Strategic Timing of Antiretroviral Treatment

NCT ID: NCT00867048

Last Updated: 2024-03-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

4688 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-15

Study Completion Date

2022-07-27

Brief Summary

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Objectives:

* To find out if the chance of developing a serious illness or of getting AIDS is less if patients start taking HIV medicines at a time when their cluster-of-differentiation-4 (CD4)+ cell count is still fairly high, instead of waiting until the CD4+ count is at the level where there is good evidence for starting medicines.
* To learn more about how a strategy of starting HIV medicines early might affect other aspects of care, such as the chances of developing other illnesses or resistance to HIV medicines, the frequency of doctor visits, the cost of medical care, and general health and satisfaction.

Detailed Description

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Background:

* Most guidelines agree that if the number of your CD4+ cells (cells in your blood which help fight infection) drops below 350 cells/mm3, or if you have symptoms of AIDS, you should start taking HIV medicines. There are randomized trials that support this recommendation. (Randomized trials are usually considered the strongest form of evidence to support treatment decisions. Other studies, like observational studies, provide evidence too, but the evidence is often considered to be weaker than evidence from randomized trials. A randomized trial gives the most certain information about how well a treatment works because randomization makes sure each group is similar except for the treatment they receive.) Some experts believe that HIV treatment should be started even when the number of CD4+ cells is above 350 cells/mm3. For example, guidelines issued in the US in December 2009 include a new recommendation for starting HIV medicines if your CD4+ cell count is between 350 and 500 cells/mm3. However, this recommendation is based on information from observational studies, not randomized trials. We are doing this study to find out if the chances of getting a serious illness or of getting AIDS are less if people start taking HIV medicines at a time when their CD4+ cell counts are still fairly high, instead of waiting to take HIV medicines at a CD4+ count where there is good evidence for starting medicines.

Objectives:

* To find out if the chance of developing a serious illness or of getting AIDS is less if patients start taking HIV medicines at a time when their CD4+ cell count is still fairly high, instead of waiting until the CD4+ count is at the level where there is good evidence for starting medicines.
* To learn more about how a strategy of starting HIV medicines early might affect other aspects of care, such as the chances of developing other illnesses or resistance to HIV medicines, the frequency of doctor visits, the cost of medical care, and general health and satisfaction.

Eligibility:

* Patients 18 years of age and older who are infected with HIV, have CD4+ cell counts of greater than 500 cells/mm3, and who have never had antiretroviral therapy to treat HIV.

Design:

* Initial screening visits (2) to draw blood for CD4+ cell counts and provide a full medical history
* Patients will be randomly split into two groups:

Early: Patients will begin receiving HIV medications from the start of the study.

Deferred: Patients will begin to take HIV medications when the CD4 drops below 350 cells/mm3, or they develop AIDS or other symptoms of HIV infection.

* HIV medications for each patient will be determined by the study doctors.
* Evaluations during the treatment period:
* Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
* Questions about daily life, including sexual behaviors.
* Blood and urine tests.
* Heart tests with electrocardiogram.
* Patients will return for evaluations at 1 and 4 months after randomization, and every 4 months thereafter for the duration of the study.

Substudies will take advantage of the START randomization to compare outcomes in people starting ART early vs. later.

The purpose of this randomized study is to determine whether immediate initiation of antiretroviral treatment (ART) is superior to deferral of ART until the CD4+ declines below 350 cells/mm(3) in terms of morbidity and mortality in HIV-1 (subsequently referred to as HIV) infected persons who are antiretroviral naive with a CD4+ count above 500 cells/mm(3).

The study will enroll an estimated 4,000 participants. Participants will be followed for at least 3 years after enrollment, to a common closing date.

Substudies will take advantage of the START randomization to compare outcomes in people starting ART early vs. later. These will measure outcomes that do not require the entire sample size of START to determine whether early ART is related to a difference in these outcomes over the course of the study.

Conditions

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HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Early ART

Initiate ART immediately following randomization

Group Type EXPERIMENTAL

All licensed antiretroviral medications

Intervention Type DRUG

In both arms, participants may be prescribed any licensed antiretroviral medication, in accordance with national treatment guidelines. The nature of the intervention is the timing of when to begin treatment with these medications, as described in the two treatment arms.

Deferred ART

Defer ART until the CD4+ count declines to \<350 cells/cu mm or AIDS develops

Group Type ACTIVE_COMPARATOR

All licensed antiretroviral medications

Intervention Type DRUG

In both arms, participants may be prescribed any licensed antiretroviral medication, in accordance with national treatment guidelines. The nature of the intervention is the timing of when to begin treatment with these medications, as described in the two treatment arms.

