AIDS Treatment Update, Issue 59, November 1997
Edward King

**Twice-daily indinavir

One trial (known by the code 069-00) will test the licensed PI indinavir in a new twice-daily dose regimen. Studies suggest that instead of taking 800mg three times a day, as in current practice, it may still be possible to maintain adequate drug levels with a more convenient regimen of 1200mg twice a day.

Trial participants must have CD4 counts greater than 100, viral load greater than 10,000, and have never taken either 3TC or a protease inhibitor before. They will be assigned to take AZT plus 3TC, with the addition of indinavir either twice or three times daily. People who experience AZT side-effects can switch to d4T instead.

The effectiveness of the regimens will be compared by monitoring how well viral load is suppressed during 24 weeks of therapy.

**141W94 vs. indinavir

Another study (known as PROAB3006) will compare the anti-viral effects of the licensed PI indinavir with those of Glaxo Wellcome's experimental PI called 141W94.

Participants must have viral load greater than 400 and have been taking NRTIs for at least 12 weeks, but must not have taken a PI before. They will be randomly assigned to take indinavir at its standard dose of 800 mg three times daily, or 141W94 at a dose of 1200 mg twice daily. The drugs' effects will be compared by monitoring viral load changes over 96 weeks of therapy. The trial rules allow for changes in treatment if the fall in viral load during the first 8 weeks is less than 0.7 logs, or if it is above 400 after 16 weeks.

**DMP-266

DMP-266, now also known as efavirenz or by the brand-name Sustiva and made by DuPont-Pharma, is an NNRTI - the family of anti-HIV drugs that includes nevirapine, delavirdine and loviride. Pilot studies suggest that it is one of the more active antiretroviral drugs when given on its own, and it only need to be taken once daily; ongoing trials are testing it in combination with other drugs to delay the onset of resistance.

The latest trial (known by the code 006-020) will compare the benefits of taking either indinavir alone or both DMP-266 and indinavir, in addition to one or two new NRTIs. Participants must have taking NRTIs for at least 8 weeks, must never have taken any other NNRTI or PI, and must have a CD4 count greater than 50 and viral load greater than 10,000.

The effectiveness of the study arms will be assessed by comparing viral load changes during 24 weeks of treatment, and testing for the development of resistance. Participants will be allowed to switch therapy if they experience significant viral load increases after they have been in the trial for over 16 weeks.

**Abacavir

Two further trials are studying Glaxo Wellcome's new NRTI abacavir (previously known as 1592U89).

The CNAAB3002 trial will enrol people with CD4 counts above 100 and viral load between 400 and 50,000, who are currently taking any combination of anti-HIV drugs, but have not received more than 18 months prior therapy. They will be assigned to take either abacavir or an inactive placebo. The trial will look for differences in viral load suppression over 48 weeks of treatment.

Any participant whose viral load increases significantly during the first two months on the trial, or whose viral load is ever found to be above 5,000 thereafter, will be allowed to make any necessary changes to their underlying anti-HIV therapy and will be given abacavir on an open label basis.

A second abacavir trial, known as CNAB3005, will compare the antiviral effects of triple therapy using abacavir versus triple therapy using indinavir. Participants must have CD4 counts above 100, viral load above 10,000, and must not have taken anti-HIV drugs before.

Everyone will receive AZT and 3TC in the new combined tablet formulation, plus either abacavir or indinavir. The effects on their viral load will be monitored for 48 weeks. People whose viral load remains greater than 400 after 16 weeks of treatment will be allowed either to remain on their study treatment, or to switch to open-label therapy.

**Trial sites

City Hospital, Edinburgh Sheila Morris 0131-536 6342 Participating in abacavir trial 3002

Claude Nicol Centre, Brighton Nicola Perry 01273 664532 Participating in 141W94 and DMP-266 trials

Kings College Hospital Dee Graham 0171-346 3478 Participating in abacavir trial 3005

Kobler Centre Sandra Davies 0181-746 8000 bleep 0388 Participating in DMP-266 and abacavir trial 3002

Mortimer Market Centre Dr Ian Williams 0171-530 5000 Participating in abacavir trial 3002

North Manchester General Hospital Cynthia Murphy 0161-720 2845 Participating in abacavir trial 3002

Nottingham City Hospital Alison Cargill 0115-962 7746 Participating in 141W94

Royal Hallanshire Hospital, Sheffield Dr Bradbury 0114-276 6928 Participating in 141W94

Royal London Hospital Dr Celia Skinner 0171-377 7308 Participating in abacavir trial 3005

Royal Free Hospital Deborah Farmer 0171-794 0500 bleep 660 Participating in all trials

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