AIDS TREATMENT UPDATE, September 1995
Stephen Holmes

Two London clinics hope to start recruiting soon for a new trial testing combinations of anti-HIV drugs. The international trial, called AVANTI, has already been running for some time in other European countries. It is designed to be an evolving, ongoing study, adding new arms to test new combinations as time goes on.

All the places in the first phase have already allocated in other countries. 100 participants will receive a year's treatment with AZT plus 3TC or with the triple combination of AZT, 3TC and loviride. Participants must have CD4 counts between 150 and 300 and not have taken any anti-HIV drugs before.

New volunteers are now being sought for the second phase of the trial, known as AVANTI 2. They will receive either the dual combination of AZT plus 3TC, or the triple combination of AZT, 3TC and indinavir, Merck's protease inhibitor previously known as MK-639. The entry criteria remain the same as the first phase.

In the UK, AVANTI 2 will recruit participants from two London clinics - the Royal Free Hospital and the Kobler Centre. Each clinic will be able to enrol 6 participants. For contact details see the side-bar on this page.

Growth hormone

The Kobler Centre and St George's Hospital in London are currently recruiting participants for a trial examining the use of human growth hormone during treatment for acute opportunistic infections.

Human growth hormone has shown promising preliminary results as a treatment for people with AIDS-related wasting. Doctors at St George's Hospital in London argue that one of the most important times when weight loss occurs is during opportunistic infections. Their research suggests that only one-third of people who lose weight during an opportunistic infection regain that weight after the infection is treated.

The trial will test whether treatment with human growth hormone for two weeks after diagnosis with an opportunistic infection such as PCP or systemic CMV disease can help to prevent weight loss.

All participants will be offered nutritional support from a dietician and, if necessary, supplements to ensure that their nutrient intake is sufficiently high. Half will also receive human growth hormone, while the other half receive a placebo.

For more information on this study, contact the Kobler Centre or St George's Hospital. Contact details are given in the side-bar on this page.

Hydroxyurea & ddI

The preliminary results of a trial testing the combination of hydroxyurea and ddI were reported at a conference in Lisbon last month.

Based on test-tube experiments, researchers believe that the combination should have strong anti-HIV effects. For more information, see the article in AIDS Treatment Update issue 26.

The pilot study enrolled 12 asymptomatic people with CD4 counts above 250. After 3 months treatment, all experienced substantial drops in the level of HIV in their blood (viral load), and their average CD4 count rose from 392 to 573. The lack of a control arm of people taking no treatment, or just ddI, makes it hard to assess the significance of this result. Properly controlled trials are getting underway.

Major combination trial results due

The preliminary results of one of the largest trials of combination anti-HIV therapy are due to be released in September.

The American study ACTG 175 will report its findings in early September. ACTG 175 is comparing the effectiveness and side-effects of AZT monotherapy, ddI monotherapy, AZT plus ddI combination therapy and AZT plus ddC combination therapy. It will assess which regime is the best at preventing or delaying the onset of AIDS-defining illnesses, a 50% decrease in CD4 count and/or death. It enrolled over 2,000 people who had not been diagnosed with AIDS and had CD4 counts between 200 and 500.

The Data and Safety Monitoring Committee of the Delta trial will also meet in September, and it is possible that they will decide to release some preliminary findings. The Medical Research Council has been running Delta in conjunction with centres in France, Holland, Italy, Switzerland and Australia for over 4 years. The trial compares the effects of AZT monotherapy, AZT plus ddI combination therapy, and AZT plus ddC combination therapy. It has enrolled people with AIDS as well as those with no symptoms, and people who have taken AZT before as well as those without any prior treatment. Again, it is looking at the drugs' effects on clinical disease progression and survival.

Previous, smaller trials of combination therapy have suggested that combinations are better at boosting CD4 counts and reducing levels of HIV in the blood, compared with monotherapy. However, many researchers believe that these large trials offer the best chance of showing whether combinations are superior to single drugs at preventing illness or death, as opposed to their effects on laboratory test results.

Quattro started

The Medical Research Council's Quattro trial has begun recruiting. The first person started treatment on 2nd August. The trial is restricted to the following London centres: St Mary's Hospital, the Kobler Centre, the Victoria Sexual Health Centre, the Mortimer Market Centre, the Royal Free Hospital, St Bartholomew's Hospital, St George's Hospital, King's College Hospital and St Thomas' Hospital.

To be eligible you must have a CD4 count between 50 and 350 and be keen to start HIV drugs for the first time. Three treatment regimes are being compared: - concurrent combination treatment with AZT, 3TC, loviride and ddC for at least 64 weeks - cyclical treatment for 8 weeks with AZT, then 3TC, then loviride, the ddC (then all repeated) for at least 64 weeks - AZT plus 3TC combination treatment for at least 64 weeks

All treatments are with open-label drugs, so you will know which arm you have been assigned to.

Contact details for trials mentioned above:

Kobler Centre 369 Fulham Road, London SW10 9HT. Tel. 0181-746 8000 For AVANTI, contact Dr Graeme Moyle. For human growth hormone, contact Dr Dan Sharpstone.

Royal Free Hospital Pond Street, London NW3 2QG Tel. 0171-794 0500 Contact Deborah Farmer on bleep 660.

St George's Hospital Blackshaw Road, London SW17 0QT. Tel. 0181-672 1255 Contact Nick Patton.

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