Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment

• Published in: BMC infectious diseases Vol. 5; no. 1; p. 2
• Main Authors: Keiser, Philip H, Sension, Michael G, DeJesus, Edwin, Rodriguez, Allan, Olliffe, Jeffrey F, Williams, Vanessa C, Wakeford, John H, Snidow, Jerry W, Shachoy-Clark, Anne D, Fleming, Julie W, Pakes, Gary E, Hernandez, Jaime E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.01.2005; BioMed Central; BMC
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active - methods; Cholesterol - blood; Cholesterol - classification; Dideoxynucleosides - administration & dosage; Dideoxynucleosides - pharmacology; Dideoxynucleosides - therapeutic use; Female; HIV Infections - complications; HIV Infections - drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV-1 - drug effects; HIV-1 - isolation & purification; Human immunodeficiency virus 1; Humans; Hyperlipidemias - chemically induced; Hyperlipidemias - prevention & control; Least-Squares Analysis; Lipids - blood; Male; Middle Aged; Pilot Projects; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Triglycerides - blood; Triglycerides - classification
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/1471-2334-5-2

Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. An open-label, randomized pilot study 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) who were randomized either to a regimen in which their PI was replaced by abacavir 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 naive to abacavir and non-nucleoside reverse transcriptase inhibitors. 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. 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.