Successes, failures mark 30 years of HIV/AIDS research (page 2)

Failures and new opportunities

Even when covering science, the mainstream media tend to deal in absolutes--even though we know that an emerging science does not necessarily work in absolutes. One study builds on another, which builds on another until--sometimes over a period of decades--a clear picture emerges. But the media can be forgiven a "pass/fail" rating system when science reaches the point where actual potential blockbuster products, like AIDS vaccines, are tested. It either passes or it fails, and there does not appear to be much nuance there. And add to the fact that the company trying out its vaccine is publicly traded, and the financial press steps in to frame a drug trial as a horse race, either a victory or defeat for the company, with accompanying ups and downs in stock prices.

This is what happened to Merck back in 2007, when failure of its STEP HIV vaccine in Phase IIb trials forced the drug giant to scrap the vaccine program altogether. The multinational, 3,000-patient Phase trial tested a Merck HIV-1 subtype B vaccine known as MRKAd5. It was designed to make the body produce white blood cells that could recognize and target specific parts of HIV-1 known as Gag, Pol and Nef. Preliminary tests indicated the vaccine was encouraging the appearance of the desired virus-attacking cells. However, immunizations were halted after the first interim analysis indicated that the vaccine neither prevented HIV-1 infection nor reduced the load of virus in the body.

End of story, right? Not quite.

Now, James Mullins, University of Washington professor of microbiology, and his a team have analyzed the genome sequences in HIV-1 isolated from 68 newly infected volunteers in the STEP trial. The research team tested for a "sieve effect," which, Mullins explains, occurs when a vaccine successfully blocks some strains of virus and not others.

This is the first evidence that vaccine-induced cellular immune responses against HIV-1 infection exert selective pressure on the virus. "Selective pressure" refers to environmental demands that favor certain genetic traits over others. The researchers added that their findings suggest that new vaccines should be designed to put selective pressure on the virus in a controlled manner.

This is the way science really works. Old failures lead to new avenues of inquiry.

Combination Antiretrovirals

Thankfully, one thing that has changed in 30 years of dealing with the AIDS virus is that a diagnosis is no longer an immediate death sentence. Well, that is, for those who can afford the treatment. As with the search for a vaccine, medication to treat HIV infection needs to stay one step ahead of the virus's ability to quickly adapt and evolve.

For a while, these came in the form of cocktails of hard-to-pronounce names like zidovudine, lamivudine, abacavir, emtricitabine and others. More recently, drug companies have combined these complex cocktails into simpler, fixed-dose combination antiretroviral drugs.

The biggest selling of all the combination HIV retrovirals is Truvada, by Gilead. Others are Atripla, produced by Gilead and Bristol-Myers Squibb, Combivir by GlaxoSmithKline and Kaletra by Abbott Laboratories.

While antiretroviral combination meds have revolutionized care of HIV-positive patients, they do come with many drawbacks. The drugs can have serious side effects, the virus can build resistance to them if the patient misses doses, and they are so expensive that the majority of the world's infected population can't afford treatment.

Antiretroviral drugs as prevention

For decades, the only known preventative has been either abstinence or use of condoms. Now, that may be changing as antiretroviral combination drugs are being tested for their preventative power. Indeed, many--like Truvada--are already being prescribed off-label for prevention, despite reluctance of many doctors to prescribe such an expensive drug.

A recent study showed that Truvada prevented high-risk patients from contracting the virus 44 percent of the time, although a subsequent study showed that the drug failed to produce the same kinds of results for women.

Still, the World Health Organization is encouraging on this issue, and AIDS activists appear to be excited about it. More studies are underway.

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Successes, failures mark 30 years of HIV/AIDS research (page 2)

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