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The AIDS Drug Pipeline

New Nukes

Nucleoside RT inhibitors -- NRTIs or "nukes" in the lingo of HIV research -- have been the mainstay of AIDS therapy since AZT came out in 1987. The "RT" in NRTI is the target -- it's the tool the virus uses to change its RNA genetic code into the DNA code that takes over a cell. Seven now are approved, including Viread, a close relative to the NRTI family.

What's new in nukes:

  • DPC 817 kills HIV that's already developed resistance to AZT (Retrovir) and lamivudine. It's in early human trials.
  • BCH-13520 kills HIV resistant to other nukes. In the test tube, HIV has a hard time getting around this drug. Animal tests are underway.
  • GS 7340 is a form of Viread designed to work better as an oral drug. It looks good in animal studies.

New Non-Nukes

Non-nucleoside RT inhibitors -- NNRTIs or non-nukes -- attack the same target as nukes, but in a different way. One of these drugs, Sustiva, is among the most potent anti-HIV drugs ever seen. The search is on for equally powerful drugs without as many side effects. New non-nukes include:

TMC125 is so potent that all by itself it works as quickly as an extremely powerful five-drug combination. Human trials show that it works against HIV that's resistant to other non-nukes.

DPC 083 promises to be even stronger than Sustiva with fewer side effects. Human tests continue.

Integrase Inhibitors

Integrase inhibitors target yet another crucial HIV target. Integrase is the sewing kit HIV uses to splice its own DNA into the DNA of a cell. There aren't yet any approved integrase inhibitors -- but that could change:

  • S-1360 is a new drug already in human tests. It's worked very well in animal studies.
  • Merck has an as-yet-unnamed integrase inhibitor ready for human tests, according to The Wall Street Journal.

Protease Inhibitors

Protease inhibitors -- PIs -- blunt the scissors HIV uses to cut newly made pieces of virus into the right shapes. The newest of these drugs, Kaletra, gained approval in 2000. Studies presented at the Retrovirus conference show that Kaletra can be taken in once-a-day doses.

New Ideas

Researchers are working on new ways to skin the HIV cat:

  • A class of drugs with a jaw-breaking name -- metalloporphyrins -- attacks the HIV RT target in an entirely new way. Their properties seem just right for a human drug, but studies are still in the test-tube stage.
  • A creation called double-stranded RNA (dsRNA) is a smart bomb. It's just two strands of RNA twined together. Once inside a cell, it seeks out and destroys any RNA that looks like one of its strands. Since HIV is an RNA virus, this plan would seem to have obvious advantages. It's still in test-tube studies.


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