AIDS TREATMENT UPDATE, August 1995
Keith Alcorn

More than 5,000 people in Europe are receiving this drug through an expanded access scheme, and manufacturers Glaxo-Wellcome say that they will no longer ration the drug if the current rate of demand stays the same. 3TC should be available within four to five weeks to individuals who are unable to tolerate other anti-retrovirals or who have suffered disease progression despite treatment with AZT, ddC and ddI. Studies show that when used in combination with AZT, the drug has a better effect on viral load and CD4 counts than any other anti-viral combination yet tested, but evidence on the clinical benefits in terms of delays in disease progression is still awaited.

If you can tolerate AZT, another option is to join the existing trial of AZT, 3TC and loviride, where you stand a 75% chance of getting the AZT/3TC combination, and a 25% chance of getting the AZT/3TC/ loviride combination, theoretically the most potent combination in the study. However, this study excludes individuals with active opportunistic infections at the time of enrolment.

_ABT-538_

ABT-538, the protease inhibitor made by Abbott, has recently been given the name ritonavir. On its own, it seems to have a very strong anti-viral effect in the short term. Nothing is known about its effect when used in combination with other drugs, but it would be logical to assume that its anti-viral effect would be enhanced. A UK trial allowing people with CD4 counts below 100 to add the drug to their existing anti-viral treatment was planned, but this has been cancelled. Abbott says that they don't have enough drug for an expanded access scheme.

_Loviride_

This non-nucleoside reverse transcriptase inhibitor appears to have good anti-viral effects, and the theory is that if used in combination with AZT and 3TC it might produce long-lasting increases in T-cell counts. Loviride is not available through expanded access except to individuals who have already participated in a trial of the drug. A new trial testing higher doses of the drug has just begun at the Chelsea and Westminster Hospital, but this excludes people with CD4 counts below 100.

_MK-639_

MK-639, the protease inhibitor made by Merck, has been renamed crixivan. It appears to have a strong anti-viral effect in short term trials. No trials are available in the UK, although several London centres hope to participate in international studies. An expanded access programme is planned for people with CD4 counts below 50, but Merck will have enough drug to supply just 650 people outside the USA. Some of this drug will be available for people in the UK, although not before the late autumn.

_Saquinavir_

There have been several trials of this protease inhibitor, and it is likely to be the first protease inhibitor to be formally licensed. One trial suggests that used in combination with AZT and ddC it has a more potent anti-viral effect than the AZT/ddC combination alone. Expanded access programme for the US and Canada have already been announced. Manufacturers Roche are talking about making the drug available in Europe 'later this year', although it may be December before expanded access starts in the UK.

_Stavudine_

This nucleoside analogue, also known as d4T, is licensed in the USA. In Britain doctors can obtain it directly from the manufacturer, Bristol-Myers Squibb, for people who have failed on other nucleosides (AZT, ddI and ddC). Stavudine's most common side-effect is peripheral neuropathy (nerve damage), so it is not recommended for people who already suffer from peripheral neuropathy.

OF ALL THESE DRUGS, ONLY STAVUDINE HAS YET BEEN SHOWN TO HAVE ANY EFFECT ON CLINICAL SYMPTOMS OR SURVIVAL. THE EVIDENCE FOR THE EFFECTS OF THE OTHERS IS ENTIRELY BASED ON CHANGES IN RECIPIENTS' CD4 COUNTS AND VIRAL LOAD.

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