LONDON- The AIDS virus mounts an aggressive attack on the human immune system from the moment it enters the bloodstream according to several new studies. The new data is changing the way researchers look at HIV infection and AIDS pathogenesis.

Until recently, the consensus among AIDS researchers has been that AIDS represents a chronic infection process maintained by chronically infected virus-shedding T-cells. Research has concentrated on the later stages of infection when once dormant virus producing cells are activated. Whereas T-cell infection was initially the focus of efforts to describe the dynamics of HIV infection, researchers now believe HIV infection of the lymphatic system is at least as important in giving the virus a foothold.

While HIV does follow a chronic course, the latest research suggests HIV gets right to work from the moment of infection. HIV invades susceptible cells which immediately begin producing more than 100 million new viral particles per day. The body tries to replenish cells depleted by HIV, but is stymied by immune system cells which target the bodies own cells hiding the virus.

This means that AIDS infection does not result from a weak immune system, rather the immune system exhausts itself in the effort to rid itself of HIV. Recent observations suggest HIV infection is a highly dynamic process characterized by constant new rounds of HIV infection, according to Dr. George M. Shaw and colleagues at the University of Alabama.

Dr. Shaw and his team observed the aggressive behavior of HIV during clinical trials with three new potential AIDS drugs, one an inhibitor of the reverse transcriptase enzyme required by HIV to replicate, the other two inhibitors of protease, an enzyme used by HIV to make its envelope protein coating.

All three of the drugs showed powerful effects, reducing the amount of virus and the number of virus producing cells by half in only two days. All three of the drugs work by preventing new infection of cells. Unfortunately, new HIV strains resistant to the drugs evolved in less than four weeks.

Little has been known about the dynamics of HIV replication in the human host. This is partly because early antiretroviral agents did not slow viral replication sufficiently, and because existing laboratory methods could not quantify the virus and its mutations.

Dr. Shaw and colleagues were able to overcome both of these obstacles. The new drugs are able to interfere significantly with viral replication, and new quantitative laboratory methods (including in situ PCR and hybridization methods) allow measurement of viral RNA in the blood and of changes in viral genotype and phenotype. These laboratory techniques revealed both an explosive turnover of new virus and ongoing viral evolution leading to drug resistant mutations. It was also shown that the virus quickly dominated the immune system, even after more than 99% of it had been eliminated by drug therapy.

In a related study, noted AIDS researcher Dr. David Ho of the Aaron Diamond Research Center at New York University, came to similar conclusions while testing yet another experimental AIDS drug. His study also showed that HIV replication is rapid and continuous, leading to rapid turnover of CD4 T-Cells.

This rapid CD4 cell turnover has important implications, notes Dr. Ho. He compared the CD4 depletion seen in advanced HIV infection with a sink containing a small amount of water, with the tap and drain both wide open. Since the immune system cannot regenerate fast enough, the sink eventually drains. The best way to reverse the immunodeficiency associated with HIV infection might then be to concentrate on plugging the drain by developing way to control virally mediated cell destruction, rather than emphasizing T-cell reconstitution, which he likened to putting in a second tap.

The new information should lead to a more rational approach to developing AIDS treatments and vaccines. New efforts to bolster the immune response while weakening HIV at the same time could allow the bodies natural defenses to overwhelm the viral invader. The new findings also suggest treatment, probably with multiple drug regimens, will have be begin as soon as possible after infection.

Both studies appeared recently in Nature. See Shaw et al. and Ho et al, Nature, 1/12/95, v.373.

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