WASHINGTON — The best strategy for using two of the newest anti-HIV drugs, tipranavir and enfuvirtide, may be to use them together because each appears to work better when coupled with at least one other active antiretroviral drug, several experts recommended at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
After enfuvirtide, an HIV-fusion inhibitor that's administered as a subcutaneous injection, was approved by the Food and Drug Administration in early 2003, “a lot of physicians shied away from using it, perhaps because it's an injectable or perhaps because they didn't have other drugs to partner with it,” said Michael S. Saag, M.D., professor of medicine at the University of Alabama, Birmingham.
“Finding the right time to pull the trigger and use enfuvirtide is a challenge, but waiting too long can cut patient responsiveness to the drug,” Dr. Saag added. “With tipranavir becoming available, there will be a lot more use of enfuvirtide.”
A new analysis of the data collected during the phase III trials that led to enfuvirtide's licensing highlighted the importance of starting enfuvirtide treatment sooner rather than later, said Calvin J. Cohen, M.D., an internist in group practice in Boston.
This posthoc analysis identified four factors that were each associated with enfuvirtide treatment leading to a marked drop in a patient's viral load:
1. Starting enfuvirtide treatment when the patient had a CD4 count of more than 100 cells/μL.
2. Starting treatment when a patient's viral load was less than 100,000 RNA copies/mL.
3. Having at least two active antiretroviral drugs in the regimen.
4. Treating patients who had previously been treated with no more than 10 antiretroviral drugs.
“Delaying initiation of enfuvirtide may be associated with a reduced likelihood of response,” Dr. Cohen said at the meeting, sponsored by the American Society for Microbiology. “In some cases, it may be in the patients' best interest to use enfuvirtide when tipranavir is available.”
Both Dr. Saag and Dr. Cohen have been investigators in studies using enfuvirtide that were sponsored by Trimeris Inc. and Roche Laboratories Inc., the companies that market enfuvirtide, and both have also served as speakers for these companies.
Study results presented at the meeting on the new protease inhibitor tipranavir also suggested that this drug would work best when coupled with at least one other active antiretroviral drug. Because tipranavir will likely be used on patients infected with HIV that's become resistant to standard protease inhibitors, these viruses are also often resistant to the other drugs that are frontline agents for treating HIV. When tipranavir is begun, enfuvirtide may be one of the few agents left that's still effective against a patient's infection.
“Long-term success with tipranavir is likely to require coadministration with other drugs that are active against a patient's specific HIV variant, which may include drugs from new classes such as enfuvirtide,” Joseph J. Eron Jr., M.D. said at the meeting. Dr. Eron, director of the AIDS clinical trial unit at the University of North Carolina at Chapel Hill, has worked in studies of tipranavir sponsored by Boehringer Ingelheim Pharmaceuticals Inc., which makes tipranavir, and he has served as a speaker for Roche and Trimeris.