Interventions

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All licensed antiretroviral medications

In both arms, participants may be prescribed any licensed antiretroviral medication, in accordance with national treatment guidelines. The nature of the intervention is the timing of when to begin treatment with these medications, as described in the two treatment arms.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Signed informed consent
* HIV infection documented by a plasma HIV RNA viral load, rapid HIV test or any licensed\* ELISA test; and confirmed by another test using a different method including but not limited to a rapid HIV test, Western Blot, HIV culture, HIV antigen, or HIV pro-viral DNA at any time prior to study entry.
* Age greater than or equal to 18 years
* Karnofsky performance score greater than or equal to 80 (an indication that the participant can perform normal activities)
* Perceived life expectancy of at least 6 months
* For women of child-bearing potential, willingness to use contraceptives as described in the product information of the ART drugs they are prescribed
* Two CD4+ cell counts greater than 500 cells/mm(3) at least 2 weeks apart within 60 days before randomization

* The term licensed refers to an FDA-approved kit or, for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country. Confirmation of the initial test result must use a test method that is different than the one used for the initial assessment.

Exclusion Criteria

* Any previous use of ART or interleukin-2 (IL-2)
* Diagnosis of any clinical AIDS event before randomization (including esophageal candidiasis and chronic Herpes simplex infection)
* Presence of HIV progression such as oral thrush, unexplained weight loss, or unexplained fever
* Cardiovascular event (myocardial infarction, angioplasty, coronary-artery bypass grafting, stroke) within 6 months before randomization
* Non-AIDS-defining cancer, excluding basal and squamous cell skin cancer, within 6 months before randomization
* Dialysis within 6 months before randomization
* Diagnosis of decompensated liver disease before randomization
* Current imprisonment, or compulsory detention (involuntary incarceration) for treatment of a psychiatric or physical illness
* Current pregnancy or breastfeeding (a negative serum or urine pregnancy test is required within 14 days before randomization for women of child-bearing potential)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark

UNKNOWN

Sponsor Role collaborator

Medical Research Council

OTHER_GOV

Sponsor Role collaborator

Kirby Institute

OTHER_GOV

Sponsor Role collaborator

Washington D.C. Veterans Affairs Medical Center

FED

Sponsor Role collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

NEAT - European AIDS Treatment Network

OTHER

Sponsor Role collaborator

National Health and Medical Research Council, Australia

OTHER

Sponsor Role collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role collaborator

Abbott

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Gilead Sciences

INDUSTRY

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Tibotec Pharmaceutical Limited

INDUSTRY

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James D Neaton, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Abdel Babiker, PhD

Role: STUDY_CHAIR

Medical Research Council Clinical Trials Unit, London

Jens Lundgren, MD, DMSc

Role: STUDY_CHAIR

Copenhagen HIV Programme

Locations

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University of Southern California

Alhambra, California, United States

Site Status

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

Site Status

UCLA CARE-4-Families (LABAC CRS)

Los Angeles, California, United States

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UCSD Mother-Child-Adolescent Program

San Diego, California, United States

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Naval Medical Center San Diego

San Diego, California, United States

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Denver Public Health

Denver, Colorado, United States

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Yale University School of Medicine

New Haven, Connecticut, United States

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Georgetown University

Washington D.C., District of Columbia, United States

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George Washington Medical Faculty Associates

Washington D.C., District of Columbia, United States

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Washington DC VA Medical Center

Washington D.C., District of Columbia, United States

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University of Florida Health Services Center

Jacksonville, Florida, United States

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University of Florida, Jacksonville

Jacksonville, Florida, United States

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University of Miami

Miami, Florida, United States

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Orlando Immunology Center

Orlando, Florida, United States

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Florida Department of Health in Orange County/Sunshine Care Center

Orlando, Florida, United States

Site Status

Infectious Diseases Associates NW FL, PA

Pensacola, Florida, United States

Site Status

Hillsborough County Health Deptment/University of South Florida

Tampa, Florida, United States

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AIDS Research and Treatment Center of the Treasure Coast

Vero Beach, Florida, United States

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Mt. Sinai Hospital

Chicago, Illinois, United States

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Lurie Children's Hospital

Chicago, Illinois, United States

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University of Illinois at Chicago

Chicago, Illinois, United States

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Tulane University Medical Center

New Orleans, Louisiana, United States

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Walter Reed National Military Medical Center

Bethesda, Maryland, United States

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

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Community Research Initiative of New England

Boston, Massachusetts, United States

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Boston Medical Center

Boston, Massachusetts, United States

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Wayne State University

Detroit, Michigan, United States

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Henry Ford Health System

Detroit, Michigan, United States

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Newland Immunology Center of Excellence (NICE)

