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Studies Change Common Theories on AIDS

New Views on Link Between HIV and Immune System May Lead to Cure

Drs. Ho and Shaw realized that they had a unique opportunity to use powerful drugs to watch the infection in progress by essentially creating a snapshot.

Each team administered the drugs to HIV patients with low T4 cell counts, causing a significant decrease in virus population. The drugs used by the researchers inhibit reverse transcriptase or protease, two enzymes essential to virus reproduction.

Both teams found that within two weeks, all of the AIDS virus in the body were mutated to resist the drug. From this, the researchers were able to calculate that 100 million to one billion new virus particles are produced every day.

When the investigators stopped giving the drug, the body kept producing T cells at high levels, allowing the researchers to calculate that about one billion new T cells were being generated every day.

New Medical Approach

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Researchers have long worked to figure out ways to boost the immune system to fight the virus, but Shaw thinks that their results signal researchers to change that approach and others.

"There should be a greater emphasis on drugs that inhibit viral replication," Shaw said. "We can also design shorter trials to test more therapies."

"There are [currently] more than 10 potentially valid therapeutic agents, but each has to be optimized in dosage, at what stage of infection it is first given, and whether it is effective combined with other drugs," Shaw said. "Right now, it can take years to test just two or three drugs whereas [we believe] one can explore the potential in just one or two months."

Shaw's group actually measured the rate of appearance of mutants for one drug, nevirapine, which inhibits reverse transcriptase.

"The population of virus mutants replaces sensitive virus in as little as 14 to 28 days," Shaw said.

In an accompanying editorial, Simon Wain-Hobson of the Pasteur Institute in Paris compares the battle between virus and immune system to life in the city.

"That billions of virions and infected cells can be destroyed every day vividly illustrates the very hostile environment created by the immune system--the meanest of streets are nothing by comparison," Wain-Hobson wrote.

Wain-Hobson also believes the research dictates that anti-HIV drugs should be given to patients earlier in their infection, continuing throughout the infection.

Shaw sees this work as "the first step in what needs to be a series of studies." He believes that HIV and CD4 need to be correlated at all stages of infection, new drugs must be made to combat existing and new enzyme targets, and combinations of drugs must be tested.

"Combinations may cause enhancement of therapy," Shaw said. "One drug may cause the virus to mutate so that it becomes more susceptible to another drug."

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