Raltegravir and unboosted atazanavir

With the interest in NRTI-sparing regimens containing two drugs it is important that we understand the optimal dosing strategies.  One aspect of this is the potential interaction between the components of the regimen.  Two studies have been published recently on the interaction between atazanavir and raltegravir, one a cross-over study in healthy subjects and the other a parallel study in HIV+ subjects.

Zhu and colleagues performed a cross-over study which assessed the two-way pharmacokinetic interaction of atazanavir (300 mg twice daily) with raltegravir (400 mg twice daily) in 19 HIV-negative volunteers.  [1]

Coadministration of atazanavir and raltegravir (300/400 mg twice daily) decreased atazanavir AUC0-12 by 17% and Cmin by 29%, relative to atazanavir alone. Raltegravir AUC0-12 increased by 54% and Cmin increased by 48%, relative to raltegravir alone.  Of interest, the incidence of hyperbilirubinaemia was similar after atazanavir (300 mg twice daily) alone or in the presence of raltegravir.

Cattaneo et al determined the pharmacokinetics of atazanavir (300 mg twice daily) and raltegravir (400 mg twice daily) in 22 HIV-positive people and compared them to values obtained from 24 HIV-positive people receiving raltegravir (400 mg twice daily) plus NRTIs.  [2]

Raltegravir trough concentrations were found to be significantly higher in the presence of atazanavir (506 ± 411 vs 177 ± 262 ng/ml).  Of interest, patients with atazanavir AUC0-12 above the mean or with atazanavir concentrations exceeding the half maximal inhibitory concentration for UGT1A1 had higher raltegravir AUCs compared to patients with lower atazanavir exposure.


  1. Zhu L et al. Pharmacokinetics and safety of twice-daily atazanavir 300 mg and raltegravir 400 mg in healthy individuals. Antivir Ther, 2010, 15(8): 1107-14.
  2. Cattaneo D et al. Exposure-related effects of atazanavir on the pharmacokinetics of raltegravir in HIV-1-infected patients. Ther Drug Monit, 2010, 32(6): 782-786.

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