On The Horizon: The Next Generation of HIV Medications

Soon we will have better versions of the drugs we use to stop HIV. These drugs will fight resistant virus, have fewer side effects, and be easier to take.

Once a Day!

There is a new protease inhibitor being made by Bristol Myers Squibb (BMS) that looks like it can be used once a day. For now it is called BMS232632. It seems at least twice as strong as any other protease inhibitor, and seems able to get viral load down in people whose virus is resistant three protease inhibitors. It has kept virus to undetectable in people who take it once a day for 48 weeks so far! Also, there has been no evidence yet of any increase in total cholesterol or triglycerides. If the studies continue to show these things, this may be a "kinder, gentler" protease inhibitor, with less diarrhea and much less lipodystrophy of the type connected with protease inhibitors. Perhaps this will also mean less impact on body shape, but this is far from certain.

There are other once-a-day cocktails coming out. One very interesting study put together a cocktail combining Boehringer Ingleheim's Viramune (nevirapine) with Dupont's Sustiva (efavirenz) and BMS's Videx (DDI), creating a once-a-day cocktail without any use of protease inhibitors. (Videx now comes in a simple small capsule that is much easier to take than the giant alka-seltzer size pill from the old days). The 26 people in this study did very, very well (90% had very low viral loads after one year). This is still preliminary, so it is not yet recommended until other studies can confirm this-but it is one to watch for.

A new kind of drug, Gilead's Tenofovir, will also be a once-a-day drug when it is approved by the FDA.

Energizer Protease

Dupont is developing two second generation protease inhibitors (DPC 681 and DPC 684) that could work on virus that is highly resistant to ALL of the other FDA approved protease inhibitors. They tried these new protease inhibitors against virus that was resistant to four or more protease inhibitors, and they look good against all of them.

Sticky Protease

A Washington scientist has discovered a protease inhibitor with a special property. No matter what HIV does this protease inhibitor usually sticks to the virus and stops it. The drug is being tested by Tibotec, a drug company in Belgium.

New NNRTI's

A real problem with NNRTI drugs, like Sustiva and Viramune, is that they are very cross resistant. This means if your virus gets resistant to one, it is probably resistant to both. Good news is that Tibotec is making a similar drug temporarily called TMC120 that works when the other two fail. Stay tuned for results of tests in people to see if this happens as predicted.

Nucleotides

Gilead's Tenofovir fights virus resistant to nukes (drugs like AZT, DDI, 3TC and ABC), even though it is a similar type of drug. We have hopes it will be the next drug available to the community. It is a once-a-day, quite powerful antiviral. People who really need this new chance at getting their virus down should get their doctors to call 1-800-GILEAD-5 and those in Europe can call 33-1-44-90-34-46. This puts you in contact with the company's compassionate use program. The eligibility for these programs is limited but it maybe an important option for some.

Entry Inhibitors

Entry inhibitors stop HIV from getting into cells. These new drugs will transform the world of HIV therapy because people who have used up their options will still respond to these types of drugs. The side effects of these drugs will be different and hopefully less serious than those of the drugs we use today. If the studies of T20 that are now starting are successful, Roche will be marketing the first of the inhibitors, T-20 soon. You might call your local study centers if this is of interest to you -- those eligible are anyone who has already had resistance develop to at least one medicine in each of the three drug classes that we use to make up present day cocktails, and who are ready to switch to a new combo.

Future Directions

Many new drugs are in the planning stage. Panacos Pharmaceuticals is working on a new powerful kind of inhibitor, 4 methyl DCK that works early in the life cycle of HIV.

Achillon Pharmaceuticals is developing a new nuke that avoids mitochondrial toxicities. This means it may be less toxic than drugs we take now. It also appears to be powerful against virus that is very nuke resistant. It is called ACH-126,443.

Triangle Pharmaceuticals is testing DAPD, a new nuke that works on virus resistant to both AZT and 3TC.

Another thing on the horizon is a booster for certain drugs. It appears that mycophenolic acid makes Tenofovir, ABC and DDI stronger.

Early experimentation is showing a cocktail of DDI, Ribavarin and Interferon Alpha fights BOTH HIV and hepatitis C!!! This would be a very important discovery for the many people who are co-infected with hepatitis C and HIV.

New Tools

Several companies, including ViroLogic, have new tests that help doctors decide if a drug is still effective at holding back the virus. These tests are called "phenotypic and genotypic resistance assays." Shortly, the Commonwealth of Massachusetts will be funding these tests through Medicaid. Medicare already does this, as do most private insurance companies. This is very good news for people whose regimens are failing and need to know which drugs are not working.

This article was reviewed by Dr. Cal Cohen, Research and Medical Director of Community Research Initiative of New England.

For more information contact Search For A Cure at hope@sfac.org