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Researchers Present Early Data On New Treatment Approaches And Drugs For HIV (AIDS 2010)

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Published: Jul 22, 2010 1:30 pm
Researchers Present Early Data On New Treatment Approaches And Drugs For HIV (AIDS 2010)

Several innovative but preliminary treatment approaches were presented Monday at the 2010 International AIDS Conference currently underway in Vienna, Austria. Presentations included the results of animal and laboratory studies on novel drugs and new generations of traditional therapies.

Two of the studies focused on methods to completely eliminate HIV from the body. More specifically, they targeted latent HIV – HIV that lies dormant in infected cells and can start multiplying again if antiretroviral therapy is stopped.

Latent HIV is difficult to get rid of because after infection, the virus actually inserts its own DNA into a cell’s normal DNA sequence. Antiretrovirals can prevent the virus from using this DNA to make more of itself, but they can’t remove the virus DNA once it has been inserted.

As a result, HIV can hide out in an infected person’s DNA indefinitely, even if they are taking antiretrovirals. This type of HIV is called latent HIV and is the reason HIV cannot be cured with current treatments.

Two new studies presented Monday focused on targeting and removing latent HIV. In both studies, researchers created treatments that were shown in animal tests to reduce the amount of latent HIV in the body. In one case, however, the results were only temporary.

Three other studies showed positive preliminary results for new antiretroviral drugs: four new protease inhibitors, and two new integrase inhibitors. The new drugs show promise, but are still in early stages of development.

New Treatments To Remove Latent HIV From Cells

Two studies were presented showing preliminary research on new treatments to remove latent HIV from cells.

In the first study, a team of German and Swiss researchers created an artificial protein that cuts latent HIV DNA out of cells and prevents virus replication in mice.

Unlike normal antiretrovirals, the new protein is able to find virus DNA inside a cell’s DNA and cut it out of the sequence. It can also act like a regular antiretroviral and prevent the virus from multiplying.

In this study, the investigators modified either human adult CD4 (white blood) cells or human blood stem cells so that they could produce the artificial protein. They then transplanted these cells into mice to see if the protein would effectively remove latent HIV DNA or have antiretroviral activity.

The researchers found that the protein caused a substantial decrease in HIV viral loads (amount of HIV in the blood) and also protected CD4 cells in the mice, with no toxicity.

As a result of these promising results, the scientists recommend further study of the protein to see if it could be used as a novel treatment for HIV in addition to traditional antiretrovirals.

In the second study, Italian and American researchers looked at Gar1041, an experimental leukemia drug, in combination with antiretroviral therapy to see if it could reduce the amount of latent HIV DNA in monkey cells.

GAR1041 is a new type of experimental drug called an epigenetic drug. Epigenetic drugs are used to turn genes on and off and have mostly been studied in cancer cells. However, the researchers thought they might also be useful to fight latent HIV.

Within one month of treatment with Gar1041 plus antiretroviral drugs, the researchers found that the amount of latent HIV in the monkeys significantly decreased. The drop was not observed in monkeys receiving only antiretroviral therapy.

However, the concentrations of latent HIV rebounded after two months of therapy. The researchers concluded that their study shows latent HIV can be reduced using drug treatments, which is promising. However, further research would be necessary to permanently reduce latent HIV and keep it from rebounding.

Improved Therapies: Novel Protease And Integrase Inhibitors

A joint effort between Japanese and American scientists yielded four new protease inhibitors that were highly effective against drug-resistant HIV in laboratory tests.

Protease inhibitors, such as Kaletra (lopinavir/ritonavir) or Prezista (darunavir), work by blocking a virus protein called protease, which then prevents virus proteins from assembling properly.

The four new drugs developed by the Japanese-American team were found to be highly effective protease inhibitors in the laboratory. One of the drugs was more powerful than Prezista. As a result, they will be studied further as potential drugs to fight resistant HIV strains.

Another study, presented by researchers at GlaxoSmithKline, showed results for a potential new integrase inhibitor.

Integrase inhibitors are a relatively new class of drugs. They work by blocking the protein the virus uses to insert its DNA into the DNA of a healthy cell, thus preventing HIV from replicating.

In 2007, Isentress (raltegravir) was the first integrase inhibitor to receive approval from the United States Food and Drug Administration. Soon after its introduction, HIV resistance against Isentress developed.

The new integrase inhibitor, S/GSK1265744, was effective in laboratory tests against HIV virus isolated from patients showing resistance to Isentress. As a result, it could be used to treat HIV that is resistant to Isentress.

Finally, in another study, Belgian and Swiss scientists presented a new type of integrase inhibitor called LEDGINs. LEDGINs work slightly differently than Isentress and were very effective in the laboratory against Isentress-resistant HIV.

Although still in the early stages of development, the drugs show promise as new treatments for HIV. Further studies to assess their effectiveness are currently underway.

For more information, please see the AIDS 2010 conference website.

Photo by kaibara87 on Flickr – some rights reserved.
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