Impact of Antiretroviral Therapy on Metabolic, Skeletal, and Cardiovascular Parameters

Cardiovascular, Anthropometric, and Skeletal Effects of Antiretroviral Therapy (ART) Initiation With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Plus Atazanavir/Ritonavir (ATV/r), Darunavir/Ritonavir (DRV/r), or Raltegravir (RAL): Metabolic Substudy of A5257

The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV-infected people who have never received anti-HIV therapy be treated with a triple drug regimen (commonly called combination antiretroviral therapy, cART). Since the introduction of cART, morbidity and mortality among HIV-infected patients has been dramatically reduced. However, metabolic, skeletal, and cardiovascular diseases have been increasingly reported among HIV-infected patients and may be attributable, in part, to the direct effects of cART. Much of our understanding of the development of these diseases, risk factors, and consequences of these disorders has been derived from clinical studies of HIV-infected persons receiving older antiretroviral agents.

A5260s was designed to examine the contributions of HIV-disease related factors and impact of newer antiretroviral drugs on the development of metabolic (such as blood vessels, blood sugar, cholesterol), skeletal, and cardiovascular diseases in people who have never received anti-HIV therapy. A5260s is a prospective substudy of a phase III randomized clinical trial A5257 (see ClinicalTrials.gov identifier: NCT00811954). A5257 was designed to look at different combinations of anti-HIV drugs that do not contain the medication efavirenz (EFV) and how well these drug combinations work to decrease the amount of HIV in the blood and to allow immune system recovery in people who have never received anti-HIV therapy. A5257 also examined drug tolerability and safety for the various drug combinations.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Ritonavir; Drug: Atazanavir; Drug: Raltegravir; Drug: Darunavir

Detailed Description

A5260s is the optional, metabolic substudy of a phase III, prospective, randomized clinical trial (A5257). For complete details about the parent study A5257, please see ClinicalTrials.gov identifier NCT00811954.

Some participants in study A5257 were asked to participate in substudy A5260s. Not all participants were asked since A5260s only took place at a subset of A5257 sites. Participants who agreed to participate in substudy A5260s were enrolled at the same time as their enrollment in A5257. No interventions were given as part of A5260s, but all A5260s participants underwent blood draws, self-administered questionnaire responses (related to physical activity and body image), ultrasound scans to measure the thickness of the carotid artery in the neck and brachial artery flow mediated dilation in the arm, and computerized topography (CT) and dual-energy x-ray absorptiometry (DEXA) scans to measure bone mineral density and body fat.

The duration of A5260s study was between 2 and 3 years (96 and 144 weeks), depending on when the participant enrolled. The study was designed to enroll a total of 330 participants with at least 110 per a group; each group represented a different randomized drug combination as defined and assigned by the main study A5257.

Cohort A: Atazanavir (ATV) + Ritonavir (RTV) + Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)

Cohort B: Raltegravir (RAL) + FTC/TDF

Cohort C: Darunavir (DRV) + RTV + FTC/TDF

All participants were asked to return for A5260s clinic visits at weeks 4, 24, 48 96 and 144 and participated in all clinical evaluations. No clinical evaluation was restricted to a subset of A5260s participants. If a participant chose to discontinue participation in the substudy, the participant was able to continue in study A5257. However, a participant discontinuing participation from A5257 was also removed from A5260s. Additionally, a participant's decision to discontinue or switch study drugs in the main study did not impact participation and follow-up clinic visits in A5260s.

