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

Objective: to assess the safety and efficacy of a combination of ritonavir, efavirenz and two recycled nucleosides in patients who failed on a convent ional triple-drug regimen including indinavir or ritonavir. Methods: An open label study of ritonavir (100 mg twice daily), saquinavir (1000 mg twice daily), efavirenz (600 mg per day) and nucleoside analogues in 32 saquinavir- and efavirenz-naive protease inhibitor,experienced patien ts. Patients were included on the basis of plasma levels of HIV RNA above 5 000 copies/ml while on conventional antiretroviral therapy. Phenotypic resi stance and genotypic resistance mutations to saquinavir were assessed at ba seline. Peak and trough plasma levels of saquinavir were monitored througho ut the study. Results: Median CD4 cell counts and median plasma HIV RNA at baseline were 258 x 10(6)/l and 4.31 log(10) copies/ml, respectively. The plasma viral lo ad decreased by a median of 1.20 log(10) copies/ml and the CD4 cell count i ncreased by a median 60 x 10 cells/l at week 24 of therapy. Seventy-one per cent of the patients achieved a plasma viral load < 500 copies/ml and 45% achieved a viral load < 50 copies/ml. Patients exhibiting phenotypic resist ance to saquinavir at baseline experienced a median decrease in HIV RNA of 0.91 log(10) copies/ml at week 24 of therapy, as compared with a decrease o f 1.52 log(10) copies/ml in those exhibiting sensitive viral strains (P = 0 .03). Genotypic resistance to saquinavir was not predictive of virologic fa ilure. Conclusion: Our results indicate that the combination of ritonavir, saquina vir and efavirenz is safe and effective at 24 weeks in over two-thirds of p atients who previously failed on highly active antiretroviral therapy, and that the determination of phenotypic resistance may be of greater value tha n the detection of resistance mutations to predict the outcome of salvage t herapy in this setting. (C) 1999 Lippincott Williams & Wilkins.