Ighovwerha Ofotokun1, Lumine H Na2, Raphael J Landovitz3, Heather J Ribaudo2, Grace A McComsey4, Catherine Godfrey5, Francesca Aweeka6, Susan E Cohn7, Manish Sagar8, Daniel R Kuritzkes9, Todd T Brown10, Kristine B Patterson11, Michael F Para12, Randi Y Leavitt13, Angelina Villasis-Keever14, Bryan P Baugh15, Jeffrey L Lennox1, Judith S Currier3. 1. Grady Memorial Hospital and Emory University School of Medicine, Atlanta, Georgia. 2. Harvard School of Public Health, Boston, Massachusetts. 3. Division of Infectious Diseases, Center for Clinical AIDS Research and Education, University of California, Los Angeles. 4. Case Western Reserve University, Cleveland, Ohio. 5. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 6. University of California, San Francisco School of Pharmacy. 7. Northwestern University Feinberg School of Medicine, Chicago, Illinois. 8. School of Medicine, Boston University. 9. Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 10. Johns Hopkins University, Baltimore, Maryland. 11. University of North Carolina School of Medicine, Chapel Hill. 12. The Ohio State University College of Medicine, Columbus. 13. Merck & Co, Inc, Whitehouse Station, New Jersey. 14. Bristol-Myers Squibb, New York, New York. 15. Janssen Scientific Affairs, LLC, Titusville, New Jersey.
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.
RCT Entities:
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.
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