What's on the New Drug Horizon?
Today, advances in anti-HIV and anti-HCV research are few and far between. Only a handful of new drugs are in development that block HIV reproduction in new ways. Most in development are simply improved versions or new variations of those now available. Such drugs may only offer small improvements in potency, simpler dosing and reduced side effects. Some will claim to be effective against drug-resistant viruses based on lab tests, but it remains to be seen whether they will truly offer help for people with highly resistant virus. This article briefly reviews these new drugs.
Results from a lab study shows that tipranavir is active against almost all the protease inhibitor-resistant viruses tested. In lab studies, it has been difficult to develop resistance to this drug. (This has been true for many other drugs only to later find that it can develop quite readily.)
Early formulations used up to 30 pills a day. A new capsule formulation has been created that allows for better absorption into the body. This new formulation should allow for twice-a-day dosing as well as fewer pills per day.
Tipranavir is also being studied together with ritonavir (Norvir), which greatly boosts its levels. It is hoped that this combination will be useful for people with protease inhibitor resistance. Its development was delayed due to the formulation problem and the fact that it was sold by its original owner, from Pharmacia & Upjohn to Boehringher Ingelheim. Wider access to the drug will probably occur in 2002.
BMS-232632: Bristol-Myers Squibb's first protease inhibitor is designed for once daily dosing. Lab studies suggest that it may remain sensitive to viruses resistant to other protease inhibitors, but it remains to be seen whether this will be the case in people.
One study shows that the drug is reasonably potent. About 60% of the participants achieved viral loads below 400 copies HIV RNA and 40% were below 50 copies after 16 weeks. The most common side effects seen so far are mild-to-moderate diarrhea and elevated bilirubin levels (a measure of liver function), which normalized after stopping or reducing the drug to the lowest dose studied.
The NNRTI furthest along in development is Triangle Pharmaceuticals' emivirine. Studies show that it has the same resistance patterns as other NNRTIs, and most researchers believe it will not benefit people already resistant to other NNRTIs. Emivirine is dosed twice a day and is quite well tolerated. The most common side effects are gastrointestinal distress and rash, although at a much lower incidence than nevirapine (Viramune).
Triangle Pharmaceuticals' FTC is very similar to 3TC (lamivudine, Epivir) and it has the same resistance profile. However, FTC appears to be more potent and is only dosed once a day. Like 3TC, FTC is also active against hepatitis B.
Tenofovir: Studies show that Gilead Sciences' tenofovir is significantly more potent against HIV than their other drug, adefovir. Tenofovir is also dosed once a day and lab studies suggest that it remains active against most NRTI-resistant viruses. Furthermore, studies show that there are few or no kidney side effects, a common problem with adefovir. Tenofovir is likely to be approved before the end of 2001. The drug is available free of charge under a limited expanded access program for people unable to make an effective combination without it. Call Project Inform's Hotline for more info.
One drug getting a lot of attention in the past year is pentafuside (T-20), being developed by Trimeris and Hoffman-La Roche. It belongs to a class of drugs called fusion inhibitors, which work by physically blocking HIV from attaching to CD4+ cells.
Studies show that T-20 is effective as third line therapy, even in people who are resistant to all current protease inhibitors. Getting a long-lasting response, however, requires it to be paired with at least one other anti-HIV drug that the person still responds to. Pentafuside has to be given through injection under the skin (subcutaneously) twice a day.
The only significant side effects reported so far are problems at the injection site, ranging from minor discomfort to long-lasting bruises and sores. This can limit a person using the drug since there are only a few places where the injections can be given.
For information on how to participate in drug trials, call 1-800-TRIALS-A or go online to http://hivinsite.ucsf.edu.
The FDA recently approved Schering-Plough's pegylated interferon-alfa (Peg-Intron). This new formulation binds alfa-interferon to a chemical called polyethylene glycol, which makes it stay longer in the bloodstream than standard interferon-alfa.
The FDA approved using peg-interferon alone and not combined with ribavirin (Rebetol). One large study showed that Peg-Intron was about twice as effective in controlling HCV replication than standard interferon-alfa. However, more people developed mild bone marrow suppression.
The results of peg-interferon alone are comparable to those seen with standard HCV therapy (standard interferon-alfa and ribavirin, bundled as Rebetron). However, more recent results suggest that combining peg-interferon with ribavirin will be more effective. Dosed subcutaneously, peg-interferon is dosed only once a week while standard interferon-alfa is dosed three times. Another pegylated interferon-alfa (Pegasys) being developed by Hoffman-La Roche is expected to be approved before the end of 2001. This, too, will be dosed once a week.
This article was provided by Project Inform. It is a part of the publication WISE Words. Visit Project Inform's website to find out more about their activities, publications and services.