Abbott Protease Inhibitor In Combination: Sustained Viral Load Drop

A clinical trial in France with about 25 volunteers combined ritonavir (the Abbott protease inhibitor) with AZT plus ddC, in patients who previously were untreated. The combination achieved a 2.5 log (more than 300-fold) average drop in HIV viral load, as measured both by HIV RNA and by infectious virus; this drop has been sustained for 20 weeks so far and is still continuing. This result was submitted by Jacques Leibowitch, M.D., a clinical immunologist at the Raymond-Poincare Hospital/University Rene-Descartes, Paris Ouest; it was apparently too late even for the late-breaker session, but a couple of Dr. Leibowitch's slides were shown in a late breaker presentation from Abbott Laboratories. And Dr. Leibowitch showed us some of his other slides when we met in the aisle during the conference.

The proportion of patients with at least a 99.9% drop in viral load has kept increasing over the five months of this trial, and has now reached over 50%.

We need to learn more details of this study. The continuing increase in the proportion of patients who respond very well to this treatment suggests that immune-system recovery may be helping the drugs to control the virus. If so, effective viral suppression might be sustained for a long time.

At the ICAAC conference, there was much discussion and interest in combining a protease inhibitor (either ritonavir or one of the others) with combinations of other antiretrovirals, especially AZT plus 3TC, or AZT plus ddC. There is nothing magic about these particular combinations, however; the goal is to get good viral suppression in addition to the suppression due to the protease inhibitors. For persons who have already used AZT for a long time, effective combinations of other drugs which they have not used might work better. This strategy needs more attention and research.

[Note: A larger trial, ACTG 229, combined a different protease inhibitor (saquinavir, developed by Hoffmann-La Roche) with AZT plus ddC. Viral suppression with the triple combination was better than in the other arms of that trial, but not nearly as good as in the new French study. The difference in results may be because patients in ACTG 229 had extensive prior use of AZT; all the volunteers had used it for at least four months, and most for more than a year. Also, ACTG 229 used a dose of saquinavir which many now suspect is less than the optimum dose.

[An Italian study found a 1.7 log (50-fold) viral load drop with the current dose and formulation of saquinavir, combined with AZT only. Hoffmann-La Roche is now conducting a major international study, which has already enrolled 2000 patients and will enroll 1000 more, which includes a treatment arm combining saquinavir, AZT, and ddC in AZT-naive patients.]

[Safety note: Ritonavir MUST NOT be combined with any of a number of other drugs, both common prescription medications and certain experimental treatments. Anyone using ritonavir -- which is not widely available -- must follow all instructions carefully.]