BACKGROUND: The metabolic effects of initial therapy for HIV-1 infection are important determinants of regimen selection. METHODS: Open-label study in 753 subjects randomized equally toefavirenz 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. RESULTS: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. CONCLUSION: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.
RCT Entities:
BACKGROUND: The metabolic effects of initial therapy for HIV-1 infection are important determinants of regimen selection. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Don E Smith; Jeff Hudson; Allison Martin; Judith Freund; Matthew R Griffiths; Sue Kalnins; Matthew Law; Andrew Carr; David A Cooper Journal: HIV Clin Trials Date: 2003 Jan-Feb
Authors: K A Lichtenstein; D J Ward; A C Moorman; K M Delaney; B Young; F J Palella; P H Rhodes; K C Wood; S D Holmberg Journal: AIDS Date: 2001-07-27 Impact factor: 4.177
Authors: M P Dubé; D Sprecher; W K Henry; J A Aberg; F J Torriani; H N Hodis; J Schouten; J Levin; G Myers; R Zackin; T Nevin; J S Currier Journal: Clin Infect Dis Date: 2000-11-07 Impact factor: 9.079
Authors: Joel E Gallant; Schlomo Staszewski; Anton L Pozniak; Edwin DeJesus; Jamal M A H Suleiman; Michael D Miller; Dion F Coakley; Biao Lu; John J Toole; Andrew K Cheng Journal: JAMA Date: 2004-07-14 Impact factor: 56.272
Authors: E Fontas; F van Leth; C A Sabin; N Friis-Møller; M Rickenbach; A d'Arminio Monforte; O Kirk; M Dupon; L Morfeldt; S Mateu; K Petoumenos; W El-Sadr; S de Wit; J D Lundgren; C Pradier; P Reiss Journal: J Infect Dis Date: 2004-03-02 Impact factor: 5.226
Authors: Nina Friis-Møller; Caroline A Sabin; Rainer Weber; Antonella d'Arminio Monforte; Wafaa M El-Sadr; Peter Reiss; Rodolphe Thiébaut; Linda Morfeldt; Stephane De Wit; Christian Pradier; Gonzalo Calvo; Matthew G Law; Ole Kirk; Andrew N Phillips; Jens D Lundgren Journal: N Engl J Med Date: 2003-11-20 Impact factor: 91.245
Authors: Todd Hulgan; Richard Haubrich; Sharon A Riddler; Pablo Tebas; Marylyn D Ritchie; Grace A McComsey; David W Haas; Jeffrey A Canter Journal: AIDS Date: 2011-01-02 Impact factor: 4.177
Authors: Philip M Grant; Douglas Kitch; Grace A McComsey; Ann C Collier; Benedetta Bartali; Susan L Koletar; Kristine M Erlandson; Jordan E Lake; Michael T Yin; Kathy Melbourne; Belinda Ha; Todd T Brown Journal: AIDS Date: 2016-11-28 Impact factor: 4.177
Authors: Steve Innes; Eva Schulte-Kemna; Mark F Cotton; Ekkehard Werner Zöllner; Richard Haubrich; Hartwig Klinker; Xiaoying Sun; Sonia Jain; Clair Edson; Margaret van Niekerk; Emily Ryan Innes; Helena Rabie; Sara H Browne Journal: Pediatr Infect Dis J Date: 2013-06 Impact factor: 2.129