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Isolated Report of Kaletra Resistance
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Written by David Margolis, M.D.
Dallas VA Medical Center & University of Texas-Southwestern
Primary resistance to lopinavir/ ritonavir (Kaletra) has not been previously reported. Theoretical considerations argue that resistance to this drug is difficult to generate in vivo (in patients).
Steve Deeks (abstr. 70) presented an interesting anecodote showing that under very unusual circumstances genotypic resistance to Kaletra could evolve in vivo. Deeks reported at Tenerife Kaletra resistance developed by one patient showing perhaps that resistance can develop. Initially treated with a standard regimen, resulting in suppression to < 75 copies, this subject was then switched to therapy containing Kaletra. The patient then stopped taking his backgrounds medicines and took Kaletra monotherapy for a year before reappearing in clinic. It appeared that the patient may not have been adherent but this was not substantiated. Viral rebound had occurred (>14,000 copies/ml) with genotype showing an unusual mutation at I47A, with V32I and M46M/I mutations in protease. Phenotypic resistance to lopinavir (FC 38) and low RC (2.9%), with susceptibility to all other PIs was seen. The I47A mutation has been selected in lab passage experiments in the past, but is seen in only 0.08% of samples in the ViroLogic database after the approval of Kaletra. It appears to be a favored pathway of solo lopinavir resistance, but may be highly disfavored in the setting of combination therapy.
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