Comparative Study of Three NNRTI-Sparing HAART Regimens

The ARDENT Study: Atazanavir, Raltegravir, or Darunavir With Emtricitabine/Tenofovir for Naive Treatment

The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV infected patients who have never received anti-HIV therapy be treated with a triple drug regimen. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen may not be an option for everyone, hence alternative regimens are needed.

This study was designed to look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy. This study 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

Of the five anti-HIV drug classes, four were recommended as first-line regimens for patients who have never received anti-HIV treatment before (treatment naive): nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), Integrase Inhibitors (INIs) and protease inhibitors (PIs). The U.S. Department of Health and Human Services (HHS) guidelines recommend that treatment-naive HIV infected patients be treated with a triple drug regimen that includes 2 NRTIs + 1 NNRTI, 2 NRTIs + INI, or 2 NRTIs + 1 PI as their initial treatment regimen.

According to data, an efavirenz (EFV)-containing regimen (2 NRTIs + 1 NNRTI, with EFVas the NNRTI) requires fewer pills for the patient, has mild and few side effects, and is more effective in reducing viral load than other regimens, making it the preferred choice for most patients. However, for some patients, an EFV-containing regimen is not feasible due to side effects, acquired NNRTI-resistant HIV virus, or other undesirable effects. For these patients, it is necessary to find alternative regimens with comparable safety and efficacy. This study examined how well different combinations of anti-HIV drugs work, including safety and drug tolerability for various combinations.

This was a phase III, prospective, randomized study. Participants was randomly assigned to one of three different groups (treatment arms)-A, B, or C -each representing a different drug combination regimen, none of which contained an NNRTI.

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

Arm B: Raltegravir (RAL) + FTC/TDF

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

The duration of this study was between 96 and 192 weeks, depending on when the participant enrolled. There were a total of 1,809 participants, approximately 600 per treatment arm. Screening and pre-entry evaluations must occur prior to the participant starting any study medication, treatments, or interventions. Participants were randomly assigned to their treatment groups at the entry visit and must begin treatment within 72 hours of randomization. Participants was told which group they were in and what medications they were administered. The study drugs were distributed at entry. All drugs were provided by the study with the exception of RTV, which would have to be obtained through the participant's primary care physician (Group A or C). If a participant was unable to tolerate any of the study medications during the course of the study then their doctor could switch them to another regimen.

During the study, participants was asked to return to the clinic at Weeks 4, 8, 16, 24, 36, and 48 and then every 16 weeks until the end of the study. They were also contacted by telephone during Week 2 to check on their status. Visits were last about 1 hour. At most visits, participants had a physical exam and answered questions about any medications they were taken. Additionally, participants completed questionnaires addressing their smoking and alcohol habits, had blood drawn, and were asked to give urine samples. At some visits, participants had to come to the clinic without having eaten for 8 hours. If the participant was female and able to become pregnant, a pregnancy test might be given at any visit if pregnancy was suspected.

Some participants of A5257 were asked to participate in an optional metabolic substudy A5260s. This substudy took place at only some study sites and continued last up to 144 weeks, including time on A5257. The primary focus of this substudy was to examine carotid artery intima-media thickness (CIMT) as it relates to both RTV- and RAL-containing regimens. Randomization, stratification, treatment assignments, and study visits were as per A5257.

