Strategic Timing of Antiretroviral Treatment (START)

February 29, 2024 updated by: University of Minnesota

Strategic Timing of AntiRetroviral Treatment

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

4688

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Hospital Italiano de Buenos Aires
      • Buenos Aires, Argentina
        • FUNCEI
      • Buenos Aires, Argentina
        • Fundacion IDEAA
      • Buenos Aires, Argentina
        • Hospital General de Agudos JM Ramos Mejía
      • Cordoba, Argentina
        • Hospital Rawson
      • Neuquen, Argentina
        • CEIN
    • Buenos Aires
      • El Palomar, Buenos Aires, Argentina
        • Hospital Nacional Profesor Alejandro Posadas
      • Isidro Casanova, Buenos Aires, Argentina
        • Hospital Interzonal General de Agudos Dr. Diego Paroissien
    • Santa Fe
      • Rosario, Santa Fe, Argentina
        • CAICI (Instituto Centralizado de Assistencia e Investigacion Clinica Integral)
  • Australia
    • New South Wales
      • Burwood, New South Wales, Australia, 2134
        • Burwood Road General Practice
      • Darlinghurst, New South Wales, Australia, 2010
        • Holdsworth House Medical Practice
      • Darlinghurst, New South Wales, Australia, 2010
        • East Sydney Doctors
      • Darlinghurst, New South Wales, Australia, 2010
        • St. Vincent's Hospital
      • Darlinghurst, New South Wales, Australia, 2010
        • Taylor Square Private Clinic
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • Queensland
      • Brisbane, Queensland, Australia, 4000
        • Sexual Health and HIV Service - Clinic 2
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • The Alfred Hospital
      • Melbourne, Victoria, Australia, 3053
        • Melbourne Sexual Health Centre
      • Melbourne, Victoria, Australia, 3181
        • Prahran Market Clinic
      • St Kilda, Victoria, Australia, 3182
        • Centre Clinic
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
  • Austria
      • Vienna, Austria
        • Otto-Wagner-Spital SMZ /Baumgartner Hoehe
      • Vienna, Austria
        • University Vienna General Hospital
  • Belgium
      • Antwerp, Belgium
        • Institute of Tropical Medicine
      • Brussels, Belgium
        • Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre)
      • Ghent, Belgium
        • Universitaire Ziekenhuizen Gent
      • Leuven, Belgium
        • Universitair Ziekenhuis Gasthuisberg
  • Brazil
    • BA
      • Salvador, BA, Brazil, 40110-010
        • SEI - Servi�os Especializados em Infectologia
    • ES
      • Vitoria, ES, Brazil, 29040-091
        • Center for Infectious Diseases at the UFES
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20210-030
        • Hospital Escola Sao Francisco de Assis - UFRJ
      • Rio de Janeiro, RJ, Brazil, 21040-900
        • Ipec/Fiocruz
    • SP
      • Sao Paulo, SP, Brazil, 04121-000
        • Centro de Referência e Treinamento DST/AIDS
      • Sao Paulo, SP, Brazil, 01246-900
        • Instituto de Infectologia Emilio Ribas - IIER
      • Sao Paulo, SP, Brazil, 05403-000
        • Lim 56/Hcfmusp
  • Chile
      • Santiago, Chile
        • Fundacion Arriaran
  • Czechia
      • Plzen, Czechia
        • University Hospital Plzen, CZ
      • Prague, Czechia
        • Faculty Hospital Na Bulovce, Prague, Czech Rep.
  • Denmark
      • Aarhus, Denmark
        • Arhus Universitetshospital, Skejby
      • Copenhagen, Denmark
        • Rigshospitalet, Infektionsmedicinsk ambulatorium 8622
      • Hvidovre, Denmark
        • Hvidovre University Hospital, Department of Infectious Diseases
      • Odense, Denmark
        • Odense University Hospital
  • Estonia
      • Tallinn, Estonia
        • West Tallinn Central Hospital Infectious Diseases
  • Finland
      • Helsinki, Finland
        • Helsinki University Central Hospital, Div. of Infectious Diseases CRS
  • France
      • Besancon, France
        • CHU de Besan�on - H�pital Jean-Minjoz
      • Caen, France
        • CHU C�te de Nacre
      • Clamart, France
