AzTrials
AzTrials

HIV InfectionPhase 3NCT00811954

Comparative Study of Three NNRTI-Sparing HAART Regimens

A Phase 3 study testing Emtricitabine/tenofovir disoproxil fumarate, Raltegravir and Darunavir in people with HIV Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 57 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Infection
What is being tested?
Emtricitabine/tenofovir disoproxil fumarate, Raltegravir and Darunavir
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,814 participants
Where
57 sitesin 2 countries
Study dates
May 2009to Jun 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

57 sites in 2 countries.

57 sites in 2 countries

United States55 sites

  • The Ponce de Leon Center CRS

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80045

  • IHV Baltimore Treatment CRS

    Baltimore, Maryland, 21201

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294-2050

  • Massachusetts General Hospital CRS

    Boston, Massachusetts, 02114

  • Brigham and Women's Hosp. ACTG CRS

    Boston, Massachusetts, 02115

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • Cooper Univ. Hosp. CRS

    Camden, New Jersey, 08103

  • Unc Aids Crs

    Chapel Hill, North Carolina, 27514

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 45267

  • Case CRS

    Cleveland, Ohio, 44106

  • Metro Health CRS

    Cleveland, Ohio, 44109

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio, 43210

  • Trinity Health and Wellness Center

    Dallas, Texas, 75208

  • Denver Public Health CRS

    Denver, Colorado, 80204

  • Wayne State Univ. CRS

    Detroit, Michigan, 48201

  • Henry Ford Hosp. CRS

    Detroit, Michigan, 48202

  • Duke Univ. Med. Ctr. Adult CRS

    Durham, North Carolina, 27710

  • South Florida Childrens Diagnostic & Treatment Cen (5055)

    Fort Lauderdale, Florida, 33316

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

    Greensboro, North Carolina, 27401

  • Houston AIDS Research Team CRS

    Houston, Texas, 77030

  • University of Florida Jacksonville (5051)

    Jacksonville, Florida, 32209

  • Miller Children's Hospital

    Long Beach, California, 90806

  • USC CRS

    Los Angeles, California, 90033

  • UCLA CARE Center CRS

    Los Angeles, California, 90035

  • St. Jude/UTHSC CRS

    Memphis, Tennessee, 38105-2794

  • Univ. of Miami AIDS CRS

    Miami, Florida, 33136

  • Vanderbilt Therapeutics CRS

    Nashville, Tennessee, 37203

  • Tulane University New Orleans NICHD CRS (5095)

    New Orleans, Louisiana, 70112

  • Cornell CRS

    New York, New York, 10011

  • NY Univ. HIV/AIDS CRS

    New York, New York, 10016

  • Metropolitan Hospital

    New York, New York, 10029

  • HIV Prevention & Treatment CRS

    New York, New York, 10032

  • New Jersey Medical School- Adult Clinical Research Ctr. CRS

    Newark, New Jersey, 07103

  • Stanford CRS

    Palo Alto, California, 94304

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania, 19104

  • Pitt CRS

    Pittsburgh, Pennsylvania, 15213

  • The Research & Education Group- Portland CRS (31474)

    Portland, Oregon, 97209

  • The Miriam Hosp. ACTG CRS

    Providence, Rhode Island, 02906

  • Virginia Commonwealth Univ. Medical Ctr. CRS

    Richmond, Virginia, 23219

  • AIDS Care CRS

    Rochester, New York, 14607

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Ucsd, Avrc Crs

    San Diego, California, 92103

  • Ucsf Aids Crs

    San Francisco, California, 94110

  • University of Washington AIDS CRS

    Seattle, Washington, 98104

  • Washington U CRS

    St Louis, Missouri, 63110

  • SUNY Stony Brook NICHD CRS (5040)

    Stony Brook, New York, 11794

  • Bronx-Lebanon Hosp. Ctr. CRS

    The Bronx, New York, 10457

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

  • Georgetown University CRS (GU CRS)

    Washington D.C., District of Columbia, 20007

  • Howard Univ. Washington DC NICHD CRS

    Washington D.C., District of Columbia, 20060

Other trials in United States

Puerto Rico2 sites

  • San Juan City Hosp. PR NICHD CRS

    Rio Piedras, 00927

  • Puerto Rico-AIDS CRS

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: 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.