• Study Type: Observational
• Enrollment (Actual): 334

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC CRS
    • Los Angeles, California, United States, 90035
      • UCLA CARE Center CRS
    • San Francisco, California, United States, 94110
      • Ucsf Aids Crs
    • Torrance, California, United States, 90502
      • Harbor - UCLA Med. Ctr. CRS
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS (6101)
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • The Ponce de Leon Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS (2701)
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center (2702)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Adult AIDS CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med. Ctr., ACTG CRS
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hosp. ACTG CRS
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University CRS (2101)
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School- Adult Clinical Research Ctr. CRS
  • New York
    • New York, New York, United States, 10016
      • NY Univ. HIV/AIDS CRS (401)
    • Rochester, New York, United States, 14607
      • AIDS Care CRS
    • Rochester, New York, United States, 14642
      • University of Rochester ACTG CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Unc Aids Crs
    • Durham, North Carolina, United States, 27710
      • Duke Univ. Med. Ctr. Adult CRS (1601)
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati CRS (2401)
    • Cleveland, Ohio, United States, 44106
      • Case CRS
    • Cleveland, Ohio, United States, 44109
      • Metro Health CRS
    • Colombus, Ohio, United States, 43210
      • The Ohio State University AIDS CRS (2301)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pitt CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Therapeutics CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS (31473)
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington AIDS CRS (1401)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Antiretroviral naïve, HIV-infected men and women with HIV-1 RNA level >1000 copies/ml initiating treatment for HIV-1 infection.

Description

Inclusion Criteria:

• Enrollment in A5257 and intent to enroll in A5001 (ALLRT)
• Signed informed consent
• For A5257 inclusion criteria, please see ClinicalTrials.gov identifier NCT00811954

Exclusion Criteria:

• Diabetes mellitus, (fasting plasma glucose ≥ 126 mg/dL on two occasions or on hypoglycemic medications).
• Known cardiovascular disease (history of myocardial infarction [MI], coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, or peripheral arterial disease with ankle-brachial index of less than 0.9 or claudication)
• Uncontrolled hypothyroidism or hyperthyroidism which in the opinion of the site investigator would affect substudy participation
• Current use of statins, fish oil (greater than 2 grams per day), fibric acid derivatives, or niacin (more than 1000 mg per day) (NOTE: Current use of fish oil and niacin is defined as receiving treatment in the 8 weeks prior to study entry)
• Intention to start pharmacological or surgical intervention for weight loss
• Use of any ART in the 30 days before study entry
• For A5257 exclusion criteria, please see ClinicalTrials.gov identifier NCT00811954