• Study Type: Interventional
• Enrollment (Actual): 1814
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00927
    • San Juan City Hosp. PR NICHD CRS
  • San Juan, Puerto Rico, 00935
    • Puerto Rico-AIDS CRS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-2050
      • Alabama Therapeutics CRS
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital
    • Los Angeles, California, United States, 90033
      • USC CRS
    • Los Angeles, California, United States, 90035
      • UCLA CARE Center CRS
    • Palo Alto, California, United States, 94304
      • Stanford CRS
    • San Diego, California, United States, 92103
      • Ucsd, Avrc 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
    • Denver, Colorado, United States, 80204
      • Denver Public Health CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard Univ. Washington DC NICHD CRS
    • Washington, District of Columbia, United States, 20007
      • Georgetown University CRS (GU CRS)
  • Florida
    • Ft. Lauderdale, Florida, United States, 33316
      • South Florida Childrens Diagnostic & Treatment Cen (5055)
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville (5051)
    • Miami, Florida, United States, 33136
      • Univ. of Miami AIDS CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • The Ponce de Leon Center CRS
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
    • Chicago, Illinois, United States, 60612
      • Rush Univ. Med. Ctr. ACTG CRS
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University New Orleans NICHD CRS (5095)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Adult AIDS CRS
    • Baltimore, Maryland, United States, 21201
      • IHV Baltimore Treatment CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Bmc Actg Crs
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med. Ctr., ACTG CRS
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hosp. ACTG CRS
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital CRS
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hosp. CRS
    • Detroit, Michigan, United States, 48201
      • Wayne State Univ. CRS
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington U CRS
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Univ. Hosp. CRS
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School- Adult Clinical Research Ctr. CRS
  • New York
    • Bronx, New York, United States, 10457
      • Bronx-Lebanon Hosp. Ctr. CRS
    • New York, New York, United States, 10016
      • NY Univ. HIV/AIDS CRS
    • New York, New York, United States, 10011
      • Cornell CRS
    • New York, New York, United States, 10032
      • HIV Prevention & Treatment CRS
    • New York, New York, United States, 10029
      • Metropolitan Hospital
    • Rochester, New York, United States, 14642
      • Univ. of Rochester ACTG CRS
    • Rochester, New York, United States, 14607
      • AIDS Care CRS
    • Stony Brook, New York, United States, 11794
      • SUNY Stony Brook NICHD CRS (5040)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Unc Aids Crs
    • Durham, North Carolina, United States, 27710
      • Duke Univ. Med. Ctr. Adult CRS
    • Greensboro, North Carolina, United States, 27401
      • Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Univ. of Cincinnati CRS
    • Cleveland, Ohio, United States, 44106
      • Case CRS
    • Cleveland, Ohio, United States, 44109
      • Metro Health CRS
    • Columbus, Ohio, United States, 43210
      • The Ohio State Univ. AIDS CRS
  • Oregon
    • Portland, Oregon, United States, 97209
      • The Research & Education Group- Portland CRS (31474)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hosp. of the Univ. of Pennsylvania CRS
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pitt CRS
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hosp. ACTG CRS
  • Tennessee
    • Memphis, Tennessee, United States, 38105-2794
      • St. Jude/UTHSC CRS
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Therapeutics CRS
  • Texas
    • Dallas, Texas, United States, 75208
      • Trinity Health and Wellness Center
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth Univ. Medical Ctr. CRS
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington AIDS CRS

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• HIV-1 infected
• No evidence of any exclusionary mutations defined as any major NRTI or PI resistance-associated mutation on any genotype or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not excluded. More information on this criterion can be found in the study protocol.
• No prior anti-HIV therapy. More information on this criterion can be found in the study protocol.
• Viral load is 1000 copies/mL or higher, as measured within 90 days prior to study entry
• Certain laboratory values obtained within 60 days prior to study entry
• Ability to obtain RTV by prescription
• Completed cardiovascular risk assessment. More information on this criterion can be found in the study protocol.
• Must agree to use acceptable forms of contraception while receiving study drugs and for 6 weeks after stopping the medications. More information on this criterion is available in the protocol.
• Negative pregnancy test within 72 hours before initiating antiretroviral medication
• Participating in research at any AIDS Clinical Trial Group (ACTG) clinical research site or select International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group sites
• Ability and willingness of subject or legal guardian/representative to give written informed consent

Exclusion Criteria:

