Background: Within this open-label, uncontrolled prospective trial we evaluated safety, efficacy and development of genotypic resistance under the new protease inhibitor lopinavir/ritonavir (LPV/r) in antiretroviral (ARV) HIV patients.
Patients and methods: 58 patients with virological failure under their current ARV therapy were started on a LPV/r containing regimen. Median baseline HIV RNA and CD4 count were 4.6 log(10) cps/ml (range 2.1-6.4) and 128 x 10(6)/l (0-767), respectively. CD4 count, HIV RNA and metabolic parameters were assessed at weeks 0, 4, 8, 12, 16, 24, 32, 40, 48. Genotypic resistance testing was performed at baseline and again at weeks 12, 24 and 48 in the event of virological failure.
Results: Until week 48, viral load (VL) decreased by a median of 1.9 log(10) cps/ml (-0.8-3.8). A VL below 80 cps/ml was found in 20/58 patients (34.5%) at week 48. In parallel, CD4 cells increased to a median of 332 x 10(6)/l (8-905). Nine patients discontinued study treatment. At 48 weeks, median triglyceride and cholesterol levels increased significantly. While the median number of overall protease mutations at baseline was four in all patients, it was six in patients virologically failing on LPV/r. The average number of mutations increased significantly to eight at week 48. Several mutations were detected considerably more often in the event of failure than in response to treatment, e. g. at amino acid positions 10, 24, 54, 71, 82, 84.
Conclusion: LPV/r is effective in heavily pretreated patients. Discontinuation due to adverse events is infrequent. No individual mutation can be associated with failure on LPV/r. However, a greater number of protease mutations at baseline is associated with poorer treatment outcome and several mutations seem to be related to treatment failure.