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Ensayos clínicos

Ensayos clínicos

Comparative Study of Three NNRTI-Sparing HAART Regimens

Patrocinador(es) del estudio: AIDS Clinical Trials Group
Números de identificación: NCT00811954, ACTG A5257
  • En curso, con inscripciones cerradas

Propósito del estudio

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 has been shown to cause undesirable side effects for some patients and is therefore not an option. Alternative regimens are needed for these patients. This study will 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 will also examine drug tolerability and safety for the various drug combinations.

Afección:Fase:
Infecciones por el VIH
Fase 3

Detalles del estudio

Of the five anti-HIV drug classes, three are 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),

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 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 possible due to

dangerous 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 will examine how well different combinations of anti-HIV drugs work,

including safety and drug tolerability for various combinations.



This is a phase III, prospective, randomized study. Participants will be randomly assigned

to one of three different groups (treatment arms)—A, B, or C —each representing a different

drug combination regimen, none of which will contain 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 will be between 96 and 192 weeks, depending on when the

participant enrolls. There will be a total of 1,800 participants, 600 per treatment arm.

Screening and pre-entry evaluations must occur prior to the participant starting any study

medication, treatments, or interventions. Participants will be randomly assigned to their

treatment groups at the entry visit and must begin treatment within 72 hours of

randomization. Participants will be told which group they are in and what medications they

will be administered. The study drugs will be distributed at entry. All drugs are provided

by the study with the exception of RTV, which will have to be obtained through the

participant's primary care physician (Group A or C). If a participant is unable to tolerate

any of the study medications during the course of the study then their doctor can switch

them to another regimen.



During the study, participants will be 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 will also be contacted

by telephone during Week 2 to check on their status. Visits will last about 1 hour. At most

visits, participants will have a physical exam and will answer questions about any

medications they may be taking. Additionally, participants will complete questionnaires

addressing their smoking and alcohol habits, will have blood drawn, and will be asked to

give urine samples. At some visits, participants will have to come to the clinic without

having eaten for 8 hours. If the participant is female and able to become pregnant, a

pregnancy test may be given at any visit if pregnancy is suspected.



In the first 10 participant at each imaging site, the flow-mediated vasodilation (FMD) test,

which measures cardiovascular risk, will be completed twice. This test will be performed on

Week 24.



Some participants of A5257 will be asked to participate in an optional metabolic substudy of

A5257. This substudy will take place at only some study sites and may last up to 144 weeks,

including time on A5257. The primary focus of this substudy is 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 will be as per A5257.Of the five anti-HIV drug classes, three are 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),

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 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 possible due to

dangerous 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 will examine how well different combinations of anti-HIV drugs work,

including safety and drug tolerability for various combinations.



This is a phase III, prospective, randomized study. Participants will be randomly assigned

to one of three different groups (treatment arms)—A, B, or C —each representing a different

drug combination regimen, none of which will contain 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 will be between 96 and 192 weeks, depending on when the

participant enrolls. There will be a total of 1,800 participants, 600 per treatment arm.

Screening and pre-entry evaluations must occur prior to the participant starting any study

medication, treatments, or interventions. Participants will be randomly assigned to their

treatment groups at the entry visit and must begin treatment within 72 hours of

randomization. Participants will be told which group they are in and what medications they

will be administered. The study drugs will be distributed at entry. All drugs are provided

by the study with the exception of RTV, which will have to be obtained through the

participant's primary care physician (Group A or C). If a participant is unable to tolerate

any of the study medications during the course of the study then their doctor can switch

them to another regimen.



During the study, participants will be 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 will also be contacted

by telephone during Week 2 to check on their status. Visits will last about 1 hour. At most

visits, participants will have a physical exam and will answer questions about any

medications they may be taking. Additionally, participants will complete questionnaires

addressing their smoking and alcohol habits, will have blood drawn, and will be asked to

give urine samples. At some visits, participants will have to come to the clinic without

having eaten for 8 hours. If the participant is female and able to become pregnant, a

pregnancy test may be given at any visit if pregnancy is suspected.



In the first 10 participant at each imaging site, the flow-mediated vasodilation (FMD) test,

which measures cardiovascular risk, will be completed twice. This test will be performed on

Week 24.



Some participants of A5257 will be asked to participate in an optional metabolic substudy of

A5257. This substudy will take place at only some study sites and may last up to 144 weeks,

including time on A5257. The primary focus of this substudy is 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 will be as per A5257.

