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Clinical Trial
. 2015 Jun 15;60(12):1842-51.
doi: 10.1093/cid/civ193. Epub 2015 Mar 12.

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

Ighovwerha Ofotokun  1 , Lumine H Na  2 , Raphael J Landovitz  3 , Heather J Ribaudo  2 , Grace A McComsey  4 , Catherine Godfrey  5 , Francesca Aweeka  6 , Susan E Cohn  7 , Manish Sagar  8 , Daniel R Kuritzkes  9 , Todd T Brown  10 , Kristine B Patterson  11 , Michael F Para  12 , Randi Y Leavitt  13 , Angelina Villasis-Keever  14 , Bryan P Baugh  15 , Jeffrey L Lennox  1 , Judith S Currier  3 ; AIDS Clinical Trials Group (ACTG) A5257 Team
Collaborators, Affiliations
Clinical Trial

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

Ighovwerha Ofotokun et al. Clin Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Mean changes from baseline in metabolic outcomes and anthropometric measures, over time, with 95% confidence interval. Abbreviations: ATV/RTV, ritonavir-boosted atazanavir; Diff, difference; DRV/RTV, ritonavir-boosted darunavir; LDL-C, low-density lipoprotein cholesterol; RAL, raltegravir.
Figure 2.
Figure 2.
Cumulative probability of metabolic syndrome, by treatment group. A total of 1363 subjects were included in this analysis; 381 subjects who had metabolic syndrome at baseline and 53 subjects who were censored at baseline were excluded. Abbreviations: ATV/RTV, ritonavir-boosted atazanavir; DRV/RTV, ritonavir-boosted darunavir; RAL, raltegravir.
See this image and copyright information in PMC

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