Southfield, Michigan, United States

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Hennepin County Medical Center

Minneapolis, Minnesota, United States

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Mayo Clinic

Rochester, Minnesota, United States

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Cooper University Hospital

Camden, New Jersey, United States

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New Jersey Medical School Adult Clinical Research Center

Newark, New Jersey, United States

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Cornell CRS

New York, New York, United States

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Bronx-Lebanon Hospital Center

The Bronx, New York, United States

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Montefiore Medical Center

The Bronx, New York, United States

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UNC AIDS Clinical Trials Unit

Chapel Hill, North Carolina, United States

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Duke University

Durham, North Carolina, United States

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Regional Center for Infectious Disease

Greensboro, North Carolina, United States

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Wake County Human Services

Raleigh, North Carolina, United States

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Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

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The Ohio State University Medical Center

Columbus, Ohio, United States

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The Research + Education Group - Portland

Portland, Oregon, United States

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The Research and Education Group at Portland VA Research Foundation

Portland, Oregon, United States

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Temple University

Philadelphia, Pennsylvania, United States

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States

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UT Southwestern Clinical Research Unit

Dallas, Texas, United States

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University of North Texas Health Science Center

Fort Worth, Texas, United States

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Houston AIDS Research Team

Houston, Texas, United States

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Texas Children's Hospital

Houston, Texas, United States

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San Antonio Military Health System

San Antonio, Texas, United States

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Naval Medical Center Portsmouth

Portsmouth, Virginia, United States

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Virginia Commonwealth University

Richmond, Virginia, United States

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AIDS Resource Center of Wisconsin

Milwaukee, Wisconsin, United States

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Medical College of Wisconsin

Milwaukee, Wisconsin, United States

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Hospital Nacional Profesor Alejandro Posadas

El Palomar, Buenos Aires, Argentina

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Hospital Interzonal General de Agudos Dr. Diego Paroissien

Isidro Casanova, Buenos Aires, Argentina

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CAICI (Instituto Centralizado de Assistencia e Investigacion Clinica Integral)

Rosario, Santa Fe Province, Argentina

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FUNCEI

Buenos Aires, , Argentina

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Fundacion IDEAA

Buenos Aires, , Argentina

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Hospital General de Agudos JM Ramos Mejia

Buenos Aires, , Argentina

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Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

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Hospital Rawson

Córdoba, , Argentina

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CEIN

Neuquén, , Argentina

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Burwood Road General Practice

Burwood, New South Wales, Australia

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East Sydney Doctors

Darlinghurst, New South Wales, Australia

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Holdsworth House Medical Practice

Darlinghurst, New South Wales, Australia

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St. Vincent's Hospital

Darlinghurst, New South Wales, Australia

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Taylor Square Private Clinic

Darlinghurst, New South Wales, Australia

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Westmead Hospital

Westmead, New South Wales, Australia

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Sexual Health and HIV Service - Clinic 2

Brisbane, Queensland, Australia

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Royal Adelaide Hospital

Adelaide, South Australia, Australia

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The Alfred Hospital

Melbourne, Victoria, Australia

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Melbourne Sexual Health Centre

Melbourne, Victoria, Australia

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Prahran Market Clinic

Melbourne, Victoria, Australia

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Centre Clinic

St Kilda, Victoria, Australia

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Royal Perth Hospital

Perth, Western Australia, Australia

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Otto-Wagner-Spital SMZ /Baumgartner Hoehe

Vienna, , Austria

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University Vienna General Hospital

Vienna, , Austria

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Institute of Tropical Medicine

Antwerp, , Belgium

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Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre)

Brussels, , Belgium

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Universitaire Ziekenhuizen Gent

Ghent, , Belgium

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Universitair Ziekenhuis Gasthuisberg

Leuven, , Belgium

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Center for Infectious Diseases at the UFES

Vitória, Espírito Santo, Brazil

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SEI - Servi�os Especializados em Infectologia

Salvador, Estado de Bahia, Brazil

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Hospital Escola Sao Francisco de Assis - UFRJ

Rio de Janeiro, Rio de Janeiro, Brazil

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Ipec/Fiocruz

Rio de Janeiro, Rio de Janeiro, Brazil

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Instituto de Infectologia Emilio Ribas - IIER

São Paulo, São Paulo, Brazil

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Centro de Referencia e Treinamento DST/Aids

São Paulo, São Paulo, Brazil

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Lim 56/Hcfmusp

São Paulo, São Paulo, Brazil

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Fundacion Arriaran

Santiago, , Chile

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University Hospital Plzen, CZ

Pilsen, , Czechia

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Faculty Hospital Na Bulovce, Prague, Czech Rep.

