This regimen is also more convenient than other saquinavir-containing regimens, which now require that the patient take six capsules of saquinavir three times daily. Switching when the viral load is low may minimize the number of mutations that lead to cross-resistance. These findings are consistent with what is known about genotypic patterns of NFV resistance, which is typically heralded by the development of the D30N mutation, a mutation which by itself does not lead to decreased susceptibility to other protease inhibitors. NFV increases the AUC of SQV by 5-fold, while SQV has no effect on NFV levels. RTV may also accentuate the M8 metabolite of NFV, possibly resulting in increased antiviral activity.
Pharmacokinetic studies are in progress.
A multidose pharmacokinetic study of this combination demonstrated that IDV clearance is reduced by RTV, which leads to less variability in pharmacokinetics and increased trough levels. Efficacy data are not available for this combination. The same was true when the dose of NFV was increased to 1000 mg bid. Efficacy was disappointing, perhaps because of inadequate drug levels. Until appropriate dosing can be worked out, this combination should probably be avoided in clinical practice.