Criterios de inclusión

    :
    • HIV 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

Criterios de exclusión

    :
    • 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 Child Pugh Class C hepatic impairment
    • Presence of decompensated cirrhosis
    • Pregnant or breastfeeding

Centros de estudio/contactos

Alabama

    Alabama Therapeutics CRS, Birmingham, Alabama, 35294-2050, United States

California

    Miller Children's Hospital, Long Beach, California, 90806, United States

    USC CRS, Los Angeles, California, 90033, United States

    UCLA CARE Center CRS, Los Angeles, California, 90035, United States

    Stanford CRS, Palo Alto, California, 94304, United States

    Ucsd, Avrc Crs, San Diego, California, 92103, United States

    Ucsf Aids Crs, San Francisco, California, 94110, United States

    Harbor-UCLA Med. Ctr. CRS, Torrance, California, 90502, United States

Colorado

    University of Colorado Hospital CRS, Aurora, Colorado, 80045, United States

    Denver Public Health CRS, Denver, Colorado, 80204, United States

District of Columbia

    Georgetown University CRS (GU CRS), Washington, District of Columbia, 20007, United States

    Howard Univ. Washington DC NICHD CRS, Washington, District of Columbia, 20060, United States

Florida

    South Florida Childrens Diagnostic & Treatment Cen (5055), Ft. Lauderdale, Florida, 33316, United States

    University of Florida Jacksonville (5051), Jacksonville, Florida, 32209, United States

    Univ. of Miami AIDS CRS, Miami, Florida, 33136, United States

Georgia

    The Ponce de Leon Center CRS, Atlanta, Georgia, 30308, United States

Illinois

    Northwestern University CRS, Chicago, Illinois, 60611, United States

    Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois, 60612, United States

Louisiana

    Tulane University New Orleans NICHD CRS (5095), New Orleans, Louisiana, 70112, United States

Maryland

    Johns Hopkins Adult AIDS CRS, Baltimore, Maryland, 21287, United States

    IHV Baltimore Treatment CRS, Baltimore, Maryland, 21201, United States

Massachusetts

    Bmc Actg Crs, Boston, Massachusetts, 02118, United States

    Brigham and Women's Hosp. ACTG CRS, Boston, Massachusetts, 02115, United States

    Massachusetts General Hospital CRS, Boston, Massachusetts, 02114, United States

    Beth Israel Deaconess Med. Ctr., ACTG CRS, Boston, Massachusetts, 02215, United States

Michigan

    Henry Ford Hosp. CRS, Detroit, Michigan, 48202, United States

    Wayne State Univ. CRS, Detroit, Michigan, 48201, United States

Missouri

    Washington U CRS, St. Louis, Missouri, 63110, United States

New Jersey

    Cooper Univ. Hosp. CRS, Camden, New Jersey, 08103, United States

    New Jersey Medical School- Adult Clinical Research Ctr. CRS, Newark, New Jersey, 07103, United States

New York

    Bronx-Lebanon Hosp. Ctr. CRS, Bronx, New York, 10457, United States

    Cornell CRS, New York, New York, 10011, United States

    NY Univ. HIV/AIDS CRS, New York, New York, 10016, United States

    HIV Prevention & Treatment CRS, New York, New York, 10032, United States

    Univ. of Rochester ACTG CRS, Rochester, New York, 14642, United States

    AIDS Care CRS, Rochester, New York, 14607, United States

    SUNY Stony Brook NICHD CRS (5040), Stony Brook, New York, 11794, United States

North Carolina

    Unc Aids Crs, Chapel Hill, North Carolina, 27514, United States

    Duke Univ. Med. Ctr. Adult CRS, Durham, North Carolina, 27710, United States

    Regional Center for Infectious Disease, Wendover Medical Center CRS (3203), Greensboro, North Carolina, 27401, United States

Ohio

    Univ. of Cincinnati CRS, Cincinnati, Ohio, 45267, United States

    Case CRS, Cleveland, Ohio, 44106, United States

    Metro Health CRS, Cleveland, Ohio, 44109, United States

    The Ohio State Univ. AIDS CRS, Columbus, Ohio, 43210, United States

Oregon

    The Research & Education Group- Portland CRS (31474), Portland, Oregon, 97209, United States

Pennsylvania

    Hosp. of the Univ. of Pennsylvania CRS, Philadelphia, Pennsylvania, 19104, United States

    Pitt CRS, Pittsburgh, Pennsylvania, 15213, United States

Rhode Island

    The Miriam Hosp. ACTG CRS, Providence, Rhode Island, 02906, United States

Tennessee

    St. Jude/UTHSC CRS, Memphis, Tennessee, 38105-2794, United States

    Vanderbilt Therapeutics CRS, Nashville, Tennessee, 37203, United States

Texas

    Trinity Health and Wellness Center, Dallas, Texas, 75208, United States

    Houston AIDS Research Team CRS, Houston, Texas, 77030, United States

Virginia

    Virginia Commonwealth Univ. Medical Ctr. CRS, Richmond, Virginia, 23219, United States

Washington

    University of Washington AIDS CRS, Seattle, Washington, 98104, United States

    San Juan City Hosp. PR NICHD CRS, Rio Piedras, Washington, 00927, Puerto Rico

    Puerto Rico-AIDS CRS, San Juan, Washington, 00935, Puerto Rico

Actualizado: 30 de marzo del 2010

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