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New HIV Drugs and Better Ways to Use the Old Ones

February 2002

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Not long ago, there were few drugs to fight HIV and we did not know how to use them. Today, there are 18 FDA approved antiretrovirals which we are learning how to use, and at least 25 new HIV drugs in the development pipeline, as well as a half dozen new treatment methods.


Recently Approved by the FDA

There has been steady progress in developing new drugs that are not cross resistant to existing drugs, which are stronger than existing drugs, easier to take, with simplified dosing schedules and fewer side effects.

Viread (the generic name is tenofovir), made by Gilead, is showing resilience in fighting HIV in people who have used up many drugs, getting 75% reductions in viral load. Viread has had few problems with side effects and is a once-a-day drug.


Drugs in the Pipeline and How They Get Out

There are a series of steps in the development of a new drug for HIV.

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The first step is basic research that gives ideas, clues and examples to scientists on how the virus might be fought with some therapy or drug.

The next step is to see if there is evidence the drug works against HIV in the test tube, and in animals that have a similar virus.

The next steps involve testing the drug in people and these experiments are usually done in three phases. Phase I is testing the drug for safety. Phase II is seeing if there is any benefit while looking for more subtle side effects. Phase III is testing the drug in enough people long enough to prove it works. The FDA can license a drug after this and in theory is supposed to be tested further for long term side effects, and how to better use it.

There are many HIV drugs in development that look like they might help us in powerful ways, at least 25 in phase I, II or III trials.

In Phase III Trials

(almost all the way through the drug pipeline)

Emtricitabine (FTC) made by Triangle Pharmaceuticals. It is a nuke that is closely related to Epivir (3TC) that unfortunately is probably not useful for people who have virus resistant to 3TC. FTC needs to be taken only once a day, has few side effects, may have a good long term side effect profile, looks quite a bit stronger than 3TC, and people who are taking 3TC in successful regimens might be able to switch to FTC and benefit from the once-a-day dosing of the drug as well as the increased strength of the drug.

Pentafuside (T-20) made by Trimeris with the help of Roche, is an exciting recent drug development. T-20 stops HIV from getting inside a cell. It is the first "fusion" inhibitor, and appears quite powerful. It will work on people whose virus is resistant to existing types of drugs, but it won't work alone. Used alone, HIV gets resistant to it rapidly. You need a good combination of drugs to use with it to prevent resistance. Hopefully, used with other new drugs that stop HIV from getting into a cell, (all in early stages of development) this kind of drug could be part of a new, different drug combination that works when all other drugs fail.

In Phase II/III Trials

(trials large enough so that their data could be used toward licensing the drug)

VX-175/GSK433908 (nice name!) This drug from Vertex and Glaxo is a protease inhibitor identical to Amprenavir (agenerase) except it has a lot fewer pills and it can be taken once a day combined with ritonavir. It seems to retain some level of activity against virus that is resistant to Kaletra, and other protease inhibitors, and would likely not have the cholesterol elevating problems of many earlier protease inhibitors.

Atazanavir (brand named Zrivada and formerly called BMS-232623) This drug from Bristol-Myers Squibb (BMS) is a protease inhibitor that looks like it might not have the problem of causing blood levels of lipids to be high. In a study done with Atazanavir plus Saquinavir, trigliceride levels actually decreased by 25%! It is taken only once a day, and seems to have very few side effects compared with the earlier inhibitors. The once-a-day formulation makes it possible, given the likelihood of once-a-day indications for other drugs like Zerit (d4T), Epivir (3TC), Sustiva (efavirenz), and Viramune (nevirapine) to talk seriously about a once-a-day drug regimens.

Hydroxyurea This cancer drug, being looked at for use in HIV, is being studied by BMS. It appears to be useful in increasing the strength of Videx (ddI). It, however, has had a reputation for problematic side effects.

Phase II Trials

(these trials are large enough to determine if there is any effect on HIV and can find more subtle side effects that may not show up in smaller, shorter phase I trials)

Carpravirine This drug of Agouron's (now Pfizer) is a NNRTI which has had some trouble in animal toxicity studies but which looks pretty powerful. It may be able to fight HIV resistant to other drugs of this class.

