Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment

• Published in: AIDS (London) Vol. 23; no. 9; pp. 1109 - 1118
• Main Authors: Haubrich, Richard H, Riddler, Sharon A, DiRienzo, A Gregory, Komarow, Lauren, Powderly, William G, Klingman, Karin, Garren, Kevin W, Butcher, David L, Rooney, James F, Haas, David W, Mellors, John W, Havlir, Diane V
• Format: Journal Article
• Language: English
• Published: England 01.06.2009
• Subjects: Absorptiometry, Photon; Adult; Alkynes; Benzoxazines - administration & dosage; Benzoxazines - adverse effects; Cyclopropanes; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV-1; HIV-Associated Lipodystrophy Syndrome - chemically induced; HIV-Associated Lipodystrophy Syndrome - metabolism; Human immunodeficiency virus 1; Humans; Lipid Metabolism - drug effects; Lopinavir; Male; Pyrimidinones - administration & dosage; Pyrimidinones - adverse effects; Ritonavir - administration & dosage; Ritonavir - adverse effects
• ISSN: 0269-9370; 1473-5571; 1473-5571
• DOI: 10.1097/QAD.0b013e32832b4377

The metabolic effects of initial therapy for HIV-1 infection are important determinants of regimen selection. Open-label study in 753 subjects randomized equally to efavirenz or lopinavir/ritonavir(r) plus two nucleoside reverse-transcriptase inhibitor (NRTI) vs. the NRTI-sparing regimen of lopinavir/r plus efavirenz. Zidovudine, stavudine, or tenofovir with lamivudine was selected prior to randomization. Metabolic outcomes through 96 weeks were lipoatrophy, defined as at least 20% loss in extremity fat, and fasting serum lipids. Lipoatrophy by dual-energy X-ray absorptiometry at week 96 occurred in 32% [95% confidence interval (CI) 25-39%] of subjects in the efavirenz plus two NRTIs arm, 17% (95% CI 12-24) in the lopinavir/r plus two NRTIs arm, and 9% (95% CI 5-14) in the NRTI-sparing arm (P < or = 0.023 for all comparisons). Varying the definition of lipoatrophy (> or =10 to > or =40% fat loss) and correction for baseline risk factors did not affect the significant difference in lipoatrophy between the NRTI-containing regimens. Lipoatrophy was most frequent with stavudine-containing regimens and least frequent with tenofovir-containing regimens (P < 0.001), which were not significantly different from the NRTI-sparing regimen. Total cholesterol increases at week 96 were greatest in the NRTI-sparing arm (median +57 mg/dl) compared with the other two arms (+32-33 mg/dl; P < 0.001). Use of lipid-lowering agents was more common (25 vs. 11-13%) in the NRTI-sparing arm. Lipoatrophy was more frequent with efavirenz than lopinavir/r when combined with stavudine or zidovudine, and less frequent when either drug was combined with tenofovir. Lipoatrophy was least frequent with the NRTI-sparing regimen, but this benefit was offset by greater cholesterol elevations and the need for lipid-lowering agents.