Prague, , Czechia

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Arhus Universitetshospital, Skejby

Aarhus, , Denmark

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Rigshospitalet, Infektionsmedicinsk ambulatorium 8622

Copenhagen, , Denmark

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Hvidovre University Hospital, Department of Infectious Diseases

Hvidovre, , Denmark

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Odense University Hospital

Odense, , Denmark

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West Tallinn Central Hospital Infectious Diseases

Tallinn, , Estonia

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Helsinki University Central Hospital, Div. of Infectious Diseases CRS

Helsinki, , Finland

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CHU de Besan�on - H�pital Jean-Minjoz

Besançon, , France

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CHU C�te de Nacre

Caen, , France

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H�pital Antoine Becl�re

Clamart, , France

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H�pital Henri Mondor

Créteil, , France

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H�pital de Bicetre

Le Kremlin-Bicêtre, , France

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Groupe Hospitalier Pitie-Salpetri�re

Paris, , France

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H�pital Europeen Georges Pompidou

Paris, , France

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H�pital H�tel Dieu

Paris, , France

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H�pital Saint-Antoine

Paris, , France

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H�pital Saint-Louis

Paris, , France

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H�pital Foch

Suresnes, , France

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Centre Hospitalier - H�pital Gustave Dron

Tourcoing, , France

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EPIMED-Gesellschaft fur epidemiologische und klinische Forschung in der MedizinmbH

Berlin, , Germany

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Gemeinschaftspraxis Jessen-Jessen-Stein

Berlin, , Germany

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Medizinische Universitatsklinik - Bonn, Immunologische Ambulanz CRS

Bonn, , Germany

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Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV

Cologne, , Germany

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Klinikum Dortmund gGmbH

Dortmund, , Germany

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Universitatsklinikum Dusseldorf

Düsseldorf, , Germany

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Universitatsklinikum Erlangen

Erlangen, , Germany

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Klinik fur Dermatologie, Venerologie, Allergologie

Essen, , Germany

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Johann Wolfgang Goethe - University Hospital, Infektionsambulanz CRS

Frankfurt, , Germany

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ICH Study Center

Hamburg, , Germany

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Ifi - Studien und Projekte GmbH

Hamburg, , Germany

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Universitatsklinikum Hamburg-Eppendorf

Hamburg, , Germany

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Medizinische Hochschule Hannover

Hanover, , Germany

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Universitatsklinikum Heidelberg

Heidelberg, , Germany

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Klinikum der Universitat Munchen

Munich, , Germany

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Universitatsklinikum Regensburg

Regensburg, , Germany

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Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie CRS

Würzburg, , Germany

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Attikon University General Hospital

Athens, , Greece

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Evangelismos General Hospital

Athens, , Greece

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Hippokration University General Hospital of Athens

Athens, , Greece

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Korgialenio-Benakio Hellenic Red Cross

Athens, , Greece

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Syngros Hospital

Athens, , Greece

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AHEPA University Hospital

Thessaloniki, , Greece

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Institute of Infectious Diseases

Pune, Maharashtra, India

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YRGCARE Medical Centre VHS, Chennai CRS

Chennai, Tamil Nadu, India

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Mater Misericordiae University Hospital

Dublin, , Ireland

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Rambam Medical Center

Haifa, , Israel

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Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

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Ospedale San Raffaele S.r.l.

Milan, MI, Italy

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Lazzaro Spallanzani IRCSS

Rome, RM, Italy

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Centre Hospitalier de Luxembourg

Luxembourg, , Luxembourg

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University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, Malaysia

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Serefo/Cesac Mali

Bamako, , Mali

Site Status

INCMNSZ (Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran)

Tlalpan, , Mexico

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University Hospital Centre Ibn Rochd

Casablanca, , Morocco

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Institute of Human Virology-Nigeria (IHVN)

Abuja, Federal Capital Territory, Nigeria

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Oslo University Hospital, Ulleval

Oslo, , Norway

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Via Libre

Lima, , Peru

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Asociacion Civil IMPACTA Salud y Educacion

Lima, , Peru

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Hospital Nacional Edgardo Rebagliati Martins

Lima, , Peru

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Hospital Nacional Guillermo Almenara Irigoyen

Lima, , Peru

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Asociacion Civil Impacta Salud y Educacion - Sede San Miguel

Lima, , Peru

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Uniwersytecki Szpital Kliniczny

Bialystok, , Poland

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Wojewodzki Szpital Zakazny

Warsaw, , Poland

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EMC Instytut Medyczny SA

Wroclaw, , Poland

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Hospital Curry Cabral

Lisbon, , Portugal

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Hospital de Egas Moniz

Lisbon, , Portugal

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Hospital de Santa Maria

Lisbon, , Portugal

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Hospital Joaquim Urbano

Porto, , Portugal

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San Juan Hospital

Rio Piedras, , Puerto Rico

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University of Puerto Rico Pediatric Research Site

