AIDS TREATMENT UPDATE, Issue 27 - March 1995
Edward King

To date, AG1343 has only been tested for its absorption and side-effects in ten uninfected people. The results of these studies were reported at the Washington conference at the end of January. They found that a high proportion of each dose of AG1343 is absorbed into the bloodstream, especially when it is taken at the same time as a meal or snack. The drug penetrates widely into body tissues, including the brain and lymph tissues. The only reported side-effect was mild nausea and flushing in one participant.

Test-tube experiments have shown that AG1343 inhibits a range of HIV strains, including AZT-resistant virus taken from people with HIV as well as laboratory strains.

Resistance

Because nobody with HIV has taken AG1343 before, there is no information on the risk of HIV developing resistance against the drug. However, resistance to protease inhibitors has emerged as a major concern to researchers.

The latest generation of protease inhibitors, which includes compounds made by the drug companies Abbott and Merck, have all had powerful anti-HIV effects in the test-tube and for the first few days or weeks when taken by people. However, like other anti-HIV drugs, the antiviral effect of the protease inhibitors soon fades coinciding with the development of strains of HIV with the genetic mutations associated with reduced sensitivity to the drugs.

The most worrying news is that HIV that has become resistant to one protease inhibitor may also be resistant to several others. This cross-resistance may mean that people who take one drug and develop resistance may then be unable to benefit from other, possibly more effective drugs that may become available later. Based on experience with other anti-HIV drugs, it is possible that the drug-resistant virus will gradually revert to drug-sensitive strains once the treatment is discontinued. Nevertheless, the issue of resistance is an important consideration for people considering taking part in clinical trials of protease inhibitors, and a reminder that trials may have unpredictable negative consequences for participants as well as offering possible benefits.

Trial details

The Kobler Centre trial of AG1343 is a phase II open-label study. To be eligible you must have a CD4 count between 200 and 500, and must not have taken anti-HIV drugs during the last year. Participants will take AG1343 in capsule form every 8 hours with a meal or snack, for four weeks. Because this is an early trial studying how well the drug is absorbed into the body, thorough physical examinations and blood tests will be required. Blood will be taken five times on the first day and on seven other occasions during the month-long trial.

Only 25 participants will be recruited. For more information, contact Dr Mike Youle on 0181-846 6161.

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