        • H�pital Antoine Becl�re
      • Creteil, France
        • H�pital Henri Mondor
      • Le Kremlin-Bicetre, France
        • H�pital de Bicetre
      • Paris, France
        • Groupe Hospitalier Pitie-Salpetri�re
      • Paris, France
        • H�pital Europeen Georges Pompidou
      • Paris, France
        • H�pital H�tel Dieu
      • Paris, France
        • H�pital Saint-Antoine
      • Paris, France
        • H�pital Saint-Louis
      • Suresnes, France
        • H�pital Foch
      • Tourcoing, France
        • Centre Hospitalier - H�pital Gustave Dron
  • Germany
      • Berlin, Germany
        • EPIMED-Gesellschaft fur epidemiologische und klinische Forschung in der MedizinmbH
      • Berlin, Germany
        • Gemeinschaftspraxis Jessen-Jessen-Stein
      • Bonn, Germany
        • Medizinische Universitatsklinik - Bonn, Immunologische Ambulanz CRS
      • Cologne, Germany
        • Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV
      • Dortmund, Germany
        • Klinikum Dortmund gGmbH
      • Duesseldorf, Germany
        • Universitätsklinikum Düsseldorf
      • Erlangen, Germany
        • Universitatsklinikum Erlangen
      • Essen, Germany
        • Klinik fur Dermatologie, Venerologie, Allergologie
      • Frankfurt, Germany
        • Johann Wolfgang Goethe - University Hospital, Infektionsambulanz CRS
      • Hamburg, Germany
        • Universitätsklinikum Hamburg-Eppendorf
      • Hamburg, Germany
        • ICH Study Center
      • Hamburg, Germany
        • Ifi - Studien und Projekte GmbH
      • Hanover, Germany
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany
        • Universitätsklinikum Heidelberg
      • Munich, Germany
        • Klinikum der Universität München
      • Regensburg, Germany
        • Universitätsklinikum Regensburg
      • Wuerzburg, Germany
        • Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie CRS
  • Greece
      • Athens, Greece
        • Attikon University General Hospital
      • Athens, Greece
        • Evangelismos General Hospital
      • Athens, Greece
        • Hippokration University General Hospital of Athens
      • Athens, Greece
        • Korgialenio-Benakio Hellenic Red Cross
      • Athens, Greece
        • Syngros Hospital
      • Thessaloniki, Greece
        • Ahepa University Hospital
  • India
    • Maharashtra
      • Pune, Maharashtra, India, 411037
        • Institute of Infectious Diseases
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 600113
        • YRGCARE Medical Centre VHS, Chennai CRS
  • Ireland
      • Dublin, Ireland
        • Mater Misericordiae University Hospital
  • Israel
      • Haifa, Israel
        • Rambam Medical Center
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center
  • Italy
    • MI
      • Milan, MI, Italy
        • Ospedale San Raffaele s.r.l.
    • RM
      • Rome, RM, Italy
        • Lazzaro Spallanzani IRCSS
  • Luxembourg
      • Luxembourg, Luxembourg
        • Centre Hospitalier de Luxembourg
  • Malaysia
    • Federal Territory
      • Kuala Lumpur, Federal Territory, Malaysia
        • University Malaya Medical Centre
  • Mali
      • Bamako, Mali
        • Serefo/Cesac Mali
  • Mexico
      • Tlalpan, Mexico
        • INCMNSZ (Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran)
  • Morocco
      • Casablanca, Morocco, 20360
        • University Hospital Centre Ibn Rochd
  • Nigeria
    • FCT
      • Abuja, FCT, Nigeria
        • Institute of Human Virology-Nigeria (IHVN)
  • Norway
      • Oslo, Norway
        • Oslo University Hospital, Ullevål
  • Peru
      • Lima, Peru, 13
        • Hospital Nacional Guillermo Almenara Irigoyen
      • Lima, Peru, 11
        • Hospital Nacional Edgardo Rebagliati Martins
      • Lima, Peru, 01
        • Via Libre
      • Lima, Peru, 04
        • Asociacion Civil IMPACTA Salud y Educacion
      • Lima, Peru, 32
        • Asociacion Civil Impacta Salud y Educacion - Sede San Miguel
  • Poland
      • Bialystok, Poland
        • Uniwersytecki Szpital Kliniczny
      • Warsaw, Poland
        • Wojewodzki Szpital Zakazny
      • Wroclaw, Poland
        • EMC Instytut Medyczny SA
  • Portugal
      • Lisbon, Portugal
        • Hospital de Santa Maria
      • Lisbon, Portugal
        • Hospital Curry Cabral
      • Lisbon, Portugal
        • Hospital de Egas Moniz
      • Oporto, Portugal
        • Hospital Joaquim Urbano
  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • San Juan Hospital
      • San Juan, Puerto Rico, 00935-6528
        • University of Puerto Rico Pediatric Research Site
      • San Juan, Puerto Rico, 00935
        • Puerto Rico-AIDS Clinical Trials Unit (PR-ACTU)
  • South Africa
      • Cape Town, South Africa
        • Desmond Tutu HIV Foundation Clinical Trials Unit
      • Durban, South Africa
        • Durban International Clinical Research Site (WWH)
      • Durban, South Africa
        • Durban International Clinical Research Site
      • Johannesburg, South Africa
        • CHRU
      • Pretoria, South Africa
        • 1 Military Hospital
  • Spain
      • Alcala de Henares, Spain
        • Hospital Universitario Príncipe de Asturias
      • Badalona, Spain
        • Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spain
        • Hospital Clínic de Barcelona
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
      • Madrid, Spain
        • Hospital La Paz
      • Madrid, Spain
        • Hospital Clínico San Carlos
      • Madrid, Spain
        • Hospital Universitario Doce de Octubre
      • Madrid, Spain
        • Hospital La Princesa, Internal Medicine and Infectious Disease Service CRS
      • Terrassa, Spain
        • Hospital Universitari Mutua Terrassa
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
      • Vigo, Spain
        • Complejo Hospitalario Xeral Cies
  • Sweden
      • Gothenburg, Sweden
        • Sahlgrenska University Hospital
      • Malmo, Sweden
        • Skane University Hospital
  • Switzerland
      • Basel, Switzerland
        • University Hospital Basel
      • Bern, Switzerland
        • Bern University Hospital
      • Geneva, Switzerland
        • Unite VIH/SIDA Geneva
      • Zurich, Switzerland
        • University Hospital Zurich
  • Thailand
      • Bangkok, Thailand, 10400
        • Ramathibodi Hospital
      • Bangkok, Thailand, 10330
        • Chulalongkorn University Hospital
      • Bangkok Noi, Thailand, 10700
        • Siriraj Hospital
      • Chiang Mai, Thailand, 50120
        • Sanpatong Hospital
      • Chiang Mai, Thailand, 50200
        • Research Institute for Health Sciences (RIHES)
      • Chiang Rai, Thailand, 57000
        • Chiangrai Prachanukroh Hospital
      • Chon Buri, Thailand, 20000
        • Chonburi Regional Hospital
      • Khon Kaen, Thailand, 40002
        • Khon Kaen University, Srinagarind Hospital
      • Nonthaburi, Thailand, 11000
        • Bamrasnaradura Institute
  • Uganda
      • Entebbe, Uganda
        • MRC/UVRI Research Unit on AIDS
      • Kampala, Uganda
        • Joint Clinical Research Center (JCRC)
  • United Kingdom
      • Bristol, United Kingdom, BS10 5NB
        • Southmead Hospital
      • Gloucester, United Kingdom, GL1 3NN
        • Gloucestershire Royal Hospital
      • London, United Kingdom, NW3 2QG
        • Royal Free London NHS Foundation Trust
      • London, United Kingdom, SW10 9NH
        • Chelsea And Westminster Hospital
      • London, United Kingdom, E1 1BB
        • Barts Health NHS Trust
      • London, United Kingdom, W2 1NY
        • Imperial College Healthcare NHS Trust
      • London, United Kingdom, SE18 4QH
        • Lewisham and Greenwich NHS Trust
      • London, United Kingdom, SW17 0QT
        • St. George's Healthcare NHS Trust
      • London, United Kingdom, SE1 7EH
        • Guy's and St.Thomas' NHS Foundation Trust
      • London, United Kingdom, WC1E 6JB
        • University College London Medical School
      • Manchester, United Kingdom, M8 5RB
        • North Manchester General Hospital
    • Berkshire
      • Reading, Berkshire, United Kingdom, RG1 5LE
        • Royal Berkshire Hospital
    • Cleveland