• Use of immunomodulators, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Those using stable physiologic glucocorticoid doses, a short course of pharmacologic glucocorticoid, corticosteroids for acute therapy treating an opportunistic infection, inhaled or topical corticosteroids, or granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) will not be excluded.
• Known allergy or sensitivity to study drugs or their ingredients. A history of sulfa allergy is not excluded.
• Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study
• Serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 7 days prior to study entry
• Requirement for any current medications that are prohibited with any study drugs
• Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness
• Any prior use of entecavir for treatment of hepatitis B for greater than 8 weeks while the participant was known to be HIV infected
• Presence of decompensated cirrhosis
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 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 Names: TDF/FTC; Drug: Ritonavir; 100 mg taken orally once daily. A protease inhibitor (PI).; Other Names: RTV; Drug: Atazanavir; 300 mg taken orally once daily. A protease inhibitor (PI).; Other Names: ATV
EXPERIMENTAL: Arm 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 Names: TDF/FTC; Drug: Raltegravir; 400 mg taken orally twice daily. An integrase inhibitor (INI).; Other Names: RAL
EXPERIMENTAL: Arm 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 Names: TDF/FTC; Drug: Ritonavir; 100 mg taken orally once daily. A protease inhibitor (PI).; Other Names: RTV; Drug: Darunavir; 800 mg taken orally once daily. A protease inhibitor (PI).; Other Names: DRV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Probability of First Virologic Failure by Week 96	The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 96. Time to virologic failure was defined as the first time from study entry to the first of two consecutive HIV-1 RNA >1000 copies/mL at or after week 16 and before week 24, or >200 copies/mL at or after week 24. Week 16 is defined to occur between 14 (98 days) and 18 weeks (126 days) after study entry, week 24 is defined to occur between 22 (154 days) and 26 (182 days) after study entry, and week 96 is defined to occur between 88 (616 days) and 104 (728 days) after study entry.	From study entry to week 96
Cumulative Incidence of Discontinuation of the RAL or PI Component of Randomized Treatment for Toxicity by Week 96	The cumulative incidence of discontinuation for toxicity by week 96 was estimated using competing risks with treatment discontinuation for other reasons considered as a competing event; participants completing the study on the RAL or PI component of their randomized regimen were considered censored at the earliest of the date of last patient contact and off study date.	From study entry to week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of First Adverse Event by Week 96	The cumulative incidence of first adverse event (with and without total bilirubin and creatine kinase and measured from study entry) by week 96 was estimated using methods for competing risks. Discontinuation of randomized treatment prior to an adverse event was considered a competing event. The time to the first of any post-entry Grade 2, 3, or 4 sign or symptom, or Grade 3 or 4 laboratory abnormality while on randomization. The protocol required reporting of signs and symptoms and laboratory values as follow: all signs and symptoms grade ≥2 post-entry to week 48, signs and symptoms grade >3 after week 48, and laboratory values grade >3 and all signs, symptoms, and laboratory values that led to a change in treatment, regardless of grade throughout out all post-entry follow-up.	From study entry to week 96
Cumulative Probability of Time to Loss of Virologic Response (TLOVR) by Week 96	The Kaplan-Meier estimate of the cumulative probability of TROVR by week 96. A composite TLOVR endpoint defined in the CDER of the FDA document "Guidance for Industry - Antiretroviral Drugs Using Plasma HIV RNA Measurements - Clinical Consideration for Accelerated and Traditional Approval" (Appendix B, pages 20) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070968.pdf. If participants never achieved a confirmed HIV-1 RNA≤200 cp/mL (on two consecutive visits) prior to death, permanent discontinuation of randomized treatment, or time of last available HIV-1 RNA evaluation, TLOVR was equal to 0; otherwise, TLOVR was the earliest time of permanent discontinuation of randomized treatment prior to study close-out period, time to confirmed levels >200 cp/mL, or time to death. If TLOVR is immediately preceded by a single missing scheduled visit or multiple consecutive missing scheduled visits, TLOVR is replaced by the first such missing visit.	From study entry to week 96
Presence of Mutations Associated With NRTI Resistance	The number of participants with NRTI resistance determined by the Stanford resistance scoring algorithm (Version 6.3). All sequencing was performed regardless of status on randomized treatment at the time of virologic failure; no sequencing was performed on subjects not meeting virologic failure.	At the virologic failure at any time throughout the study (up to 213 weeks)
Presence of Mutations Associated With ATV/RTV or DRV/RTV Resistance	The number of participants with ATV/RTV or DRV/RTV resistance determined by the Stanford resistance scoring algorithm (Version 6.3). All sequencing was performed regardless of status on randomized treatment at the time of virologic failure; no sequencing was performed on subjects not meeting virologic failure.	At the virologic failure at any time throughout the study (up to 213 weeks)
Presence of Mutations Associated With INI Resistance	The number of participants with INI resistance determined by the Stanford resistance scoring algorithm (Version 6.3). All sequencing was performed regardless of status on randomized treatment at the time of virologic failure; no sequencing was performed on subjects not meeting virologic failure.	At the virologic failure at any time throughout the study (up to 213 weeks)
CD4+ T-cell Count	The absolute levels of CD4+ T-cell counts (cells/mm3)	At Weeks 24, 48, 96, and 144
CD4+ T-cell Count Changes From Baseline	Change was calculated as the CD4+ T-cell count at week (24, 48, 96, and 144) minus the baseline CD4+ T-cell count	Study entry to weeks 24, 48, 96, and 144
Incidence of Death or AIDS Defining Events (CDC Category C)	The incidence of death or AIDS defining events (CDC category C) was estimated as number of incident events over total person years of follow-up. Multiple new events for a single subject were counted toward events totals in estimation of event incidence; generalized estimating equations were used to estimation of robust standard errors for the incidence.	Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable
Incidence of Targeted Serious Non-AIDS Defining Events (Renal Failure, Liver Disease, Serious Metabolic Disorder, and CVD)	The incidence of targeted serious non-AIDS defining events was estimated as number of incident events over total person years of follow-up. Multiple new events for a single subject were counted toward events totals in estimation of event incidence; generalized estimating equations were used to estimation of robust standard errors for the incidence.	Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable
Change in Fasting Total Cholesterol Level From Baseline	Only fasting results are included. Change was calculated as the fasting total cholesterol at week (48, 96, and 144) minus the baseline fasting total cholesterol.	Study entry to weeks 48, 96, and 144
Change in Fasting HDL Cholesterol Level From Baseline	Only fasting results are included. Change was calculated as the fasting HDL cholesterol at week (48, 96, and 144) minus the baseline fasting HDL cholesterol.	Study entry to weeks 48, 96, and 144
Change in Fasting Triglycerides Level From Baseline	Only fasting results are included. Change was calculated as the fasting triglycerides at week (48, 96, and 144) minus the baseline fasting triglycerides.	Study entry to weeks 48, 96, and 144
Change in Fasting Plasma Glucose Level From Baseline	Only fasting results are included. Change was calculated as the fasting plasma glucose at week (48, 96, and 144) minus the baseline fasting plasma glucose.	Study entry to weeks 48, 96, and 144
Change in Framingham 10-year Risk of MI or Coronary Death From Baseline	Only risk score estimated with fasting lipid results were included. Change was calculated as the Framingham 10-year risk of MI or coronary death at week (48, 96, and 144) minus the baseline Framingham 10-year risk of MI or coronary death. Framingham 10-year risk of MI or coronary death was calculated using Hear Coronary Heart Disease (10-year risk) found at https://www.framinghamheartstudy.org/risk-functions/coronary-heart-disease/hard-10-year-risk.php. Framingham 10-year risk of MI or coronary death was calculated according to age, laboratory values of total cholesterol and HDL cholesterol, smoking status, systolic blood pressure, and treatment for hypertension. The Framingham 10-year risk of MI or coronary death was calculated as: for males: <0 point (<1 percent risk) up to ≥17 points (≥30 percent risk); whereas for females: <9 points (<1 percent risk) up to ≥25 points (≥30 percent risk). Higher scores indicate high cardiovascular risk.	Study entry to weeks 48, 96, and 144
Change in Waist Circumference From Baseline	Change was calculated as the waist circumference (based on mid-waist circumference) at week (48, 96, and 144) minus the baseline waist circumference.	Study entry to weeks 48, 96, and 144
Change in Waist:Height Ratio From Baseline	Change was calculated as the waist:height ratio at week (48, 96, and 144) minus the baseline waist:height ratio.	Study entry to weeks 48, 96, and 144
Self-reported Adherence	Self-reported percentage of anti-HIV medications participant had taken during the last month at weeks 4, 24, 48, 96, and 144.	At Weeks 4, 24, 48, 96, and 144

