Comparative Study of Three NNRTI-Sparing HAART Regimens

• ClinicalTrials.gov Identifier: NCT00811954
• Recruitment Status: Completed
• First Posted: December 19, 2008
• Results First Posted: September 5, 2014
• Last Update Posted: September 5, 2014
• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Bristol-Myers Squibb; Gilead Sciences; Merck Sharp & Dohme LLC; Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Information provided by (Responsible Party): AIDS Clinical Trials Group

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Raltegravir; Drug: Darunavir; Drug: Ritonavir; Drug: Atazanavir	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1814 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The ARDENT Study: Atazanavir, Raltegravir, or Darunavir With Emtricitabine/Tenofovir for Naive Treatment
• Study Start Date: May 2009
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

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 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
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 Name: TDF/FTC; Drug: Raltegravir; 400 mg taken orally twice daily. An integrase inhibitor (INI).; Other Name: 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 Name: TDF/FTC; Drug: Darunavir; 800 mg taken orally once daily. A protease inhibitor (PI).; Other Name: DRV; Drug: Ritonavir; 100 mg taken orally once daily. A protease inhibitor (PI).; Other Name: RTV

Outcome Measures

Primary Outcome Measures :

1. Cumulative Probability of First Virologic Failure by Week 96 [ Time Frame: From study entry to 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.

2. Cumulative Incidence of Discontinuation of the RAL or PI Component of Randomized Treatment for Toxicity by Week 96 [ Time Frame: From study entry to 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.

Secondary Outcome Measures :

1. Cumulative Incidence of First Adverse Event by Week 96 [ Time Frame: From study entry to 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.

2. Cumulative Probability of Time to Loss of Virologic Response (TLOVR) by Week 96 [ Time Frame: From study entry to 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.

3. Presence of Mutations Associated With NRTI Resistance [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ]
   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.
4. Presence of Mutations Associated With ATV/RTV or DRV/RTV Resistance [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ]
   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.
5. Presence of Mutations Associated With INI Resistance [ Time Frame: At the virologic failure at any time throughout the study (up to 213 weeks) ]
   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.
6. CD4+ T-cell Count [ Time Frame: At Weeks 24, 48, 96, and 144 ]
   The absolute levels of CD4+ T-cell counts (cells/mm3)
7. CD4+ T-cell Count Changes From Baseline [ Time Frame: Study entry to weeks 24, 48, 96, and 144 ]
   Change was calculated as the CD4+ T-cell count at week (24, 48, 96, and 144) minus the baseline CD4+ T-cell count
8. Incidence of Death or AIDS Defining Events (CDC Category C) [ Time Frame: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable ]
   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.
9. Incidence of Targeted Serious Non-AIDS Defining Events (Renal Failure, Liver Disease, Serious Metabolic Disorder, and CVD) [ Time Frame: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable ]
   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.
10. Change in Fasting Total Cholesterol Level From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]
    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.
11. Change in Fasting HDL Cholesterol Level From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]
    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.
12. Change in Fasting Triglycerides Level From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]
    Only fasting results are included. Change was calculated as the fasting triglycerides at week (48, 96, and 144) minus the baseline fasting triglycerides.
13. Change in Fasting Plasma Glucose Level From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]
    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.
14. Change in Framingham 10-year Risk of MI or Coronary Death From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]

    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.

15. Change in Waist Circumference From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]
    Change was calculated as the waist circumference (based on mid-waist circumference) at week (48, 96, and 144) minus the baseline waist circumference.
16. Change in Waist:Height Ratio From Baseline [ Time Frame: Study entry to weeks 48, 96, and 144 ]
    Change was calculated as the waist:height ratio at week (48, 96, and 144) minus the baseline waist:height ratio.
17. Self-reported Adherence [ Time Frame: At Weeks 4, 24, 48, 96, and 144 ]
    Self-reported percentage of anti-HIV medications participant had taken during the last month at weeks 4, 24, 48, 96, and 144.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Alabama Therapeutics CRS

Birmingham, Alabama, United States, 35294-2050

United States, California

Miller Children's Hospital

Long Beach, California, United States, 90806

USC CRS

Los Angeles, California, United States, 90033

UCLA CARE Center CRS

Los Angeles, California, United States, 90035

Stanford CRS

Palo Alto, California, United States, 94304

Ucsd, Avrc Crs

San Diego, California, United States, 92103

Ucsf Aids Crs

San Francisco, California, United States, 94110

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States, 90502

United States, Colorado

University of Colorado Hospital CRS

Aurora, Colorado, United States, 80045

Denver Public Health CRS

Denver, Colorado, United States, 80204

United States, District of Columbia

Georgetown University CRS (GU CRS)