      • Middlesbrough, Cleveland, United Kingdom, TS4 3BW
        • The James Cook University Hospital
    • Dorset
      • Bournemouth, Dorset, United Kingdom, BH7 7DW
        • Royal Bournemouth Hospital
    • East Sussex
      • Brighton, East Sussex, United Kingdom, BN2 1ES
        • Brighton and Sussex University Hospitals NHS Trust
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, BT12 6BA
        • Belfast Health and Social Care Trust (RVH)
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Sheffield Teaching Hospital NHS Foundation Trust
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital
      • Birmingham, West Midlands, United Kingdom, B15 2WB
        • Queen Elizabeth Hospital Birmingham
      • Coventry, West Midlands, United Kingdom, CV1 4FS
        • Coventry and Warwickshire NHS partnership Trust
  • United States
    • California
      • Alhambra, California, United States, 91803
        • University of Southern California
      • Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Healthcare System
      • Los Angeles, California, United States, 90095
        • UCLA CARE-4-Families (LABAC CRS)
      • San Diego, California, United States, 92103
        • UCSD Mother-Child-Adolescent Program
      • San Diego, California, United States, 92134-1201
        • Naval Medical Center San Diego
    • Colorado
      • Denver, Colorado, United States, 80204
        • Denver public Health
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School Of Medicine
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
      • Washington, District of Columbia, United States, 20422
        • Washington DC VA Medical Center
      • Washington, District of Columbia, United States, 20037
        • George Washington Medical Faculty Associates
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida, Jacksonville
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Services Center
      • Miami, Florida, United States, 33136
        • University of Miami
      • Orlando, Florida, United States, 32803
        • Orlando Immunology Center
      • Orlando, Florida, United States, 32805
        • Florida Department of Health in Orange County/Sunshine Care Center
      • Pensacola, Florida, United States, 32503
        • Infectious Diseases Associates NW FL, PA
      • Tampa, Florida, United States, 33602
        • Hillsborough County Health Deptment/University of South Florida
      • Vero Beach, Florida, United States, 32960
        • AIDS Research and Treatment Center of the Treasure Coast
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
      • Chicago, Illinois, United States, 60608
        • Mt. Sinai Hospital
      • Chicago, Illinois, United States, 60611-2605
        • Lurie Children's Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University Medical Center
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Boston, Massachusetts, United States, 02111
        • Community Research Initiative of New England
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Detroit, Michigan, United States, 48201
        • Wayne State University
      • Southfield, Michigan, United States, 48075
        • Newland Immunology Center of Excellence (NICE)
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital
      • Newark, New Jersey, United States, 07103
        • New Jersey Medical School Adult Clinical Research Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • Bronx, New York, United States, 10457
        • Bronx-Lebanon Hospital Center
      • New York, New York, United States, 10010
        • Cornell CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • UNC AIDS Clinical Trials Unit
      • Durham, North Carolina, United States, 27710
        • Duke University
      • Greensboro, North Carolina, United States, 27401-1209
        • Regional Center for Infectious Disease
      • Raleigh, North Carolina, United States, 27610
        • Wake County Human Services
      • Winston-Salem, North Carolina, United States, 27157-1042
        • Wake Forest University Health Sciences
