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Fusion inhibitors work by stopping HIV from getting inside T-cells by preventing them from joining, or fusing, with an HIV protein called gp41. When HIV does fuse with gp41, it forms a coillike structure, then allows HIV to enter an uninfected cell.
This month's column will focus on two fusion inhibitors that are potentially important treatments for people researchers refer to as "heavily pretreated." It also includes a very important note about the salvage therapy combination of Agenerase (amprenavir) and Sustiva (efavirenz) along with other drugs.
First of the New Class
Very promising results about one fusion inhibitor, T-20, were released at the ICAAC meeting. T-20 was tested in people who had already taken just about every other HIV drug available. Researchers reported that no one in the study had to stop because of side effects or drug intolerance. They reported that sixty percent of the study participants, the majority of whom started with a viral load over 75,000 and CD4 cells below 100, significantly lowered their viral load after sixteen weeks taking the drug.
Taking T-20 by itself would most likely eventually lead to resistance to the drug, so it is being studied as part of a treatment combination. The fact that people in this study reduced their viral levels, even after having taken many other HIV drugs, suggests that T-20 may work in cases where people have already developed resistance to other types of drugs, such as protease inhibitors.
Participants in this study were tested before they were given T-20 for resistance to existing HIV treatments. Resistance testing is done to see if the HIV has changed, or mutated, in a way that makes it unlikely that a specific treatment or treatment combination will work. In this study, most of the participants had virus mutations that were resistant to several other drugs, so the T-20 injections were given along with whatever other HIV drugs had the best chance of working.
One drawback of T-20, and of the other fusion inhibitor currently being tested, T-1249, is that they are not available in pill form. Participants in studies of these drugs, however, were able to manage the daily shots. Both T-20 and T-1249 have been given fast-track designation by the Food and Drug Administration. A study of T-20 in people who have already taken one or two protease inhibitor combinations has recently opened.
Participants in this new T-20 study will be divided into four groups. Three of the four groups will receive different doses of T-20 in combination with four other approved anti-HIV drugs: Agenerase (amprenavir), Sustiva (efavirenz), Ziagen (abacavir), and a small dose of Norvir (ritonavir). The fourth group will not receive T-20, but will still take the other drugs. T-20 is given by a twice-daily shot under the skin. There are no placebo (dummy) shots used in this trial.
The study will last for 48 weeks if people are doing well and no serious side effects occur. Clinicians and people with HIV can call Karen Cavanagh, R.N., at NYU Medical Center at (212) 263-8707 for more information. NYU also has several other new studies currently looking for participants. Call (212) 263-6565 to find out about these.
A Fast-Tracked Team
The company that invented T-20, Trimeris, is a small biopharmaceutical company. Much to its credit, Trimeris has focused on testing its fusion inhibitor in people who have already taken a lot of other HIV drugs. To help develop and test this new class of HIV drugs, Trimeris recently entered into an agreement with Hoffman-LaRoche, a very large drug company that sells several different HIV treatments.
This new team has recently begun testing another fusion inhibitor called T-1249. This drug is also supposed to work by attacking and blocking HIV from getting into uninfected cells. It is hoped that T-1249 will work against HIV that has become resistant to T-20 and against different strains of HIV from around the world.
Participants in the T-1249 study must be HIV-positive and have a viral load above 5,000. Five different doses of the drug will be given to study participants. At this stage of the study, participants are given either one 12.5 mg shot or two 6.25 mg shots a day. Study participation will last six to seven weeks. Study participants will have many tests done to see what effect the drug has on the immune system and HIV. Additional safety labs, such as monitoring of blood clotting mechanisms, are also performed in this study. Participants cannot be taking any anti-HIV medications, nor can they take any for the duration of the study. Several people who recently stopped taking their HIV medications, now referred to as a structured treatment interruption, have enrolled in this study. Contact Karen Cavanagh, R.N., at (212) 263-8707 for more information about this study.
Agenerase is a potential treatment option for people with extensive treatment experience. It is believed to be active against HIV that is resistant to currently approved protease inhibitors, although in studies the drug works best in people who are treatment naive. Nevertheless, some people take Agenerase in combination with an NNRTI type of drug such as Viracept (nevirapine) or Sustiva (efavirenz), along with other drugs such as abacavir, as salvage therapy.
Everyone in the T-20 study described above took four anti-HIV drugs -- Agenerase (amprenavir), Sustiva (efavirenz), Ziagen (abacavir), and a small dose of Norvir (ritonavir). The Norvir was recently added to the study based on reports that taking Sustiva along with Agenerase greatly reduces Agenerase levels in the blood. This could lead to the development of resistance to Agenerase. The makers of the drug recently sent a letter to doctors stating that adding 200 mg (two tablets) of Norvir to the combination of Agenerase, Sustiva, and Ziagen increased Agenerease levels back to an effective level. Adding the standard dose of Viracept (nelfinavir) also addressed the problem.
Anyone interested in learning more about fusion inhibitor studies or coverage of already approved HIV treatments and care can call the AIDS Treatment Data Network at (800) 734-7104. Another source of information is the national AIDS Clinical Trials Information Service (ACTIS) at (800) TrialsA. Be forewarned that some clinical trials now require some form of insurance coverage to pay for some of the drugs used in the study.
Ken Fornataro is Executive Director of the AIDS Treatment Data Network. For more information, call (800) 734-7104. Affiliation is provided for purposes of identification, not representation.
This article was provided by Body Positive. It is a part of the publication Body Positive.