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: Bristol-Myers Squibb; National Institute of Allergy and Infectious Diseases (NIAID); Merck Sharp & Dohme LLC; Gilead Sciences; Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Investigators: Study Chair: Jeffrey L. Lennox, MD, Emory HIV/AIDS CTU; Study Chair: Judith Silverstein Currier, MD, MSc, UCLA AIDS Prevention & Treatment CTU; Study Chair: Raphael Landovitz, MD, MSc, UCLA AIDS Prevention & Treatment CTU; Study Chair: Igho Ofotokun, MD, Emory HIV/AIDS CTU

Publications and helpful links

General Publications

• Bartlett JA, Chen SS, Quinn JB. Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview. HIV Clin Trials. 2007 Jul-Aug;8(4):221-6. doi: 10.1310/hct0804-221.
• Duvivier C, Ghosn J, Assoumou L, Soulie C, Peytavin G, Calvez V, Genin MA, Molina JM, Bouchaud O, Katlama C, Costagliola D; ANRS 121 study group. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. J Antimicrob Chemother. 2008 Oct;62(4):797-808. doi: 10.1093/jac/dkn278. Epub 2008 Jul 18.
• Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Gilde LR, Wan H, Miller MD, Wenning LA, Teppler H; Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):125-33. doi: 10.1097/QAI.0b013e318157131c.
• Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55. doi: 10.1016/S0140-6736(08)61081-8.
• 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.
• Li B, Veturi Y, Verma A, Bradford Y, Daar ES, Gulick RM, Riddler SA, Robbins GK, Lennox JL, Haas DW, Ritchie MD. Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults. PLoS Genet. 2021 Apr 26;17(4):e1009464. doi: 10.1371/journal.pgen.1009464. eCollection 2021 Apr.
• Bares SH, Smeaton LM, Scott SE, Smith BA, Godfrey C, McComsey GA. The Association Between Weight Gain, Sex, and Immune Activation Following the Initiation of Antiretroviral Therapy. J Infect Dis. 2021 Nov 22;224(10):1765-1774. doi: 10.1093/infdis/jiab210.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (ESTIMATE): December 19, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): September 5, 2014
• Last Update Submitted That Met QC Criteria: September 4, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Treatment naive; Treatment inexperienced
• 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 A5257; 1U01AI068636 (U.S. NIH Grant/Contract)