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The concept of PI boosting
Pharmacokinetic enhancement or �boosting�, whereby pharmacokinetic interactions between the PIs and a second agent are exploited to raise PI exposure, aims to provide more predictable PI exposures and improve the dosing. Benefits of this approach may include:
- Reductions in the frequency of dosing
- Decreased pill count (and, potentially, a subsequent decrease in the cost of therapy)
- Limitation of non-nucleoside reverse transcriptase inhibitor (NNRTI)-induced drug interactions
- Reduced restrictions with respect to administration of the PI with food22
- Higher plasma levels of PI may also increase the potential to suppress resistant viral strains23
How is PI boosting achieved?
PI boosting is achieved by administering a second agent (most frequently low-dose ritonavir) with the PI
Currently, in clinical trials, lower doses of ritonavir than those approved for the treatment of HIV-1 infection19 (e.g. 100�400 mg given once- or twice-daily) have been administered with the PIs (Table 2) to improve their pharmacokinetic profile
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'Boosted PI' |
Doses frequently studied |
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Saquinavir/ritonavir
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1600 mg/100 mg once-daily24,25
1000 mg/100 mg twice-daily26
400 mg/400 mg twice-daily27,28 |
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Lopinavir/ritonavir |
400 mg/100 mg twice-daily29,30,31
533 mg/133 mg twice-daily32 |
| Indinavir/ritonavir |
800 mg/100 mg twice-daily7,33
800 mg/200 mg twice-daily34
400 mg/400 mg twice-daily34
1200 mg/200 mg once-daily35
1200 mg/400 mg once-daily35 |
| Amprenavir/ritonavir |
600 mg/100 mg twice-daily36
600 mg/200 mg twice-daily37
1200 mg/200 mg once-daily36 |
Table 2. Examples of boosted PIs in clinical trials.
- Although ritonavir is by far the most frequently employed agent for pharmacokinetic enhancement, the NNRTI delavirdine has been shown to successfully increase the exposure to PIs including saquinavir,38 indinavir,39 amprenavir40 and nelfinavir.41 Other drugs that may increase PI exposure include ketoconazole and milk thistle
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