Background: 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).
Method: 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.
Results: 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 <500 copies/mL occurred in 88% of patients with </=5 PI mutations but only in 48% of those harboring >5 PI mutations (p <.001). Baseline mutations at codons 71 and 82 were associated with a lower response to Kaletra.
Conclusion: 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.