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; ATV/RTV + FTC/TDF Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.	Drug: Emtricitabine/tenofovir disoproxil fumarate; 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs). Other Name: TDF/FTC; Drug: Ritonavir; 100 mg taken orally once daily. A protease inhibitor (PI). Other Name: RTV; Drug: Atazanavir; 300 mg taken orally once daily. A protease inhibitor (PI). Other Name: ATV
Cohort B; RAL + FTC/TDF FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.	Drug: Emtricitabine/tenofovir disoproxil fumarate; 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs). Other Name: TDF/FTC; Drug: Ritonavir; 100 mg taken orally once daily. A protease inhibitor (PI). Other Name: RTV; Drug: Raltegravir; 400 mg taken orally twice daily. An integrase inhibitor (INI). Other Name: RAL
Cohort C; DRV/RTV + FTC/TDF FTC/TDF, darunavir (DRV), and RTV, orally, once daily.	Drug: Emtricitabine/tenofovir disoproxil fumarate; 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs). Other Name: TDF/FTC; Drug: Ritonavir; 100 mg taken orally once daily. A protease inhibitor (PI). Other Name: RTV; Drug: Darunavir; 100 mg taken orally once daily. A protease inhibitor (PI). Other Name: RTV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Rate of Change in Right Common Carotid Artery Intima-media Thickness (CIMT)	Right common carotid artery intima-media thickness was measured by ultrasound scan at study entry and weeks 48, 96 and 144. The annual rate of change in right common carotid artery intima-media thickness (CIMT) was estimated over 144 weeks from study entry using mixed effects linear regression model that adjusted for screening HIV-1 RNA level and Framingham risk score stratification factors.	Study entry, week 144
Change in Brachial Artery (BA) Flow Mediated Dilation (FMD) From Study Entry to Week 24	Brachial artery flow mediated dilation was measured by brachial artery reactivity tests. All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments. The change from study entry to week 24 in brachial artery FMD (%) was defined as the maximum FMD (%) calculated from resting heart rate (RH) 60 seconds and RH 90 seconds, relative to resting brachial artery diameter.	Study entry, week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brachial Artery Flow Mediated Dilation (FMD) From Study Entry to Weeks 4 and 48	Brachial artery flow mediated dilation was measured by brachial artery reactivity tests. All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments. The change from study entry to weeks 4 and 48 in brachial artery FMD (%) was defined as the maximum FMD (%) calculated from resting heart rate (RH) 60 seconds and RH 90 seconds, relative to resting brachial artery diameter.	Study entry, weeks 4 and 48
Change in Absolute Flow Mediated Dilation (FMD) From Study Entry to Weeks 4, 24 and 48	The change in absolute FMD was defined as the maximum absolute FMD from the RH 60 and 90 second measurements, from study entry to weeks 4, 24, and 48 (unit of measure millimeters). All results reflect measures captured from participants who reported fasting and not smoking for at least 8 hours prior to FMD assessments.	Study entry, weeks 4, 24 and 48
Percent Change in Bone Mineral Density (BMD) of the Hip From Study Entry to Week 96	Bone mineral density (BMD) of the hip was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and study week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Bone Mineral Density (BMD) of the Lumber Spine From Study Entry to Week 96	Bone mineral density (BMD) of the lumber spine was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and study week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Bone Mineral Density (BMD) of the Total Body From Study Entry to Week 96	Bone mineral density (BMD) of the total body was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and study week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Total Limb Fat From Study Entry to Week 96	Total limb fat was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Trunk Fat From Study Entry to Week 96	Trunk fat was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Lean Mass From Study Entry to Week 96	Lean mass was evaluated by dual-energy x-ray absorptiometry (DXA) scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Visceral Abdominal Fat (VAT) From Study Entry to Week 96	Visceral abdominal fat (VAT) was evaluated by single slice abdominal computerized tomography scans at study entry and week 96. The percent change was calculated as as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
Percent Change in Subcutaneous Abdominal Fat (SAT) From Study Entry to Week 96	Subcutaneous abdominal fat (SAT) was evaluated by single slice abdominal computerized tomography scans at study entry and week 96. The percent change was calculated as ((week 96 value - study entry value) / study entry value)) x 100.	Study entry, week 96
