Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257
Ighovwerha Ofotokun, Lumine H Na, Raphael J Landovitz, Heather J Ribaudo, Grace A McComsey, Catherine Godfrey, Francesca Aweeka, Susan E Cohn, Manish Sagar, Daniel R Kuritzkes, Todd T Brown, Kristine B Patterson, Michael F Para, Randi Y Leavitt, Angelina Villasis-Keever, Bryan P Baugh, Jeffrey L Lennox, Judith S Currier, AIDS Clinical Trials Group (ACTG) A5257 Team, Michelle Saemann, Jennifer Baer, Susan Koletar, Linda Meixner, Edward Seefried, Vicki Bailey, Rebecca Basham, David Currin, Miriam Chicurel-Bayard, Teresa Spitz, Judy Frain, Elizabeth Lindsey, Tamara James, Beverly Putnam, Cathi Basler, Michael P Dube, Bartolo Santos, Eric Daar, Sadia Shaik, Pablo Tebas, Aleshia Thomas, Roger Bedimo, Michelle Mba, David Cohn, Fran Moran, Jorge L Santana Bagur, Ileana Boneta Dueño, Babafemi Taiwo, Baiba Berzins, Emery Chang, Maria Palmer, Mary Adams, Christine Hurley, Timothy Lane, Cornelius Van Dam, Karen Tashima, Helen Patterson, Carlos Del Rio, Ericka Patrick, Norman Markowitz, Indira Brar, Roberto C Arduino, Maria Laura Martinez, Rose Kim, Yolanda Smith, Hector Bolivar, Margaret A Fischl, Edward Telzak, Richard Cindrich, Paul Sax, Cheryl Keenan, Kim Whitely, Traci Davis, Rodger D MacArthur, Marti Farrough, Judith A Aberg, Michelle S Cespedes, Shelia Dunaway, Sheryl Storey, Joel Gallant, Ilene Wiggins, Beverly Sha, Veronica Navarro, Vicky Watson, Daniel Nixon, Annie Luetkemeyer, Jay Dwyer, Kristen Allen, Patricia Walton, Princy Kumar, Joseph Timpone, Mehri McKellar, Jacquelin Granholm, Michael T Yin, Madeline Torres, Sandra Valle, Debbie Slamowitz, Charles E Davis, William A Blattner, Benjamin Linus, Mary Albrecht, Christina Megill, Valery Hughes, Teri Flynn, Amy Sbrolla, Sharon Riddler, Lisa Klevens, Ighovwerha Ofotokun, Lumine H Na, Raphael J Landovitz, Heather J Ribaudo, Grace A McComsey, Catherine Godfrey, Francesca Aweeka, Susan E Cohn, Manish Sagar, Daniel R Kuritzkes, Todd T Brown, Kristine B Patterson, Michael F Para, Randi Y Leavitt, Angelina Villasis-Keever, Bryan P Baugh, Jeffrey L Lennox, Judith S Currier, AIDS Clinical Trials Group (ACTG) A5257 Team, Michelle Saemann, Jennifer Baer, Susan Koletar, Linda Meixner, Edward Seefried, Vicki Bailey, Rebecca Basham, David Currin, Miriam Chicurel-Bayard, Teresa Spitz, Judy Frain, Elizabeth Lindsey, Tamara James, Beverly Putnam, Cathi Basler, Michael P Dube, Bartolo Santos, Eric Daar, Sadia Shaik, Pablo Tebas, Aleshia Thomas, Roger Bedimo, Michelle Mba, David Cohn, Fran Moran, Jorge L Santana Bagur, Ileana Boneta Dueño, Babafemi Taiwo, Baiba Berzins, Emery Chang, Maria Palmer, Mary Adams, Christine Hurley, Timothy Lane, Cornelius Van Dam, Karen Tashima, Helen Patterson, Carlos Del Rio, Ericka Patrick, Norman Markowitz, Indira Brar, Roberto C Arduino, Maria Laura Martinez, Rose Kim, Yolanda Smith, Hector Bolivar, Margaret A Fischl, Edward Telzak, Richard Cindrich, Paul Sax, Cheryl Keenan, Kim Whitely, Traci Davis, Rodger D MacArthur, Marti Farrough, Judith A Aberg, Michelle S Cespedes, Shelia Dunaway, Sheryl Storey, Joel Gallant, Ilene Wiggins, Beverly Sha, Veronica Navarro, Vicky Watson, Daniel Nixon, Annie Luetkemeyer, Jay Dwyer, Kristen Allen, Patricia Walton, Princy Kumar, Joseph Timpone, Mehri McKellar, Jacquelin Granholm, Michael T Yin, Madeline Torres, Sandra Valle, Debbie Slamowitz, Charles E Davis, William A Blattner, Benjamin Linus, Mary Albrecht, Christina Megill, Valery Hughes, Teri Flynn, Amy Sbrolla, Sharon Riddler, Lisa Klevens
Abstract
Background: Metabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma ritonavir trough concentrations (C24).
Methods: Treatment-naive adult subjects were randomized to ritonavir-boosted atazanavir or darunavir, or raltegravir-based cART. Changes in lipids and other metabolic outcomes over time were estimated. Differences between arms were estimated with 97.5% confidence intervals and compared using pairwise Student t tests. Associations between ritonavir C24 and lipid changes at week 48 were evaluated via linear regression.
Results: Analyses included 1797 subjects with baseline fasting data. Baseline lipid profiles and metabolic syndrome rates (approximately 21%) were similar across arms. Comparable increases occurred in total cholesterol, triglycerides, and low-density lipoprotein cholesterol with the boosted protease inhibitors (PIs); each PI had greater increases relative to raltegravir (all P ≤ .001 at week 96). Metabolic syndrome incident rates by week 96 (approximately 22%) were not different across arms. Ritonavir C24 was not different by arm (P = .89) (median, 69 ng/mL and 74 ng/mL in the atazanavir and darunavir arms, respectively) and were not associated with changes in lipid measures (all P > .1).
Conclusions: Raltegravir produced the most favorable lipid profile. Metabolic syndrome rates were high at baseline and increased to the same degree in all arms. Ritonavir C24 was not different in the PI arms and had no relationship with the modest but comparable increases in lipids observed with either atazanavir or darunavir. The long-term clinical significance of the lipid changes noted with the PIs relative to raltegravir deserves further evaluation.
Clinical trials registration: NCT 00811954.
Trial registration: ClinicalTrials.gov NCT00811954.
Keywords: HIV/AIDS; cART; lipids; metabolic syndrome.
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Source: PubMed