San Juan, , Puerto Rico

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Puerto Rico-AIDS Clinical Trials Unit (PR-ACTU)

San Juan, , Puerto Rico

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Desmond Tutu HIV Foundation Clinical Trials Unit

Cape Town, , South Africa

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Durban International Clinical Research Site (WWH)

Durban, , South Africa

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Durban International Clinical Research Site

Durban, , South Africa

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CHRU

Johannesburg, , South Africa

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1 Military Hospital

Pretoria, , South Africa

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Hospital Universitario Principe de Asturias

Alcalá de Henares, , Spain

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Hospital Universitari Germans Trias i Pujol

Badalona, , Spain

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Hospital Clinic de Barcelona

Barcelona, , Spain

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Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

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Hospital del Mar

Barcelona, , Spain

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Hospital Clinico San Carlos

Madrid, , Spain

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Hospital La Paz

Madrid, , Spain

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Hospital La Princesa, Internal Medicine and Infectious Disease Service CRS

Madrid, , Spain

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Hospital Universitario Doce de Octubre

Madrid, , Spain

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Hospital Universitari Mutua Terrassa

Terrassa, , Spain

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Hospital Universitario y Politecnico La Fe

Valencia, , Spain

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Complejo Hospitalario Xeral Cies

Vigo, , Spain

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Sahlgrenska University Hospital

Gothenburg, , Sweden

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Skane University Hospital

Malmo, , Sweden

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University Hospital Basel

Basel, , Switzerland

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Bern University Hospital

Bern, , Switzerland

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Unite VIH/SIDA Geneva

Geneva, , Switzerland

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University Hospital Zurich

Zurich, , Switzerland

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Chulalongkorn University Hospital

Bangkok, , Thailand

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Ramathibodi Hospital

Bangkok, , Thailand

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Siriraj Hospital

Bangkok Noi, , Thailand

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Sanpatong Hospital

Chiang Mai, , Thailand

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Research Institute for Health Sciences (RIHES)

Chiang Mai, , Thailand

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Chiangrai Prachanukroh Hospital

Chiang Rai, , Thailand

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Chonburi Regional Hospital

Chon Buri, , Thailand

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Khon Kaen University, Srinagarind Hospital

Khon Kaen, , Thailand

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Bamrasnaradura Institute

Nonthaburi, , Thailand

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MRC/UVRI Research Unit on AIDS

Entebbe, , Uganda

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Joint Clinical Research Center (JCRC)

Kampala, , Uganda

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Royal Berkshire Hospital

Reading, Berkshire, United Kingdom

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The James Cook University Hospital

Middlesbrough, Cleveland, United Kingdom

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Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom

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Brighton and Sussex University Hospitals NHS Trust

Brighton, East Sussex, United Kingdom

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Leicester Royal Infirmary

Leicester, Leicestershire, United Kingdom

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Belfast Health and Social Care Trust (RVH)

Belfast, Northern Ireland, United Kingdom

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Sheffield Teaching Hospital NHS Foundation Trust

Sheffield, South Yorkshire, United Kingdom

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Queen Elizabeth Hospital Birmingham

Birmingham, West Midlands, United Kingdom

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Birmingham Heartlands Hospital

Birmingham, West Midlands, United Kingdom

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Coventry and Warwickshire NHS partnership Trust

Coventry, West Midlands, United Kingdom

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Southmead Hospital

Bristol, , United Kingdom

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Gloucestershire Royal Hospital

Gloucester, , United Kingdom

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Barts Health NHS Trust

London, , United Kingdom

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Royal Free London NHS Foundation Trust

London, , United Kingdom

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Guy's and St.Thomas' NHS Foundation Trust

London, , United Kingdom

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Lewisham and Greenwich NHS Trust

London, , United Kingdom

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Chelsea and Westminster Hospital

London, , United Kingdom

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St. George's Healthcare NHS Trust

London, , United Kingdom

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Imperial College Healthcare NHS Trust

London, , United Kingdom

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University College London Medical School

London, , United Kingdom

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North Manchester General Hospital

Manchester, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Brazil Chile Czechia Denmark Estonia Finland France Germany Greece India Ireland Israel Italy Luxembourg Malaysia Mali Mexico Morocco Nigeria Norway Peru Poland Portugal Puerto Rico South Africa Spain Sweden Switzerland Thailand Uganda United Kingdom

References

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Babiker AG, Emery S, Fatkenheuer G, Gordin FM, Grund B, Lundgren JD, Neaton JD, Pett SL, Phillips A, Touloumi G, Vjechaj MJ; INSIGHT START Study Group. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study. Clin Trials. 2013;10(1 Suppl):S5-S36. doi: 10.1177/1740774512440342. Epub 2012 Apr 30.

