AIDS TREATMENT UPDATE, Issue 28 - April 1995
Edward King

The PENTA 1 trial comparing early with deferred treatment with AZT has now enrolled 172 children (all infected by mother to baby transmission). The independent Data and Safety Monitoring Committee (DSMC) met in March and recommended that the trial continue as there has been no untoward toxicity and, although recruitment has been much slower than planned, the follow-up has been extremely good.

Following the full results of an American trial (ACTG 128) which showed no difference between high and low dose AZT in terms of efficacy and toxicity in children, the PENTA 1 protocol has been amended to allow pædiatricians to give a lower dose of AZT.

It was decided that no changes should at present be made to the PENTA 1 protocol following the early termination of the AZT monotherapy arm of another US trial, ACTG 152 (see AIDS Treatment Update issue 27). This used a higher dose of AZT than PENTA 1, and the other two arms of that study are continuing until August 1995. No detailed information has been released about toxicity or disease progression in the study. The PENTA 1 DSMC will meet again later this year and review more detailed information from ACTG 152 as it becomes available, as well as data from the large studies in adults comparing combination therapy versus AZT monotherapy or ddI monotherapy.

The PENTA 3 trial (a phase II trial of AZT plus ddC compared with AZT alone in symptomatic children not previously given antiretroviral therapy) has now started in Europe. For more information see AIDS Treatment Update issue 21/22.

A new trial to assess the safety and tolerability of adding 3TC to the child's current antiretroviral therapy is being planned and should start in the late summer.

* Delta and 3TC

The Medical Research Council has provided AIDS Treatment Update with the following news on changes in the Delta trial, the international study evaluating combination therapy with AZT plus ddI or ddC:

"The international co-ordinating committee of Delta has always believed it was important to respond flexibly to changes in current treatment practice. The debate about the use of 3TC as part of combination therapy (see AIDS Treatment Update issues 26 and 27) reinforces the need to perform large long-term studies with clinical end-points such as Delta. As yet no clinical data has emerged about AZT plus 3TC combinations and the surrogate marker data is difficult to interpret. Nevertheless the co-ordinating committee have been keen to make this combination available within Delta for those with progressive disease. A protocol amendment has therefore been prepared and your doctor has the details. We would urge you to stay in the study as long as possible as it is one of the few studies in the world able to answer the question of whether combination therapy does delay disease progression."

* 3TC and neuropathy

Doctors in the USA have reported a case in which 3TC appeared to worsen peripheral neuropathy in a person who already suffered from the condition. The man had previously developed neuropathy whilst taking ddC - a recognised side-effect of the drug. Eighteen months later when he started taking 3TC (which is chemically related to ddC), the neuropathy returned, and when he stopped taking 3TC the symptoms improved.

* Glaxo rations 3TC

Glaxo has announced a 'pacing programme' for new enrollees in the open label scheme for their experimental anti-HIV drug, 3TC. Worldwide demand for the drug has increased from about 550 new enrollments per month to over 4000 per month in just 4 months, following the release of promising results from trials testing the combination of AZT plus 3TC.

Glaxo says that by limiting new enrollees to 460 per week worldwide, the company will be able to continue to supply 3TC to people already enrolled, ensure that new people can be enrolled and provide adequate drug for trials, including the three large studies that will begin in the next few months. After each week's allocations have been used up, people will be placed on a 'first-come first-served' waiting list.

Robin Gorna of the European AIDS Treatment Group reacted angrily to the announcement. "Glaxo admits that its plans may 'inconvenience' people with HIV, but this is a mild term for preventing people with a life-threatening condition from acquiring the most hopeful drug to date."

Doctors can obtain 3TC through the expanded access scheme for HIV-positive people with a CD4 count below 300 who can no longer benefit from AZT, ddI or ddC because of side-effects or disease progression.

* Calcipotriol KS trial

Calcipotriol ointment is an approved, widely used treatment for psoriasis. It is a derivative of vitamin D that works by stimulating cell growth. There have been anecdotal reports that calcipotriol may be a useful treatment for Kaposi's sarcoma (KS) lesions on the skin. This trial aims to produce clear evidence by comparing the effects of the standard dose for up to 2 years, but may be more common at the higher doses.

The study is taking place at the Kobler Centre in London.

Kobler Centre Chelsea & Westminster Hospital 369 Fulham Road London SW10 9NH Tel. 0181-746 8000

Contact Sandra Davies, bleep 0388

9504
ATU2804

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