Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated wi...Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated with hypercholesterolemia and drug interactions. For this study, we examined a dual strategy to manage hypertriglyceridemia in HIV-infected patient taking PIs: 1) switching patients to fosamprenavir (FPV), a PI with fewer drug interactions, and 2) adding prescription fish oil (LOVAZA?), which has been shown to reduce triglycerides. Methods: This multicenter, 24-week study enrolled 36 patients virologically suppressed (HIV-1 RNA <50 copies/mL) on PI-containing therapy with screening triglyceride levels of 200 - 1200 mg/dL and LDL cholesterol levels ≤160 mg/dL. At baseline, patients were switched to ritonavir (RTV)-boosted fosamprenavir (FPV 1400 mg/RTV 100 mg QD) and any lipid-lowering agents were stopped. At Week 6, LOVAZA 4 g QD was added. Results: Five patients prematurely discontinued due to adverse events (2), non-compliance, lost-to-follow up, and protocol violation. Median triglyceride concentration was 303 mg/dL at screening, 262 mg/dL at baseline, 290 mg/dL at Week 6 (+8% from baseline), and 218 mg/dL at Week 24 (–30% from Week 6). At Week 24, 39% (12/31) of patients had triglycerides <200 mg/dL. Among patients reaching Week 24, 100% (31/31) and 90% (28/31) had HIV-1 RNA <400 and <50 copies/mL, respectively. Conclusions: In this study, a switch to FPV/RTV followed by LOVAZA decreased median triglyceride levels and modestly increased the percentage of patients with triglyceride levels <200 mg/dL while maintaining virologic suppression in HIV-infected subjects with hypertriglyceridemia. Our data suggest that baseline PI may affect the likelihood of achieving triglycerides <200 mg/dL after 18 weeks on study. A larger study would be needed to understand the relative contributions of choice of protease inhibitor and LOVAZA to triglyceride concentrations in HIV-infected patients.展开更多
Background: The effect of reducing ritonavir boosting doses on the efficacy and safety of fosamprenavir-based regimens has not been well studied. Methods: In a 52-week, phase 4, open-label, single-center pilot study, ...Background: The effect of reducing ritonavir boosting doses on the efficacy and safety of fosamprenavir-based regimens has not been well studied. Methods: In a 52-week, phase 4, open-label, single-center pilot study, 26 antiretroviral-naive, HIV-infected patients with viral loads >1000 copies/mL received induction with fosamprenavir/ritonavir 1400 mg/200mg plus abacavir/lamivudine 600 mg/300mg once daily for 28 weeks. Patients achieving a viral load 10 copies/mL and CD4+ count 110/mm3. Of 12 induction/maintenance completers, 10 (83%) achieved viral loads 3 at baseline to 292/mm3 at induction-week 28 and to 296/mm3 at maintenance-week 24. The incidence of adverse events at maintenance-week 24 did not differ from that at induction-week 28 (P > 0.05). Median fasting total-cholesterol, LDL-cholesterol, and triglycerides remained below NCEP cut-off levels. Baseline/induction-week 28/maintenance-week 24 median total-cholesterol was 130/177/183 mg/dL, LDL-cholesterol 78/107/114 mg/dL, HDL-cholesterol 33/41/43 mg/dL, total-cholesterol: HDL-cholesterol ratio 3.9/4.3/4.3, and triglycerides 93/145/119 mg/dL. During induction, total VLDL/chylomicron, LDL, and HDL particles increased;during maintenance, VLDL/chylomicron particles decreased, but LDL and HDL particle concentrations did not notably change. Conclusions: Reducing ritonavir boosting from 200 mg to 100 mg once daily in HIV-infected patients stabilized on once-daily fosamprenavir/abacavir/lamivudine resulted in maintenance of virologic suppression, enhanced CD4+ count, and improved triglycerides.展开更多
文摘Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated with hypercholesterolemia and drug interactions. For this study, we examined a dual strategy to manage hypertriglyceridemia in HIV-infected patient taking PIs: 1) switching patients to fosamprenavir (FPV), a PI with fewer drug interactions, and 2) adding prescription fish oil (LOVAZA?), which has been shown to reduce triglycerides. Methods: This multicenter, 24-week study enrolled 36 patients virologically suppressed (HIV-1 RNA <50 copies/mL) on PI-containing therapy with screening triglyceride levels of 200 - 1200 mg/dL and LDL cholesterol levels ≤160 mg/dL. At baseline, patients were switched to ritonavir (RTV)-boosted fosamprenavir (FPV 1400 mg/RTV 100 mg QD) and any lipid-lowering agents were stopped. At Week 6, LOVAZA 4 g QD was added. Results: Five patients prematurely discontinued due to adverse events (2), non-compliance, lost-to-follow up, and protocol violation. Median triglyceride concentration was 303 mg/dL at screening, 262 mg/dL at baseline, 290 mg/dL at Week 6 (+8% from baseline), and 218 mg/dL at Week 24 (–30% from Week 6). At Week 24, 39% (12/31) of patients had triglycerides <200 mg/dL. Among patients reaching Week 24, 100% (31/31) and 90% (28/31) had HIV-1 RNA <400 and <50 copies/mL, respectively. Conclusions: In this study, a switch to FPV/RTV followed by LOVAZA decreased median triglyceride levels and modestly increased the percentage of patients with triglyceride levels <200 mg/dL while maintaining virologic suppression in HIV-infected subjects with hypertriglyceridemia. Our data suggest that baseline PI may affect the likelihood of achieving triglycerides <200 mg/dL after 18 weeks on study. A larger study would be needed to understand the relative contributions of choice of protease inhibitor and LOVAZA to triglyceride concentrations in HIV-infected patients.
文摘Background: The effect of reducing ritonavir boosting doses on the efficacy and safety of fosamprenavir-based regimens has not been well studied. Methods: In a 52-week, phase 4, open-label, single-center pilot study, 26 antiretroviral-naive, HIV-infected patients with viral loads >1000 copies/mL received induction with fosamprenavir/ritonavir 1400 mg/200mg plus abacavir/lamivudine 600 mg/300mg once daily for 28 weeks. Patients achieving a viral load 10 copies/mL and CD4+ count 110/mm3. Of 12 induction/maintenance completers, 10 (83%) achieved viral loads 3 at baseline to 292/mm3 at induction-week 28 and to 296/mm3 at maintenance-week 24. The incidence of adverse events at maintenance-week 24 did not differ from that at induction-week 28 (P > 0.05). Median fasting total-cholesterol, LDL-cholesterol, and triglycerides remained below NCEP cut-off levels. Baseline/induction-week 28/maintenance-week 24 median total-cholesterol was 130/177/183 mg/dL, LDL-cholesterol 78/107/114 mg/dL, HDL-cholesterol 33/41/43 mg/dL, total-cholesterol: HDL-cholesterol ratio 3.9/4.3/4.3, and triglycerides 93/145/119 mg/dL. During induction, total VLDL/chylomicron, LDL, and HDL particles increased;during maintenance, VLDL/chylomicron particles decreased, but LDL and HDL particle concentrations did not notably change. Conclusions: Reducing ritonavir boosting from 200 mg to 100 mg once daily in HIV-infected patients stabilized on once-daily fosamprenavir/abacavir/lamivudine resulted in maintenance of virologic suppression, enhanced CD4+ count, and improved triglycerides.
