Atazanavir boosts intracellular saquinavir levels: data on important new dual-boosted regimen

Graham McKerrow, HIV i-Base

Two British studies of the co-administration of atazanavir (ATZ), saquinavir (SQV) and ritonavir (RTV) found that ATZ increased plasma and intracellular (IC) exposure and Cmin of SQV but not RTV, and that the IC concentrations were higher than the plasma concentrations for all the PIs. The researchers conclude that the addition of ATV to a daily SQV/RTV regimen may be useful for people whose SQV concentrations are below the effective level.

Both studies of HIV-positive patients were carried out by Jennifer Ford and colleagues at Liverpool University, Chelsea and Westminster Hospital and Roche Products. In the first they looked at drug concentrations in nine patients on SQV/RTV 1600/100mg daily, and ten months later they recorded the drug concentrations in the same patients now on SQV/ATV/r 1600/200/100mg. [1]

They found that median plasma SQV exposure was significantly increased with ATV, although no change in median RTV plasma exposure was seen. Median IC SQV AUC was significantly increased but there was no change in IC RTV exposure.

In their second study, blood samples were taken from 12 patients receiving SQV/ATV/r 1600/200/100mg once daily. [2] They recorded higher IC concentrations than plasma concentrations for all the PIs and they write that mechanisms of IC PI accumulation may reflect affinities for influx transporters, since they did not observe any relationships with efflux transporters.

The higher intracellular concentration of saquinavir in this particular once-daily combination may provide and important opportunity for dual-PI boosted treatment, in patients with previous PI experience, or in patient lokking for a nucleoside-sparing regimen,


  1. Ford J, Boffito M, Wildfire A et al. Effect of atazanavir in intracellular and plasma pharmacokinetics of saquinavir and ritonavir administered once daily in HIV infected patients. 7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract PL6.3
  2. Ford J, Boffito M, Wildfire A et al. Intracellular and plasma pharmacokinetics of saquinavir, atazanavir and ritonavir (SQV/ATV/r) 1600/200/100mg administered once daily in HIV infected patients/TI. 7th ICDTHI,14-18 Nov, 2004, Glasgow. Abstract PL6.3

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