Washington, District of Columbia, United States, 20007

Howard Univ. Washington DC NICHD CRS

Washington, District of Columbia, United States, 20060

United States, Florida

South Florida Childrens Diagnostic & Treatment Cen (5055)

Ft. Lauderdale, Florida, United States, 33316

University of Florida Jacksonville (5051)

Jacksonville, Florida, United States, 32209

Univ. of Miami AIDS CRS

Miami, Florida, United States, 33136

United States, Georgia

The Ponce de Leon Center CRS

Atlanta, Georgia, United States, 30308

United States, Illinois

Northwestern University CRS

Chicago, Illinois, United States, 60611

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States, 60612

United States, Louisiana

Tulane University New Orleans NICHD CRS (5095)

New Orleans, Louisiana, United States, 70112

United States, Maryland

IHV Baltimore Treatment CRS

Baltimore, Maryland, United States, 21201

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital CRS

Boston, Massachusetts, United States, 02114

Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, United States, 02115

Bmc Actg Crs

Boston, Massachusetts, United States, 02118

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States, 02215

United States, Michigan

Wayne State Univ. CRS

Detroit, Michigan, United States, 48201

Henry Ford Hosp. CRS

Detroit, Michigan, United States, 48202

United States, Missouri

Washington U CRS

St. Louis, Missouri, United States, 63110

United States, New Jersey

Cooper Univ. Hosp. CRS

Camden, New Jersey, United States, 08103

New Jersey Medical School- Adult Clinical Research Ctr. CRS

Newark, New Jersey, United States, 07103

United States, New York

Bronx-Lebanon Hosp. Ctr. CRS

Bronx, New York, United States, 10457

Cornell CRS

New York, New York, United States, 10011

NY Univ. HIV/AIDS CRS

New York, New York, United States, 10016

Metropolitan Hospital

New York, New York, United States, 10029

HIV Prevention & Treatment CRS

New York, New York, United States, 10032

AIDS Care CRS

Rochester, New York, United States, 14607

Univ. of Rochester ACTG CRS

Rochester, New York, United States, 14642

SUNY Stony Brook NICHD CRS (5040)

Stony Brook, New York, United States, 11794

United States, North Carolina

Unc Aids Crs

Chapel Hill, North Carolina, United States, 27514

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States, 27710

Regional Center for Infectious Disease, Wendover Medical Center CRS (3203)

Greensboro, North Carolina, United States, 27401

United States, Ohio

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States, 45267

Case CRS

Cleveland, Ohio, United States, 44106

Metro Health CRS

Cleveland, Ohio, United States, 44109

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States, 43210

United States, Oregon

The Research & Education Group- Portland CRS (31474)

Portland, Oregon, United States, 97209

United States, Pennsylvania

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States, 19104

Pitt CRS

Pittsburgh, Pennsylvania, United States, 15213

United States, Rhode Island

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States, 02906

United States, Tennessee

St. Jude/UTHSC CRS

Memphis, Tennessee, United States, 38105-2794

Vanderbilt Therapeutics CRS

Nashville, Tennessee, United States, 37203

United States, Texas

Trinity Health and Wellness Center

Dallas, Texas, United States, 75208

Houston AIDS Research Team CRS

Houston, Texas, United States, 77030

United States, Virginia

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, United States, 23219

United States, Washington

University of Washington AIDS CRS

Seattle, Washington, United States, 98104

Puerto Rico

San Juan City Hosp. PR NICHD CRS

Rio Piedras, Puerto Rico, 00927

Puerto Rico-AIDS CRS

San Juan, Puerto Rico, 00935

Sponsors and Collaborators

AIDS Clinical Trials Group

National Institute of Allergy and Infectious Diseases (NIAID)

Bristol-Myers Squibb

Gilead Sciences

Merck Sharp & Dohme LLC

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

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00811954
• Other Study ID Numbers: ACTG A5257; 1U01AI068636 ( U.S. NIH Grant/Contract )
• First Posted: December 19, 2008
• Results First Posted: September 5, 2014
• Last Update Posted: September 5, 2014
• Last Verified: September 2014

Keywords provided by AIDS Clinical Trials Group:

Treatment naive; Treatment inexperienced

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Ritonavir; Atazanavir Sulfate; Darunavir; Tenofovir; Emtricitabine; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors