Press room ... 1996 archive

Notes on Combining Protease Inhibitors

April 21, 1996

San Francisco, CA—There has been a lot of discussion on combining protease inhibitors, especially ritonavir and saquinavir. Animal studies suggest that when combining these two drugs, saquinavir levels increased by an astounding 29,000%. Ritonavir also increased drug levels of other protease inhibitors when they were combined: indinavir levels increased 800%, nelfinavir levels increased 1,000% and VX-478 (BW141) increased 800%. It is still not known whether similar increases will be found in humans. Additionally, there is likely to be changes in drug levels when when indinavir or nelfinavir (or any other protease inhibitors) is used in combination with other protease inhibitors. People should therefore be discouraged from combining protease inhibitors as this could cause severe side effects.

Abbott Laboratories and Roche are starting a study to better understand what happens in humans when ritonavir and saquinavir are used in combination. This study will enroll 120 people with 100-500 CD4 cells and who have a viral load of more than 5,000 copies of HIV RNA. This will be a randomized open label study which will be conducted at 7 sites (including San Francisco) and will last for 48 weeks. The doses used will be:

400mg ritonavir twice a day + 400mg saquinavir twice a day or
600mg ritonavir twice a day + 400mg saquinavir twice a day
If no dose limiting side effects are seen with these doses then higher doses will be used:

400mg ritonavir twice a day + 800mg saquinavir twice a day or
600mg ritonavir twice a day + 600mg saquinavir twice a day
The current study design does not allow people to take nucleoside analogues with the protease combination, however, if you do not have a drop in viral load or if your viral load rebounds then you can add two nucleoside analogues. If you are intolerant to the protease combination then the dose(s) will be reduced, if still intolerant then one of the protease inhibitors will be discontinued and 2 nucleosides can be added.