The rabbit study: Ritonavir and saquinavir in combination in saquinavir-experienced and previously untreated patients

Thirteen protease inhibitor-naive patients with HIV-1 infection, and 12 pat ients with a median of 58 months prior treatment with saquinavir (SQV) mono therapy, were treated with SQV (400 mg twice daily) and ritonavir (RIT, 500 mg twice daily) in a study designed to assess the effect of prior treatmen t with SQV monotherapy on the antiretroviral activity of RIT-SQV combinatio n therapy. Median baseline viral load and CD4(+) cell counts mere 155,000 a nd 262,000 copies/ml and 333 and 225 cells/mm(3) in the naive and experienc ed groups, respectively. Mean viral load changes at 24 weeks were -1.63 and -0.27 log copies/ml in the naive and SQV-experienced groups, respectively (intent-to-treat analysis). Baseline genotype by point mutation assay and s equencing in the SQV-experienced group was highly predictive of virological response. Eight of 11 SQV-experienced patients had evidence of phenotypic resistance to RIT at baseline, despite previous treatment with SQV only. Th ere was strong correlation between phenotypic resistance to RIT and the pre sence of the L90M mutation. We conclude that prolonged prior treatment with saquinavir monotherapy may produce cross-resistance to ritonavir and reduc e the subsequent response to ritonavir-saquinavir in combination. In this s tudy, both phenotypic resistance to ritonavir and presence of the L90M muta tion predicted the viral load response to ritonavir-saquinavir.