Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257.

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.

• Authors: 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
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 60 Issue 12 Pg. 1842-51 (06 15 2015) ISSN: 1537-6591 [Electronic] United States
• PMID: 25767256 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © 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: [email protected].

Chemical References

• Anti-HIV Agents
• Blood Glucose
• Lipids
• Raltegravir Potassium
• Atazanavir Sulfate
• Ritonavir
• Darunavir

Topics

• Adult
• Anti-HIV Agents (administration & dosage, pharmacology, therapeutic use)
• Atazanavir Sulfate (administration & dosage, pharmacology, therapeutic use)
• Blood Glucose (drug effects)
• Darunavir (administration & dosage, pharmacology, therapeutic use)
• Drug Therapy, Combination
• Female
• HIV Infections (drug therapy, metabolism)
• HIV-1
• Humans
• Lipids (blood)
• Male
• Raltegravir Potassium (administration & dosage, pharmacology, therapeutic use)
• Ritonavir (administration & dosage, pharmacology, therapeutic use)