Reference Type BACKGROUND
PMID: 22547421 (View on PubMed)

INSIGHT START Study Group; Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fatkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807. doi: 10.1056/NEJMoa1506816. Epub 2015 Jul 20.

Reference Type RESULT
PMID: 26192873 (View on PubMed)

MacDonald DM, Samorodnitsky S, Wendt CH, Baker JV, Collins G, Kruk M, Lock EF, Paredes R, Poongulali S, Weise DO, Winston A, Wood R, Kunisaki KM; INSIGHT START Pulmonary Substudy Group. Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV. Sci Rep. 2023 Mar 23;13(1):4749. doi: 10.1038/s41598-023-29739-x.

Reference Type DERIVED
PMID: 36959289 (View on PubMed)

Gabrielaite M, Bennedbaek M, Rasmussen MS, Kan V, Furrer H, Flisiak R, Losso M, Lundgren JD; INSIGHT START Study Group; Marvig RL. Deep-sequencing of viral genomes from a large and diverse cohort of treatment-naive HIV-infected persons shows associations between intrahost genetic diversity and viral load. PLoS Comput Biol. 2023 Jan 3;19(1):e1010756. doi: 10.1371/journal.pcbi.1010756. eCollection 2023 Jan.

Reference Type DERIVED
PMID: 36595537 (View on PubMed)

Gabrielaite M, Bennedbaek M, Zucco AG, Ekenberg C, Murray DD, Kan VL, Touloumi G, Vandekerckhove L, Turner D, Neaton J, Lane HC, Safo S, Arenas-Pinto A, Polizzotto MN, Gunthard HF, Lundgren JD, Marvig RL. Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity. J Infect Dis. 2021 Dec 15;224(12):2053-2063. doi: 10.1093/infdis/jiab253.

Reference Type DERIVED
PMID: 33974707 (View on PubMed)

Ghazi L, Baker JV, Sharma S, Jain MK, Palfreeman A, Necsoi C, Murray DD, Neaton JD, Drawz PE. Role of Inflammatory Biomarkers in the Prevalence and Incidence of Hypertension Among HIV-Positive Participants in the START Trial. Am J Hypertens. 2020 Jan 1;33(1):43-52. doi: 10.1093/ajh/hpz132.

Reference Type DERIVED
PMID: 31800000 (View on PubMed)

Lampe FC, Rodger AJ, Burman W, Grulich A, Friedland G, Sadr WE, Neaton J, Corbelli GM, Emery S, Molina JM, Orkin C, Gatell J, Gerstoft J, Ruxrungtham K, Barbosa de Souza M, Phillips AN; INSIGHT START Study Group. Impact of early antiretroviral treatment on sexual behaviour: a randomised comparison. AIDS. 2019 Dec 1;33(15):2337-2350. doi: 10.1097/QAD.0000000000002359.

Reference Type DERIVED
PMID: 31764099 (View on PubMed)

Wyman Engen N, Huppler Hullsiek K, Belloso WH, Finley E, Hudson F, Denning E, Carey C, Pearson M, Kagan J. A randomized evaluation of on-site monitoring nested in a multinational randomized trial. Clin Trials. 2020 Feb;17(1):3-14. doi: 10.1177/1740774519881616. Epub 2019 Oct 24.

Reference Type DERIVED
PMID: 31647325 (View on PubMed)

Castillo-Mancilla JR, Phillips AN, Neaton JD, Neuhaus J, Sharma S, Baker JV, Collins S, Mannheimer S, Pett S, Touzeau-Romer V, Polizzotto MN, Lundgren JD, Gardner EM; INSIGHT START Study Group. Incomplete ART adherence is associated with higher inflammation in individuals who achieved virologic suppression in the START study. J Int AIDS Soc. 2019 Jun;22(6):e25297. doi: 10.1002/jia2.25297.

Reference Type DERIVED
PMID: 31250552 (View on PubMed)

Borges AH, Neuhaus J, Sharma S, Neaton JD, Henry K, Anagnostou O, Staub T, Emery S, Lundgren JD; INSIGHT SMART; START Study Groups. The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis. J Infect Dis. 2019 Jan 7;219(2):254-263. doi: 10.1093/infdis/jiy442.

