Overcoming Resistance: Virologic Response to a Salvage Regimen with the Combination of Ritonavir plus Indinavir

Abstract

Purpose: To explore the possibility of overcoming resistance to protease inhibitors (PIs) and to determine the resistance cutoff values that continue to predict treatment failure with a dual PI regimen. Method: We performed a prospective study of 53 patients who had failed in several PIs and who were included in a ritonavir (RTV) plus indinavir (IDV) salvage regimen. Median HIV RNA level decrease was evaluated according to resistance assays and indinavir trough levels. Results: Eighty-seven percent of patients had previously failed on an IDV-containing regimen. Overall, median HIV RNA decrease was –1.25 log₁₀ copies/mL after 3 months on therapy. A significant blunted virologic response was observed only in isolates with more than 12 substitutions including the V82A (–0.75 vs. –1.3 log₁₀ copies/mL; p = .04), or in isolates with more than 30 fold-increase in the IC₅₀ (–0.43 vs. –1.2 log₁₀ copies/mL). Higher drug levels were observed in patients with resistant isolates who achieved an HIV RNA decrease greater than 1 log (1742 vs. 1100 ng/mL). Conclusion: Our preliminary data suggest the possibility of overcoming resistance with the combination of RTV plus IDV. They also suggest the need for establishing new resistance cutoff values when using PIs in combination.

Keywords:

• pharmacokinetics
• protease inhibitors
• resistance