AIDS Treatment Update, Issue 40, April 1996
Keith Alcorn

Merck is legally prevented from publicising the availability of the drug on a named patient basis, but AIDS Treatment Update has learnt that supplies will become available during May. However, it is unclear how much drug will be available in the UK.

Doctors will be told that they can obtain the drug foranyone they believe might benefit from it, but it will be left up to doctors to decide who should get the drug.

The licensing authorities in the USA have suggested that all people with HIV might benefit from taking a protease inhibitor. Last month the FDA approved both indinavir and ritonavir for use by any HIV-positive person 'where anti-retroviral therapy is warranted', an exceptionally wide licence intended to let doctors make up their own minds how to use the drugs.

British doctors such as Dr Ian Williams of the Mortimer Market Centre in London have expressed caution about prescribing the drug when so little is known about its long-term effects. "I still wouldn't use it for first- line therapy. So few people have taken this drug I would not be happy to prescribe it widely. We don't know enough about long-term toxicity, we don't know how long the response lasts for, and we don't know enough about resistance. At the moment I would give it only to people who are not tolerating first-line treatment or who aren't doing well on first- line treatment."

However, the number of people who fall into these two categories is likely to be large. Based on an AIDS Treatment Update survey of UK clinics last November, there are up to 1000 people with CD4 counts below 50 who might be considered for protease inhibitor treatment in the first half of 1996 alone if the drugs were available on a compassionate basis. This figure is likely to underestimate the demand, since clinicians were asked only about the likely demand for saquinavir, a drug currently considered inferior to other protease inhibitors.

Dr Ian Williams says that the other consideration which will influence prescribing of the drug is cost - Merck say it plans to charge clinics about £33,000 a year.

"That's nearly twice the cost of AZT. While I would like to be able to prescribe it, we will have to think very carefully about who we give it to". The prices set by manufacturers in the USA suggest that other protease inhibitors will cost even more. Saquinavir is likely to cost around £33,800 per year, and Abbott's ritonavir will cost over £34,300 per year.

* The promise...and the doubts

AIDS Treatment Update first reported on the promise of protease inhibitors in January 1995 - just fifteen months ago. At the time the big story was the success of AZT and 3TC, providing the first hint that combination therapy might be substantially better than treatment with one drug alone. Since then it has become clear that protease inhibitors have an extremely important role to play in HIV treatment. Recent issues of AIDS Treatment Update have reported that:

- Triple combinations that include a protease inhibitor can reduce viral load to extremely low levels, and this drop may be sustained for longer than has been seen with previous drug regimens

- The protease inhibitor ritonavir prolongs life, reduces the risk of opportunistic infections and boosts the immune system in people with advanced HIV disease

- In some cases protease inhibitors can boost CD4 counts from 50 to above 200

Understandably, this evidence makes many people very keen to take the protease inhibitors.

However, with the exception of one ritonavir trial which enrolled over 1000 people, these results come from fairly small studies without clinical endpoints. Only 100 individuals have taken indinavir for more than 48 weeks in combination with nucleoside analogues. Virtually no-one has been followed for longer than six months on ritonavir. To date, triple combinations have been studied only in very small groups of people. A French study of ritonavir, AZT and ddC reported in AIDS Treatment Update last month reported on just 32 participants, eleven of whom dropped out of the study because of side-effects.

* Who should get access first?

Since doubts remain over the bestay to use protease inhibitors, who should receive them first? Doctors we spoke to agreed that people with the lowest CD4 counts, very high viral load or no further licensed treatment options should be given the highest priority. It is this group of people for whom doctors are most likely to seek named patient supplies of protease inhibitors.

In theory, however, healthier people who may not have irreversible changes in their immune systems might derive greater benefits from the drugs than people with advanced disease. But it is likely to take at least two years, if not longer, to define how protease inhibitors are best used in individuals with higher CD4 counts and less advanced disease.

* When will they be licensed?

The only protease inhibitor which might conceivably be licensed in the UK within the next six months is ritonavir. AIDS Treatment Update has been told by the European Medicines Evaluation Agency that it is realistic to assume that ritonavir will approved for use by people with 'advanced HIV disease' by late summer.

The way ahead for other protease inhibitors is less clear. Companies will need to gather clear-cut data about clinical benefits if they want their drugs approved in Europe for anyone except people with very low CD4 counts. In other words, if you still have a relatively high CD4 count and you've never taken anti-HIV drugs before, don't bank on getting a protease inhibitor within the next year or so unless you join a trial. In the meantime it must be assumed that existing schemes to allow access to the drugs for people with advanced HIV infection will continue.

* The importation option

If you don't qualify for any of schemes described opposite and don't want to wait for the drugs to be licensed in the UK, you have the option of importing the drugs from other countries. British law allows you to import drugs that are already licensed abroad, provided that they are for your personal use and you have a private prescription from a doctor in the UK.

You can import drugs from international pharmacies, which allow EU citizens to import licensed drugs via Germany. The German AIDS organisation Deutsche AIDS-Hilfe recommends the Komtur Apotheke pharmacy in Freiburg (Zahringer Strasse 23, D-79108 Freiburg, Germany. Tel 00 49 761 504 230; Fax 00 49 761 504 2315). However, the NHS will not cover the cost of imported drugs; you will have to pay for them yourself. The cost is likely to be £33,000 to £35,000 for a year's supply.

Dr Mike Youle warns that you are unlikely to get the drugs any more quickly by this route than you would by applying to join one of the expanded access programmes. This is due to the production problems faced by Merck and Abbott; even doctors in the US are reportedly finding it hard to obtain the newly licensed protease inhibitors for long-standing patients.

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