CD4+ T-cell Count at Study Entry and Weeks 24, 48, 96 and 144	The absolute levels of CD4+ T-cell counts (cells/mm^3) measured at study entry and weeks 24, 48, 96 and 144.	Study entry, weeks 24, 48, 96 and 144
Change in CD4+ T-cell Count From Study Entry to Weeks 24, 48, 96 and 144	Change was calculated as (CD4+ T-cell count at week 24, 48, 96, or 144) - (CD4+ T-cell count at study entry).	Study entry to weeks 24, 48, 96, and 144
Change in Fasting Total Cholesterol (TC) From Study Entry to Weeks 4, 24, 48 and 96	Total cholesterol (TC, unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in TC was calculated as (week 4, 24, 48 or 96 result) - (study entry result).	Study entry, weeks 4, 24, 48 and 96
Change in Fasting Triglyceride (TG) From Study Entry to Weeks 4, 24, 48 and 96	Triglyceride (TG, unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in TG was calculated as (week 4, 24, 48 or 96 result) - (study entry result).	Study entry, weeks 4, 24, 48 and 96
Change in Fasting High-density Lipoprotein Cholesterol (HDL-C) From Study Entry to Weeks 4, 24, 48 and 96	HDL cholesterol (unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in HDL-C was calculated as (week 4, 24, 48 or 96 result) - (study entry result).	Study entry, weeks 4, 24, 48 and 96
Change in Fasting Calculated Low-density Lipoprotein Cholesterol (LDL-C) From Study Entry to Weeks 4, 24, 48 and 96	Calculated LDL-C (unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96 from participants who reported fasting for at least 8 hours prior to assessment; all results were centrally laboratory tested in batch. Change in calculated LDL-C was calculated as (week 4, 24, 48 or 96 result) - (study entry result).	Study entry, weeks 4, 24, 48 and 96
Change in Fasting Glucose Level From Study Entry to Weeks 4, 24, 48 and 96	Glucose (unit of measure mg/dL) was measured at study entry and weeks 4, 24, 48 and 96; all results reflect measures captured from participants who reported fasting for at least 8 hours prior to assessment. Change was calculated as (fasting result during at week 4, 24, 48 or 96) - (fasting result at study entry).	Study entry, weeks 4, 24, 48 and 96
Change in Fasting Insulin Level From Study Entry to Weeks 4, 24, 48 and 96	Insulin (unit of measure uIU/dL) was measured at study entry and weeks 4, 24, 48 and 96; all results reflect measures captured from participants who reported fasting for at least 8 hours prior to assessment. Change was calculated as (fasting result during at week 4, 24, 48 or 96) - (fasting result at study entry).	Study entry, weeks 4, 24, 48 and 96
Fold Change in D-dimer From Study Entry to Weeks 48 and 96	D-dimer was measured at study entry and weeks 48 and 96 (unit of measure ug/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.	Study entry, weeks 48 and 96
Fold Change in High Sensitivity C-reactive Protein (hsCRP) From Study Entry to Weeks 48 and 96	hsCRP was measured at study entry and weeks 48 and 96 (unit of measure ug/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.	Study entry, weeks 48 and 96
Fold Change in Interleukin-6 (IL-6) From Study Entry to Weeks 48 and 96	IL-6 was measured at study entry and weeks 48 and 96 (unit of measure pg/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.	Study entry, weeks 48 and 96
Fold Change in Soluble CD14 From Study Entry to Weeks 48 and 96	Soluble CD14 was measured at study entry and weeks 48 and 96 (unit of measure ng/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.	Study entry, weeks 48 and 96
Fold Change in Soluble CD163 From Study Entry to Weeks 48 and 96	Soluble CD163 was measured at study entry and weeks 48 and 96 (unit of measure ng/ml). Fold change from study entry to week 48 or week 96 was calculated as (week 48 value or week 96 value) / (study entry value). Results identified above or below the limit of quantification were imputed at the quantification limit of the respective assay.	Study entry, weeks 48 and 96
Fold Change in Percent Expression of CD38+HLADR+ on CD4+ (Percent) From Study Entry to Weeks 24 and 96	Percent expression of CD38+HLADR+ on CD4+ was measured at study entry and weeks 24 and 96 (unit of measure percent). Fold change from study entry to week 24 or week 96 was calculated as (week 24 value or week 96 value) / (study entry value).	Study entry, weeks 24 and 96
Fold Change in Percent Expression of CD38+HLADR+ on CD8+ (Percent) From Study Entry to Weeks 24 and 96	Percent expression of CD38+HLADR+ on CD8+ was measured at study entry and weeks 24 and 96 (unit of measure percent). Fold change from study entry to week 24 or week 96 was calculated as (week 24 value or week 96 value) / (study entry value).	Study entry, weeks 24 and 96