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center
    • Oregon
      • Portland, Oregon, United States, 97210
        • The Research + Education Group - Portland
      • Portland, Oregon, United States, 97239
        • The Research and Education Group at Portland VA Research Foundation
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University
    • Tennessee
      • Memphis, Tennessee, United States, 38105-3678
        • St. Jude Children's Research Hospital
    • Texas
      • Dallas, Texas, United States, 75235
        • UT Southwestern Clinical Research Unit
      • Fort Worth, Texas, United States, 76107
        • University of North Texas Health Science Center
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
      • Houston, Texas, United States, 77030
        • Houston AIDS Research Team
      • San Antonio, Texas, United States, 78234
        • San Antonio Military Health System
    • Virginia
      • Portsmouth, Virginia, United States, 23708
        • Naval Medical Center Portsmouth
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College Of Wisconsin
      • Milwaukee, Wisconsin, United States, 53203
        • AIDS Resource Center of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early ART
Initiate ART immediately following randomization
Drug: 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.
Active Comparator: Deferred ART
Defer ART until the CD4+ count declines to <350 cells/cu mm or AIDS develops
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite Endpoint of AIDS, Serious Non-AIDS Diagnoses, and All-cause Mortality
Time Frame: full follow-up, 9.3 years
full follow-up, 9.3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life- Mean Change From Baseline in a Visual Analog Scale (VAS) for Perceived Current Health
Time Frame: 4.5 years
Mean change from baseline of the VAS. This was a single data item where participants self-reported their perceived current state of health on a scale of 0-100 (0=worst possible and 100=best possible).
4.5 years
Transmission Risk Behavior Outcome 1
Time Frame: 12 months
Proportion of participants identifying as men who have sex with men (MSM) engaging in condomless sex with HIV serodifferent partners (CLS-D) at study month 12. Participant completed a self-reported questionnaire on transmission risk behavior during the "past two months" at the month 12 visit following randomization.
12 months
Change in Neurocognitive Function (in a Subset of Participants)
Time Frame: 4.5 years
Mean change from baseline of the QNPZ-8 score. In the Neurology substudy of START, participants were administered a neuropsychological test battery of 8 tests (grooved peg board, finger tapping, Color Trails 1 and 2, Semantic Verbal Fluency, WAIS III Digit Symbol, HVLT-R Learning, HVLT-R Delayed Recall). Test scores were standardized to z-scores using baseline values as reference such that baseline values had a mean of 0 and standard deviation of 1. Test scores were standardized to z-scores using baseline values as reference such that baseline values had a mean of 0 and standard deviation of 1. Z-scores > 0 indicate improvement over baseline levels. The quantitative neuropsychological performance z-score (QNPZ-8) was the mean of the z-scores across the the 8 tests. Analyses were by intention-to-treat principles.
4.5 years
Large Artery Elasticity (in a Subset of Participants)
Time Frame: 4.5 years
Mean change from baseline in large arterial elasticity. In the Arterial Elasticity substudy of START, participants had non-invasive measurements of radial artery blood pressure waveforms recorded at baseline, study months 4, 8, and 12, and then annually. Small arterial elasticity (SAE) and large arterial elasticity (LAE) were derived from analysis of the diastolic pulse waveform. Analyses were by intention-to-treat principles.
4.5 years
Rate of Lung Function Decline (in a Subset of Participants) Among
Time Frame: 4.5 years
