AIDS TREATMENT UPDATE, Issue 38, February 1996
Edward King

Tucaresol was originally developed by Wellcome for treating sickle cell anaemia, an abnormality of the red blood cells. Initial studies in people with sickle cell anaemia and in healthy volunteers suggested that the drug stimulated the immune system, so a phase II study was started in people with HIV.

That study was stopped early when the first two participants developed side-effects of high fever, tender lymph nodes, rash, muscle aches and tiredness. These are thought to be related to the high dose that was used - 1000 mg every other day. The study is now resuming, testing tucaresol at much lower doses.

EFFECTS OF TUCARESOL

Test-tube studies have found that tucaresol stimulates the production of the cytokines interleukin-2 and gamma interferon. Cytokines are natural substances used by cells to communicate with other cells. Interleukin-2 encourages the growth of CD4 cells in the test-tube. Gamma interferon helps the body to fight infections. Both of these substances are often found at abnormally low levels in people with HIV.

In laboratory experiments, tucaresol also boosts cytotoxic CD8 cells, infection-fighting immune cells. Some studies have linked high levels of CD8 cells to a reduced risk of disease progression in people with HIV.

An artificially manufactured form of interleukin-2 has been studied as a treatment for people with HIV infection for over four years. Last year, American researchers reported startling increases in the CD4 count of HIV-positive people who received infusions of interleukin-2 every two months For more details, see AIDS Treatment Update issue 28.

Controversy lingers over the significance of the boost in CD4 count brought about by interleukin-2. Some researchers are concerned that the newly produced CD4 cells may not be fully functioning in their ability to help fight infections. Just because a person's CD4 count rises from, say, 250 to 450 after interleukin-2 may not mean that he has the same protection against infections as someone with a 'natural' (i.e. not drug induced) CD4 count of 450.

Because interleukin-2 stimulates the immune system, it also stimulates HIV-infected immune cells, causing an increase in HIV replication. For that reason it is important to take anti-HIV drugs at the same time. In the American study, interleukin-2 only boosted the CD4 count of people whose CD4 counts were above 200 before treatment. In people with lower CD4 counts, the treatment appeared to do more harm than good, increasing the amount of HIV in their blood, but not their CD4 count.

Little is known about tucaresol's likely effects among people with HIV. However, tucaresol has been given to two macaque monkeys infected with SIV, and caused reductions in levels of SIV in their blood.

TRIAL DESIGN

The trial is a dose-ranging study - everyone will receive tucaresol at one dose or another. The doses tested range from 25 mg once a week up to 50 mg three times a week. Participants will receive four weeks of treatment, and will then be followed up for a further twelve weeks. Regular visits to the clinic for blood tests will be necessary.

To be eligible, you must have a CD4 count of between 300-500, not have been diagnosed with AIDS and have been taking licensed anti-HIV treatments for between 3 and 12 months. You must never have taken immune-modulating treatments or experimental anti-HIV drugs before. For more details, call Celia Richardson or Dr John Walsh on 0181-746 8000.

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