Reference Type DERIVED
PMID: 30032171 (View on PubMed)

Molina JM, Grund B, Gordin F, Williams I, Schechter M, Losso M, Law M, Ekong E, Mwelase N, Skoutelis A, Wiselka MJ, Vandekerckhove L, Benfield T, Munroe D, Lundgren JD, Neaton JD; INSIGHT START study group. Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate initiation of antiretroviral therapy? A post-hoc subgroup analysis of the START trial. Lancet HIV. 2018 Apr;5(4):e172-e180. doi: 10.1016/S2352-3018(18)30003-1. Epub 2018 Jan 16.

Reference Type DERIVED
PMID: 29352723 (View on PubMed)

Ronit A, Sharma S, Baker JV, Mngqibisa R, Delory T, Caldeira L, Ndembi N, Lundgren JD, Phillips AN; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Strategic Timing of Antiretroviral Treatment (START) Study Group. Serum Albumin as a Prognostic Marker for Serious Non-AIDS Endpoints in the Strategic Timing of Antiretroviral Treatment (START) Study. J Infect Dis. 2018 Jan 17;217(3):405-412. doi: 10.1093/infdis/jix350.

Reference Type DERIVED
PMID: 29244111 (View on PubMed)

Baker JV, Sharma S, Achhra AC, Bernardino JI, Bogner JR, Duprez D, Emery S, Gazzard B, Gordin J, Grandits G, Phillips AN, Schwarze S, Soliman EZ, Spector SA, Tambussi G, Lundgren J; INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) START (Strategic Timing of Antiretroviral Treatment) Study Group. Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial. J Am Heart Assoc. 2017 May 22;6(5):e004987. doi: 10.1161/JAHA.116.004987.

Reference Type DERIVED
PMID: 28533305 (View on PubMed)

Grady C, Touloumi G, Walker AS, Smolskis M, Sharma S, Babiker AG, Pantazis N, Tavel J, Florence E, Sanchez A, Hudson F, Papadopoulos A, Emanuel E, Clewett M, Munroe D, Denning E; INSIGHT START Informed Consent Substudy Group. A randomized trial comparing concise and standard consent forms in the START trial. PLoS One. 2017 Apr 26;12(4):e0172607. doi: 10.1371/journal.pone.0172607. eCollection 2017.

Reference Type DERIVED
PMID: 28445471 (View on PubMed)

O'Connor J, Vjecha MJ, Phillips AN, Angus B, Cooper D, Grinsztejn B, Lopardo G, Das S, Wood R, Wilkin A, Klinker H, Kantipong P, Klingman KL, Jilich D, Herieka E, Denning E, Abubakar I, Gordin F, Lundgren JD; INSIGHT START study group. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per muL: secondary outcome results from a randomised controlled trial. Lancet HIV. 2017 Mar;4(3):e105-e112. doi: 10.1016/S2352-3018(16)30216-8. Epub 2017 Jan 5.

Reference Type DERIVED
PMID: 28063815 (View on PubMed)

Larson GS, Carey C, Grarup J, Hudson F, Sachi K, Vjecha MJ, Gordin F; INSIGHT Group. Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials. Clin Trials. 2016 Apr;13(2):127-36. doi: 10.1177/1740774515625974. Epub 2016 Feb 8.

Reference Type DERIVED
PMID: 26908541 (View on PubMed)

Carr A, Grund B, Neuhaus J, Schwartz A, Bernardino JI, White D, Badel-Faesen S, Avihingsanon A, Ensrud K, Hoy J; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Prevalence of and risk factors for low bone mineral density in untreated HIV infection: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):137-46. doi: 10.1111/hiv.12242.

Reference Type DERIVED
PMID: 25711332 (View on PubMed)

Matthews GV, Neuhaus J, Bhagani S, Mehta SH, Vlahakis E, Doroana M, Naggie S, Arenas-Pinto A, Peters L, Rockstroh JK; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Baseline prevalence and predictors of liver fibrosis among HIV-positive individuals: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(Suppl 1):129-36. doi: 10.1111/hiv.12241.

Reference Type DERIVED
PMID: 25711331 (View on PubMed)

Kunisaki KM, Niewoehner DE, Collins G, Nixon DE, Tedaldi E, Akolo C, Kityo C, Klinker H, La Rosa A, Connett JE; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Pulmonary function in an international sample of HIV-positive, treatment-naive adults with CD4 counts > 500 cells/muL: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 0):119-28. doi: 10.1111/hiv.12240.

Reference Type DERIVED
PMID: 25711330 (View on PubMed)

Baker JV, Engen NW, Huppler Hullsiek K, Stephan C, Jain MK, Munderi P, Pett S, Duprez D; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Assessment of arterial elasticity among HIV-positive participants with high CD4 cell counts: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):109-18. doi: 10.1111/hiv.12239.

