DuPont Merck reports that preliminary findings of a multiple dose healthy volunteer study indicate that concomitant administration of efavirenz 600 mg once daily and Fortovase 1200 mg tid results in a decline in plasma efavirenz concentrations of about 10%, an amount not believed to be clinically significant. However, plasma saquinavir concentrations declined by about 60%, which is anticipated to be clinically significant. DuPont Merck strongly recommends that doctors not use Fortovase with efavirenz if Fortovase is the only protease inhibitor used in the combination, unless there is no other option. All other saquinavir containing double-protease regimens are discouraged. Currently, there is no data available to guide appropriate dosing of ritonavir+saquinavir with efavirenz. The outcome on saquinavir levels of a triple drug interaction is difficult to predict. DuPont Merck says the use of these 3 drugs in combination is not recommended. If no other treatment option is possible you should strongly consider the information reported here to avoid over or underdosing saquinavir or any of the other drugs used in a combination. A study evaluating the interactions of coadministration of ritonavir+Fortovase+efavirenz is planned, and data may be available by the Geneva AIDS Conference at the end of June.