Substituting Abacavir for Hyperlipidemia-associated PIs Improves Lipid Profiles, Maintains Virologic Suppression, and Simplifies Treatment

Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. To evaluate this effect, researchers compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL).

Study participants were randomized either to a regimen in which their PI was replaced by abacavir (Ziagen) 300 mg twice daily (n =52) or a regimen in which their PI was continued (n=52) for 28 weeks.

All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naïve to abacavir and non-nucleoside reverse transcriptase inhibitors.

Results

At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively.

At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P<0.001), LDL-cholesterol (-14 vs +5 mg/dL, P =0.016), and triglycerides (-134 vs -36 mg/dL, P =0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P =0.583).

A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades.

At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count.

Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments.

Conclusion

In conclusion, the authors write, “In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.

01/24/05

Reference
P H Keiser and others. Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment BMC Infectious Diseases 5(1): 2-35. January 12, 2005.