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T-20 Study
written by Jules Levin

This paragraph is reprinted from an article about T-20 posted to the NATAP web site in the HIV Drugs section (link-up). Please read that article if you would like more information. T-20 is the first fusion inhibitor showing HIV activity in humans. Its mechanism of action is different than that of current therapy approaches. It binds to the HIV-1 particle and prevents it from fusing and entering the CD4 cell. By fusion and entry, the components necessary for viral reproduction are injected into the CD4 cell. If you can prevent the process, the genetic material (RNA) for the virus cannot enter the CD4 cell and the virus cannot reproduce itself. By this mechanism, if successful, new infection can be prevented. Currently available antiretroviral therapy works differently. After viral entry into a CD4 cell reverse transcriptase inhibitors and protease inhibitors work to inhibit the reproduction process but the components for viral reproduction are in the cell.The first results of T-20 in humans were reported at the '97 IDSA meeting about one year ago. In the previously posted article is a color picture depicting the mechanism of action of T-20.

In that first human study, 16 HIV infected treatment nave and experienced individuals were randomized to receive one of four dosing regimens. At the highest dose tested, 100 mg every 12 hours, viral load was reduced by 1.50 log at day 14 of this 14 day study. 4/4 were undetectable using the bDNA test (limit of detection with bDNA: 500 copies/ml). Using the ultrasensitive test viral load was reduced by 2.0 log but at day 14 no one had <50 copies/ml..

The second study (protocol # TRI-003) of T-20 is about to begin at 12 sites across the US. The list of sites are listed below.TRI-002 was initially designed as a 6 month study to enroll indinavir failures, so it was a salvage therapy study. After 10 days of T-20 monotherapy participants were going to add nelfinavir+saquinavir+efavirenz. This study was replaced by TRI-003. In new TRI-003 design, T-20 will be administered for 28 days to 78 HIV-infected individuals either on no current antiretroviral therapy or on a stable regimen for at least 6 weeks prior to receiving T-20; and, your baseline viral load must be greater than 5,000 copies/ml. This means that you cannot change or add any new drugs during the study or up to 6 weeks prior to the study starting.

At present, there is no extension of the study where T-20 is administered on a longer-term basis. This means after 28 days participants will have to stop taking T-20. A rollover study (TRI-005) is planned for 003 participants making available T-20 on a continuing basis. Participants in 003 may stop dosing in October. The company will then conduct the analysis to identify two doses for 005 which is planned to begin in December. The start of 005 will be awaiting the finish of the toxicology study in animals. Currently, the company expects the animal data to be collected and analyzed in a timely fashion for the start of 005 in December. If both administration techniques are successful in 003, they will likely both be used in 005 (CSI and SQI).

Importantly, two methods of administration of T-20 will be explored in this study: continuous subcutaneous infusion (CSI) by a pump attached to the person (as an insulin pump is used for diabetes), or subcutaneous injection (SQI). Individuals randomized to the pump infusion will receive one loading dose of 100 mg one time at the beginning of he study. T-20 will be given by CSI at 4 dose levels: 12.5 mg, 25 mg, 50 mg and 100 mg. Two dose regimens will be used when T-20 is administered by SQI: 50 and 100 mg, both bid.

Entering any study during the early phases entails certain risks. In this case, the appropriate dosing regimen has not been identified. Since your viral load is >5,000 copies at entry you are likely to be adding T-20 to a failing regimen. If your viral load is 40,000 copies/ml, merely adding T-20 may not reduce your viral load to undetectable, which may allow the development of resistance to develop. Generally, the side effects and toxicities of a drug may not be identified until the drug has been studied more extensively. It's not unusual for some side effects not to emerge until several thousand patients have continuously taken a drug for a year or two.

Company officials report no CNS penetration by T-20 in animals because it's a big compound. However, the company says they are trying to develop smaller molecules to inhibit fusion. Additionally, company officials stated they have observed a 1:1 exposure rate of T-20 in plasma and lymph tissue in animals.

The study has started. If you are interested in getting more information about this study, the sites and study investigators where it will be conducted follow: