that can win the battle although combinations can slow replication of the virus.
A study of a combination of three drugs, azt, 3tc and indinavir is being tried by Roy M Gulick of New York University Medical Center and his colleagues. azt and 3tc inhibit hiv 's reverse transcriptase, the enzyme hiv uses when it first infects a cell. Indinavir's target is the hiv protease, which the virus needs later to assemble new particles. Some other combinations have also shown positive results.
Researchers now believe that physicians should avoid using any single antiviral medicine, because it encourages the evolution of resistant mutants. "If you leave the door half open, the virus will push it open the rest of the way,' says Emilio A Emini of Merck.
Combination therapy has shown a ray of hope that hiv can be eliminated from patients. According to Ho's calculations if viral replication could be suppressed for one to three years the significant pools of hiv in the body infection could be conquered. Ho is testing a group of patients with a protease inhibitor called ritonavir, together with azt and 3 tc.
H o has focussed his study around newly infected patients, because they have had less time to accumulate mutations and have healthier immune systems. If the patients have no signs of virus in their lymph nodes after a year, the therapy will be stopped. Even if the virus returns studies suggest that its intensity will be less than that it would have been without the therapy. No one can be sure triple or quadruple drug therapies can supress hiv . Moreover, some patients maybe unable to tolerate the side effects.
Cost of the drugs is another practical problem. A triple therapy regimen costs more than $10,000 a year. A whooping sum like this is completely out of reach for patients or governments of the developing world, where 94 per cent of hiv infections occur.
William E Paul, head of the office of aids research at the National Institutes of Health complains that efforts to design vaccines do not adequately exploit all the recent advances in biotechnology or the approaches suggested by our greater understanding of the immune system. But afraid of being held liable if a vaccine is ineffective or causes harm pharmaceutical companies are not venturing into this area.
John Moore of adarc says that by simply inactivating live hiv a vaccine that is effective to a certain degree can be made now. Although the strategy is risky, some developing countries might see that as a risk worth taking, Moore says.