Rate of lung function decline (slope of forced expiratory volume (FEV1)) over follow-up among self-reported smokers at study entry. In the pulmonary substudy of START, participants had post-bronchodilator spirometry measures collected at baseline and annually. Analyses were by intention-to-treat principles.
4.5 years
Changes in Bone Mineral Density (in a Subset of Participants) Measure 1
Time Frame: 4.5 years
Mean percent change from baseline in bone mineral density at the spine. In the bone mineral density (BMD) substudy of START, participants underwent dual-enery x-ray absorptionmetry (DXA) to measure BMD at the spine and hip at baseline and annually. Analyses were by intention-to-treat principles.
4.5 years
Transmission Risk Behavior Outcome 2
Time Frame: 12 month visit
Percentage of participants identifying as hetrosexual engaging in condomless sex with HIV serodifferent partners (CLS-D) at study month 12. Participant completed a self-reported questionnaire on transmission risk behavior during the "past two months" at the month 12 visit following randomization.
12 month visit
Small Artery Elasticity (in a Subset of Participants)
Time Frame: 4.5 years
Mean change from baseline in small arterial elasticity. In the Arterial Elasticity substudy of START, participants had non-invasive measurements of radial artery blood pressure waveforms recorded at baseline, study months 4, 8, and 12, and then annually. Small arterial elasticity (SAE) and large arterial elasticity (LAE) were derived from analysis of the diastolic pulse waveform. Analyses were by intention-to-treat principles.
4.5 years
Rate of Lung Function Decline (in a Subset of Participants) Among Non-smokers
Time Frame: 4.5 years
Rate of lung function decline (slope of forced expiratory volume (FEV1)) over follow-up among self-reported non-smokers at study entry. In the pulmonary substudy of START, participants had post-bronchodilator spirometry measures collected at baseline and annually. Analyses were by intention-to-treat principles.
4.5 years
Changes in Bone Mineral Density (in a Subset of Participants) Measure 2
Time Frame: 4.5 years
Mean percent change from baseline in bone mineral density at the spine. In the bone mineral density (BMD) substudy of START, participants underwent dual-enery x-ray absorptionmetry (DXA) to measure BMD at the spine and hip at baseline and annually. Analyses were by intention-to-treat principles.
4.5 years
AIDs or AIDs Related Death
Time Frame: full follow-up, 9.3 years
participant count
full follow-up, 9.3 years
Specific Non-AIDS Diagnoses
Time Frame: full follow-up, 9.3 years
full follow-up, 9.3 years
Death, All-cause Mortality
Time Frame: full follow-up, 9.3 years
Count of participants
full follow-up, 9.3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

National Health and Medical Research Council, Australia
Bristol-Myers Squibb
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
GlaxoSmithKline
Merck Sharp & Dohme LLC
Gilead Sciences
National Institute of Neurological Disorders and Stroke (NINDS)
German Federal Ministry of Education and Research
Medical Research Council
Abbott
ANRS, Emerging Infectious Diseases
Washington D.C. Veterans Affairs Medical Center
The Kirby Institute for Infection and Immunity in Society
Tibotec Pharmaceutical Limited
Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark
NEAT - European AIDS Treatment Network

Investigators

  • Principal Investigator: James D Neaton, PhD, University of Minnesota
  • Study Chair: Abdel Babiker, PhD, Medical Research Council Clinical Trials Unit, London
  • Study Chair: Jens Lundgren, MD, DMSc, Copenhagen HIV Programme

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2009

Primary Completion (Actual)

July 27, 2022

Study Completion (Actual)

July 27, 2022

Study Registration Dates

First Submitted

March 20, 2009

First Submitted That Met QC Criteria

March 20, 2009

First Posted (Estimated)

March 23, 2009

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0603M83587
  • U01AI068641 (U.S. NIH Grant/Contract)
  • 2008-006439-12 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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