TMC120 and 125 These drugs are both NNRTIs being developed by Tibotec. They appear powerful and not cross resistant to the other drugs in this class.

Calanolide A is a NNRTI being developed by Sarawak Medichem. It appears totally different from the other NNRTIs, may be synergistic with them, and has a different resistance profile from the NNRTIs presently available. This means it is possible that this new drug will work on people who have used other NNRTIs and now have virus resistant to them. It comes from a tree in the tropical rain forest of Malaysia, the 'Calophyllum laniferum', and was first discovered by the National Cancer Institute. The NCI owns the drug, the Malaysian Government is helping to develop the drug and Malaysia will benefit from any profits.

Soon to Enter the Pipeline

This next category includes drugs that will fight resistant virus.

Tripanavir is a protease inhibitor being developed by Boehringer Ingelheim that appears to be work in patients whose virus has grown resistant to most protease inhibitors.

An 'attachment' inhibitor called PRO 542 and an 'entry' inhibitor both being developed by Progenics. These drugs stop HIV before it gets into a cell. They may be synergistic with T-20, and if this is so, may create a new kind of "cocktail" that would work on virus resistant to all the presently available classes of drugs.

Another drug soon to be tested is an integrase inhibitor, S1360, originally being developed by Shionogi Pharmaceuticals and recently purchased by Glaxo.

There is a second generation fusion inhibitor of Trimeris called T21246 that will work on virus that is resistant to the first one they developed called T-20, two next generation NNRTIs being developed by BMS that will fight virus resistant to Sustiva, an interesting new nuke called DAPD being developed by Triangle Pharmaceuticals, a new kind of drug called DEHSPM which inhibits hypusin/eIF-5A -- it may stop the virus from replicating, and finally, a zinc finger hitter being attempted by a firm in Belgium, Hubriphar.


New Ways to Use Old Drugs

In addition to the new drugs, there are updates about new ways to use old drugs that are being tested out around the world.
  • Dr. Mark Dybul's work at the NIH is looking at the safety of taking drug cocktails every other week.
  • Dr. Bruce Walker of Massachusetts General Hospital is trying out two ideas -- treating people within a few days or weeks of infection. This appears to protect the immune system and may allow people to stop using antivirals for long periods of time. Secondly, seeing if using vaccines, such as Remune and the Merck DNA vaccine can help the body keep down virus without the help of drugs.
  • Finally, there are trials going on to see if boosting protease inhibitors leads to a more powerful, durable regimen. We now know using a small amount of Ritonavir with other protease inhibitors makes it possible to have twice-a-day regimens more powerful than any using only one protease inhibitor. And there are trials using Kaletra (lopinavir) with Fortovase (saquinavir) to see if this very powerful drug can be made even more powerful.


Diagnostic Tests

The use of resistance assays is still in development, but a new tool developed by Virologic, the Phenosense GT assay, allows us to look at BOTH genotypic and phenotypic assays and get a better guess at what drugs will work on someone and which won't.


Helping With Side Effects

Finally, there are ongoing efforts to deal with side effects directly such as the use of Human Growth Hormone (Serostim) made by Serono and 'New Fill' for facial wasting. There's Procrit (made by Ortho Biotech) for anemia.


The Future

The future will focus on four goals: finding a cure, learning how to use the medicines we have in more efficient ways, developing drugs that are easier to take and are easier on the body as well as developing the political will to share these miracle drugs with the millions around the world that desperately need them.

David Scondras is the founder and chairman of Search For A Cure. Scondras developed the nationally recognized HIV treatment series, Reasons for Hope. All articles in the series are reviewed by expert HIV doctors and scientists and an HIV positive and negative focus group to ensure both accuracy and understandability. This article was reviewed by Howard Grossman, M.D., Assistant Clinical Professor of Medicine, Columbia University College of Physicians and Surgeons Associate, Attending Physician, St. Luke's-Roosevelt Hospital, NY, NY.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!



  
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This article was provided by Search for a Cure. It is a part of the publication Reasons for Hope.
 
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