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)

AIDS Clinical Trials Group (ACTG) A5257 Team

Aweeka, Francesca

Baugh, Bryan P

Brown, Todd T

Cohn, Susan E

Currier, Judith S

Fischl, Margaret

Godfrey, Catherine

Kuritzkes, Daniel R

Landovitz, Raphael J

Leavitt, Randi Y

Lennox, Jeffrey L

McComsey, Grace A

Na, Lumine H

Ofotokun, Ighovwerha

Para, Michael F

Patterson, Kristine B

Ribaudo, Heather J

Sagar, Manish

Villasis-Keever, Angelina

Clinical Infectious Diseases

PubMed

BackgroundMetabolic 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).MethodsTreatment-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.ResultsAnalyses 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 &gt; .1).ConclusionsRaltegravir 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 registrationNCT 00811954

Ofotokun, Ighovwerha

Na, Lumine H

Landovitz, Raphael J

Ribaudo, Heather J

McComsey, Grace A

Godfrey, Catherine

Aweeka, Francesca

Cohn, Susan E

Sagar, Manish

Kuritzkes, Daniel R

Brown, Todd T

Patterson, Kristine B

Para, Michael F

Leavitt, Randi Y

Villasis-Keever, Angelina

Baugh, Bryan P

Lennox, Jeffrey L

Currier, Judith S

Team, for the AIDS Clinical Trials Group A5257

Saemann, Michelle

Baer, Jennifer

Koletar, Susan

Meixner, Linda

Seefried, Edward

Bailey, Vicki

Basham, Rebecca

Currin, David

Chicurel-Bayard, Miriam

Spitz, Teresa

Frain, Judy

Lindsey, Elizabeth

James, Tamara

Putnam, Beverly

Basler, Cathi

Dube, Michael P

Santos, Bartolo

Daar, Eric

Shaik, Sadia

Tebas, Pablo

Thomas, Aleshia

Bedimo, Roger

Mba, Michelle

Cohn, David

Moran, Fran

Bagur, Jorge L Santana

Dueño, Ileana Boneta

Taiwo, Babafemi

Berzins, Baiba

Chang, Emery

Palmer, Maria

Adams, Mary

Hurley, Christine

Lane, Timothy

Van Dam, Cornelius

Tashima, Karen

Patterson, Helen

del Rio, Carlos

Patrick, Ericka

Markowitz, Norman

Brar, Indira

Arduino, Roberto C

Martinez, Maria Laura

Kim, Rose

Smith, Yolanda

Bolivar, Hector

Fischl, Margaret A

Telzak, Edward

Cindrich, Richard

Sax, Paul

Keenan, Cheryl

Whitely, Kim

Davis, Traci

MacArthur, Rodger D

Farrough, Marti

Aberg, Judith A

Cespedes, Michelle S

Dunaway, Shelia

Storey, Sheryl

Gallant, Joel

Wiggins, Ilene

Sha, Beverly

Navarro, Veronica

Watson, Vicky

Nixon, Daniel

Luetkemeyer, Annie

Dwyer, Jay

Allen, Kristen

Walton, Patricia

Kumar, Princy

Timpone, Joseph

McKellar, Mehri

Granholm, Jacquelin

Yin, Michael T

Torres, Madeline

Valle, Sandra

Slamowitz, Debbie

Davis, Charles E

Blattner, William A

Linus, Benjamin

Albrecht, Mary

eScholarship - University of California

Comparison of the Metabolic Effects of Ritonavir-Boosted Darunavir or Atazanavir Versus Raltegravir, and the Impact of Ritonavir Plasma Exposure: ACTG 5257

Na, Lumine H.

Landovitz, Raphael J.

Ribaudo, Heather J.

Mccomsey, Grace A.

Cohn, Susan E.

Kuritzkes, Daniel R.

Brown, Todd T.

Patterson, Kristine B.

Para, Michael F.

Leavitt, Randi Y.

Baugh, Bryan P.

Lennox, Jeffrey L.

Currier, Judith S.

Carolina Digital Repository

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).
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.
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).
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.
NCT 00811954

University of Miami: Scholarship Miami

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

Comparison of the Metabolic Effects of Ritonavir-Boosted Darunavir or Atazanavir Versus Raltegravir, and the Impact of Ritonavir Plasma Exposure: ACTG 5257

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University of Miami: Scholarship Miami