Read the 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.

Conditions
HIV Infection
Being tested
Emtricitabine/tenofovir disoproxil fumarate, Raltegravir, Darunavir, Ritonavir, Atazanavir
Keywords
Treatment naive, Treatment inexperienced
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Emtricitabine/tenofovir disoproxil fumarateDrug

    Also called TDF/FTC

    200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally daily. A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs).

  • RaltegravirDrug

    Also called RAL

    400 mg taken orally twice daily. An integrase inhibitor (INI).

  • DarunavirDrug

    Also called DRV

    800 mg taken orally once daily. A protease inhibitor (PI).

  • RitonavirDrug

    Also called RTV

    100 mg taken orally once daily. A protease inhibitor (PI).

  • AtazanavirDrug

    Also called ATV

    300 mg taken orally once daily. A protease inhibitor (PI).

Study groups in NCT00811954
Study groupRoleWhat they receive
Arm A: ATV/RTV + FTC/TDFExperimentalEmtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily.
Receives: Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Ritonavir; Drug: Atazanavir
Arm B: RAL + FTC/TDFExperimentalFTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily.
Receives: Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Raltegravir
Arm C: DRV/RTV + FTC/TDFExperimentalFTC/TDF, darunavir (DRV), and RTV, orally, once daily.
Receives: Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Darunavir; Drug: Ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From study entry to week 96

  2. 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.

    Measured: From study entry to week 96

Secondary outcomes (17)

  1. 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.

    Measured: From study entry to week 96

  2. 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.

    Measured: From study entry to week 96

  3. 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.

    Measured: At the virologic failure at any time throughout the study (up to 213 weeks)

  4. 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.

    Measured: At the virologic failure at any time throughout the study (up to 213 weeks)

  5. 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.

    Measured: At the virologic failure at any time throughout the study (up to 213 weeks)

  6. CD4+ T-cell Count

    The absolute levels of CD4+ T-cell counts (cells/mm3)

    Measured: At Weeks 24, 48, 96, and 144

  7. 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

    Measured: Study entry to weeks 24, 48, 96, and 144

  8. 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.

    Measured: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable

  9. 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.

    Measured: Study entry to off-study at any time throughout the study (up to 213 weeks), participant follow-up time was variable

  10. 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.

    Measured: Study entry to weeks 48, 96, and 144

  11. 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.

    Measured: Study entry to weeks 48, 96, and 144

  12. 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.

    Measured: Study entry to weeks 48, 96, and 144

  13. 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.

    Measured: Study entry to weeks 48, 96, and 144

  14. 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.

    Measured: Study entry to weeks 48, 96, and 144

  15. 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.

    Measured: Study entry to weeks 48, 96, and 144

  16. 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.

    Measured: Study entry to weeks 48, 96, and 144

  17. 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.

    Measured: At Weeks 4, 24, 48, 96, and 144

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2008 (estimated)
  2. Study startMay 2009
  3. Primary completionJun 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,814 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00811954
Sponsor's protocol ID
ACTG A5257
Other IDs
1U01AI068636
Status last verified
Sep 2014
First submitted
18 Dec 2008
Last updated
5 Sep 2014
Data monitoring committee
Yes

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.

    PubMed 17720662

  • 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.

    PubMed 18641035

  • 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.

    PubMed 17721395

  • 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.

    PubMed 18722869

  • 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.

    PubMed 35179037

  • 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.

    PubMed 33901188

  • 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.

    PubMed 33870433

  • 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.

    PubMed 26797215

  • 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.

    PubMed 25904376

  • 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.

    PubMed 25767256

  • 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.

    PubMed 25285539

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Emtricitabine/tenofovir disoproxil fumarate, Raltegravir and Darunavir in people with HIV Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 57 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Probability of First Virologic Failure by Week 96 (time frame: From study entry to week 96). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00811954, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2014.

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