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Todd Brown, MD, PhD, Johns Hopkins University; Study Chair: James Stein, MD, University of Wisconsin, Madison; Study Chair: Grace McComsey, MD, FIDSA, University Hospitals Cleveland Medical Center; Study Chair: Judith Currier, MD, MSc, UCLA AIDS Prevention & Treatment CTU

Publications and helpful links

General Publications

• Lennox JL, Landovitz RJ, Ribaudo HJ, Ofotokun I, Na LH, Godfrey C, Kuritzkes DR, Sagar M, Brown TT, Cohn SE, McComsey GA, Aweeka F, Fichtenbaum CJ, Presti RM, Koletar SL, Haas DW, Patterson KB, Benson CA, Baugh BP, Leavitt RY, Rooney JF, Seekins D, Currier JS; ACTG A5257 Team. Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014 Oct 7;161(7):461-71. doi: 10.7326/M14-1084. Erratum In: Ann Intern Med. 2014 Nov 4;161(9):680.
• Ofotokun I, Na LH, Landovitz RJ, Ribaudo HJ, McComsey GA, Godfrey C, Aweeka F, Cohn SE, Sagar M, Kuritzkes DR, Brown TT, Patterson KB, Para MF, Leavitt RY, Villasis-Keever A, Baugh BP, Lennox JL, Currier JS; AIDS Clinical Trials Group (ACTG) A5257 Team. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis. 2015 Jun 15;60(12):1842-51. doi: 10.1093/cid/civ193. Epub 2015 Mar 12.
• Vardhanabhuti S, Ribaudo HJ, Landovitz RJ, Ofotokun I, Lennox JL, Currier JS, Olson LM, Haas DW. Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia. Open Forum Infect Dis. 2015 Jul 1;2(3):ofv085. doi: 10.1093/ofid/ofv085. eCollection 2015 Sep.
• Stein JH, Ribaudo HJ, Hodis HN, Brown TT, Tran TT, Yan M, Brodell EL, Kelesidis T, McComsey GA, Dube MP, Murphy RL, Currier JS. A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. AIDS. 2015 Sep 10;29(14):1775-83. doi: 10.1097/QAD.0000000000000762. Erratum In: AIDS. 2016 Jan;30(2):337.
• Kelesidis T, Tran TT, Stein JH, Brown TT, Moser C, Ribaudo HJ, Dube MP, Murphy R, Yang OO, Currier JS, McComsey GA. Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s. Clin Infect Dis. 2015 Aug 15;61(4):651-60. doi: 10.1093/cid/civ327. Epub 2015 Apr 22. Erratum In: Clin Infect Dis. 2020 Dec 31;71(11):3020-3022.
• Brown TT, Moser C, Currier JS, Ribaudo HJ, Rothenberg J, Kelesidis T, Yang O, Dube MP, Murphy RL, Stein JH, McComsey GA. Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir. J Infect Dis. 2015 Oct 15;212(8):1241-9. doi: 10.1093/infdis/jiv194. Epub 2015 May 5. Erratum In: J Infect Dis. 2020 Jun 11;221(12):2083-2084.
• Stein JH, Brown TT, Ribaudo HJ, Chen Y, Yan M, Lauer-Brodell E, McComsey GA, Dube MP, Murphy RL, Hodis HN, Currier JS. Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naive individuals with HIV infection. AIDS. 2013 Mar 27;27(6):929-937. doi: 10.1097/QAD.0b013e32835ce27e.
• Brown TT, Chen Y, Currier JS, Ribaudo HJ, Rothenberg J, Dube MP, Murphy R, Stein JH, McComsey GA. Body composition, soluble markers of inflammation, and bone mineral density in antiretroviral therapy-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):323-30. doi: 10.1097/QAI.0b013e318295eb1d.
• Hughey CM, Vuong BW, Ribaudo HB, Mitchell CCK, Korcarz CE, Hodis HN, Currier JS, Stein JH. Grayscale Ultrasound Texture Features of Carotid and Brachial Arteries in People With HIV Infection Before and After Antiretroviral Therapy. J Am Heart Assoc. 2022 Mar;11(5):e024142. doi: 10.1161/JAHA.121.024142. Epub 2022 Feb 18.
• Debroy P, Lake JE, Moser C, Olefsky M, Erlandson KM, Scherzinger A, Stein JH, Currier JS, Brown TT, McComsey GA. Antiretroviral Therapy Initiation Is Associated With Decreased Visceral and Subcutaneous Adipose Tissue Density in People Living With Human Immunodeficiency Virus. Clin Infect Dis. 2021 Mar 15;72(6):979-986. doi: 10.1093/cid/ciaa196.
• McComsey GA, Moser C, Currier J, Ribaudo HJ, Paczuski P, Dube MP, Kelesidis T, Rothenberg J, Stein JH, Brown TT. Body Composition Changes After Initiation of Raltegravir or Protease Inhibitors: ACTG A5260s. Clin Infect Dis. 2016 Apr 1;62(7):853-62. doi: 10.1093/cid/ciw017. Epub 2016 Jan 20. Erratum In: Clin Infect Dis. 2021 Jul 1;73(1):174.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: February 24, 2009
• First Submitted That Met QC Criteria: February 24, 2009
• First Posted (Estimate): February 26, 2009

Study Record Updates

• Last Update Posted (Estimate): January 13, 2016
• Last Update Submitted That Met QC Criteria: December 9, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Antiretroviral therapy; ART; Treatment naive; Highly active antiretroviral therapy (HAART)
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Darunavir; Atazanavir Sulfate
• Other Study ID Numbers: ACTG A5260s; 1U01AI068636 (U.S. NIH Grant/Contract); ACTG A5257 metabolic substudy