Efficacy of a five-drug combination including ritonavir, saquinavir and efavirenz in patients who failed on a conventional triple-drug regimen: phenotypic resistance to protease inhibitors predicts outcome of therapy

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Abstract

Objective:

to assess the safety and efficacy of a combination of ritonavir, efavirenz and two recycled nucleosides in patients who failed on a conventional triple-drug regimen including indinavir or ritonavir.

Methods:

An open label study of ritonavir (100mg twice daily), saquinavir (1000mg twice daily), efavirenz (600mg per day) and nucleoside analogues in 32 saquinavir- and efavirenz-naive protease inhibitor-experienced patients. Patients were included on the basis of plasma levels of HIV RNA above 5000copies/ml while on conventional antiretroviral therapy. Phenotypic resistance and genotypic resistance mutations to saquinavir were assessed at baseline. Peak and trough plasma levels of saquinavir were monitored throughout the study.

Results:

Median CD4 cell counts and median plasma HIV RNA at baseline were 258×106/l and 4.31 log10 copies/ml, respectively. The plasma viral load decreased by a median of 1.20 log10 copies/ml and the CD4 cell count increased by a median 60×106cells/l at week 24 of therapy. Seventy-one per cent of the patients achieved a plasma viral load <500copies/ml and 45% achieved a viral load <50copies/ml. Patients exhibiting phenotypic resistance to saquinavir at baseline experienced a median decrease in HIV RNA of 0.91 log10 copies/ml at week 24 of therapy, as compared with a decrease of 1.52log10 copies/ml in those exhibiting sensitive viral strains (P=0.03). Genotypic resistance to saquinavir was not predictive of virologic failure.

Conclusion:

Our results indicate that the combination of ritonavir, saquinavir and efavirenz is safe and effective at 24 weeks in over two-thirds of patients who previously failed on highly active antiretroviral therapy, and that the determination of phenotypic resistance may be of greater value than the detection of resistance mutations to predict the outcome of salvage therapy in this setting.

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