Monday 10 March 2014

Long-acting HIV drug shows promise

Two new sets of research show that regular injections of an antiretroviral drug protects macaques monkeys from simian-human immunodeficiency virus infection. The research has raised hopes that preventing HIV infection in humans will soon be as easy as a shot in the arm four times a year. Researchers are optimistic that the findings could one day lead to a new generation of HIV drugs for infected people.

The medication has been developed by researchers from Rockefeller University, GlaxoSmithKline, and the Tulane National Primate Research Center. The new drug is termed a "integrase strand-transfer inhibitor GSK744", and it has been developed as a long-acting injectable, designed to be administered every three months.

GSK744 (also known as S/GSK1265744) is an investigational new drug under development for the treatment of HIV infection. Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Integrase inhibitors were initially developed for the treatment of HIV infection, but they could also be applied to other retroviruses. GSK744 works by interfering with the enzyme that HIV uses to insert its DNA into the human genome. This blocks the key step needed for the AIDS virus to replicate itself, and the viral DNA simply degrades inside the cell.

In investigational studies, the GSK744 agent has been packaged into nanoparticles (GSK744LAP) conferring an exceptionally long half-life of 21–50 days following a single dose. In theory, this would make possible suppression of HIV with dosing as infrequently as once every three months. Animal studies indicate that this theory is getting closer to reality.

Based on a report in the journal Science, the drug has led to monkeys, infected with a virus very similar to HIV called simian-human immunodeficiency virus (SHIV), becoming protected. The study, by Chasity Andrews and colleagues is titled " Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus".

For the study, Andrews and her colleagues studied sixteen rhesus macaques. The monkeys were challenged with SHIV. After this,  eight monkeys received placebo and eight were administered with GSK744 (where the drug was injected intramuscularly). All eight macaques who received GSK744 remained averimic (that means without SHIV), during both the rectal challenge phase and during the subsequent follow-up ten-week examination phase. In contrast, all eight macques who received placebo were infected with SHIV during the challenge phase.

For the next phase of the study, the researchers aim to carry out similar tests where they will determine the minimum protective dose of GSK744 that is required in order to stop SHIV from replicating and multiplying.

Remarkably, a second research team from the U.S. Centers for Disease Control and Prevention (CDC) have found a similar effect when studying GSK744 in female monkeys.

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With the new HIV research findings, both research groups have presented their results to the U.S. Centers for Disease Control and Prevention (CDC) annual Conference on Retroviruses and Opportunistic Infections, which held in Boston this week.

Commenting on the research findings, The New York Times explains: “If the findings can be replicated in humans, they have the potential to overcome a major problem in AIDS prevention: that many people fail to take their antiretroviral pills regularly."

In short, this could be the first step towards an HIV vaccine. In the meantime, ‘pre-exposure prophylaxis’ with drugs used to treat the infection has become one of the most promising strategies to cut down HIV infection rates among high-risk populations. On this basis the newly developed drug for monkeys could, within a short space of time, be turned into a long-acting injectable drug for people and one that could improve upon current treatments. Furthermore, since integrase inhibitors target a distinct step in the retroviral life cycle, they may be taken in combination with other types of HIV drugs to minimize adaptation by the virus. They are also useful in salvage therapy for patients whose virus has mutated and acquired resistance to other drugs.

The main obstacle for realizing a version effective against HIV is likely to be keeping up the treatment regime.  Philip Johnson of the Children’s Hospital of Philadelphia in Pennsylvania told the science site Science Now. “This is going to require multiple injections over the lifetime of an individual,” he said, asking: “How feasible is it truly in the long term?”

Much more likely it seems that having to make multiple pills each day for HIV. GSK744 injections have the potential to overcome a major problem in AIDS prevention: that many people fail to take their antiretroviral pills regularly.

Posted by Tim Sandle

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