Reference Type DERIVED
PMID: 25711329 (View on PubMed)

Wright EJ, Grund B, Cysique LA, Robertson KR, Brew BJ, Collins G, Shlay JC, Winston A, Read TR, Price RW; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Factors associated with neurocognitive test performance at baseline: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1:97-108. doi: 10.1111/hiv.12238.

Reference Type DERIVED
PMID: 25711328 (View on PubMed)

Lifson AR, Grandits GA, Gardner EM, Wolff MJ, Pulik P, Williams I, Burman WJ; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Quality of life assessment among HIV-positive persons entering the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):88-96. doi: 10.1111/hiv.12237.

Reference Type DERIVED
PMID: 25711327 (View on PubMed)

Baxter JD, Dunn D, White E, Sharma S, Geretti AM, Kozal MJ, Johnson MA, Jacoby S, Llibre JM, Lundgren J; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):77-87. doi: 10.1111/hiv.12236.

Reference Type DERIVED
PMID: 25711326 (View on PubMed)

Rodger AJ, Lampe FC, Grulich AE, Fisher M, Friedland G, Phanuphak N, Bogner JR, Pereira LC, Rietmeijer C, Burman W, Phillips AN; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Transmission risk behaviour at enrolment in participants in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 0):64-76. doi: 10.1111/hiv.12235.

Reference Type DERIVED
PMID: 25711325 (View on PubMed)

Achhra AC, Mocroft A, Ross MJ, Ryom L, Lucas GM, Furrer H, Neuhaus J, Somboonwit C, Kelly M, Gatell JM, Wyatt CM; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Kidney disease in antiretroviral-naive HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):55-63. doi: 10.1111/hiv.12234.

Reference Type DERIVED
PMID: 25711324 (View on PubMed)

Soliman EZ, Sharma S, Arasteh K, Wohl D, Achhra A, Tambussi G, O'Connor J, Stein JH, Duprez DA, Neaton JD, Phillips A; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 0):46-54. doi: 10.1111/hiv.12233.

Reference Type DERIVED
PMID: 25711323 (View on PubMed)

Law MG, Achhra A, Deeks SG, Gazzard B, Migueles SA, Novak RM, Ristola M; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):37-45. doi: 10.1111/hiv.12232.

Reference Type DERIVED
PMID: 25711322 (View on PubMed)

Sharma S, Babiker AG, Emery S, Gordin FM, Lundgren JD, Neaton JN, Bakowska E, Schechter M, Wiselka MJ, Wolff MJ; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):30-6. doi: 10.1111/hiv.12231.

Reference Type DERIVED
PMID: 25711321 (View on PubMed)

Denning E, Sharma S, Smolskis M, Touloumi G, Walker S, Babiker A, Clewett M, Emanuel E, Florence E, Papadopoulos A, Sanchez A, Tavel J, Grady C; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Reported consent processes and demographics: a substudy of the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):24-9. doi: 10.1111/hiv.12230.

Reference Type DERIVED
PMID: 25711320 (View on PubMed)

Grarup J, Rappoport C, Engen NW, Carey C, Hudson F, Denning E, Sharma S, Florence E, Vjecha MJ; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(Suppl Suppl 1):14-23. doi: 10.1111/hiv.12229.

Reference Type DERIVED
PMID: 25711319 (View on PubMed)

Geffen N, Aagaard P, Corbelli GM, Meulbroek M, Peavy D, Rappoport C, Schwarze S, Collins S; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) Community Advisory Board. Community perspective on the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):10-3. doi: 10.1111/hiv.12228.

Reference Type DERIVED
PMID: 25711318 (View on PubMed)

INSIGHT Strategic Timing of AntiRetroviral Treatment (START) Study Group; Lundgren J, Babiker A, Gordin F, Emery S, Fatkenheuer G, Molina JM, Wood R, Neaton JD. Why START? Reflections that led to the conduct of this large long-term strategic HIV trial. HIV Med. 2015 Apr;16 Suppl 1(0 1):1-9. doi: 10.1111/hiv.12227. No abstract available.

Reference Type DERIVED
PMID: 25711317 (View on PubMed)

Kunisaki KM, Quick H, Baker JV. HIV antiretroviral therapy reduces circulating surfactant protein-D levels. HIV Med. 2011 Oct;12(9):580-1. doi: 10.1111/j.1468-1293.2011.00920.x. No abstract available.

Reference Type DERIVED
PMID: 21951596 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

Access external resources that provide additional context or updates about the study.

http://www.insight-trials.org

INSIGHT network website, including information on the START trial

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

U01AI068641

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2008-006439-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0603M83587

Identifier Type: -

Identifier Source: org_study_id

NCT00821171

Identifier Type: -

Identifier Source: nct_alias

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