Salvage Treatment with Lopinavir/Ritonavir (Kaletra) in HIV-Infected Patients Failing All Current Antiretroviral Drug Families

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Abstract
Lopinavir/ritonavir (Kaletra) is the latest available protease inhibitor (PI). It has shown greater potency than the former PIs in phase II/III trials, either in naive or in PI-experienced patients being naive for nonnucleoside reverse transcriptase inhibitors (NNRTIs). We analyzed the first 138 patients recruited during the expanded access program in an HIV/AIDS reference center. Only patients who had significant past exposure to all three different antiretroviral drug families and who were failing their current regimens were chosen. A total of 93 and 76 patients completed, respectively, 3 and 6 months of follow-up. Mean plasma HIV RNA log(10) copies/mL before beginning Kaletra was 4.04 +/- 1.1 and mean CD4 count was 285 +/- 197 cells/mL. Overall, 76.3% and 63.2% of patients showed a significant virologic response (defined as >1 log reduction in plasma HIV RNA and/or a reduction to less than 500 HIV RNA copies/mL) at 3 and 6 months, respectively. The mean CD4 increase was +77.3 cells/mL at 6 months. Thirteen individuals did not complete 6 months on therapy: there were 2 deaths (1 was non-AIDS related), 2 patients were lost to follow-up, 7 patients withdrew due to potential drug adverse events, and 2 patients withdrew due to complications of intercurrent illnesses. Triglyceride levels significantly increased 3 months after initiation of Kaletra (+70 mg/dL; p =.04) while cholesterol levels remained stable (+7.7 mg/dL; p =.7). Sequence analysis at baseline showed a median number of PI mutations of 4 (0 to 12). Overall, 45% of patients harbored >/=5 PI mutations. Attainment of plasma HIV RNA 5 PI mutations (p <.001). Baseline mutations at codons 71 and 82 were associated with a lower response to Kaletra. Kaletra is relatively well tolerated and provides potent antiviral activity in heavily pretreated patients. Significant virological responses are seen in more than three quarters of patients at 3 months. Genotyping at the time of initiation of salvage therapy with Kaletra might help to predict which individuals will experience a greater benefit.