Clinical trial NCT00867048: Strategic Timing of Antiretroviral Treatment
Official title: Strategic Timing of AntiRetroviral Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infection
Keywords: highly active antiretroviral therapy (HAART)
CD4 Count
Early Intervention
HIV
HIV Infection
HIV Infections
treatment naive
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Copenhagen HIV Programme (CHIP) -- Copenhagen, Denmark
name: Medical Research Council
name: Kirby Institute
name: Washington D.C. Veterans Affairs Medical Center
name: ANRS, Emerging Infectious Diseases
name: German Federal Ministry of Education and Research
name: NEAT - European AIDS Treatment Network
name: National Health and Medical Research Council, Australia
name: National Institutes of Health Clinical Center (CC)
name: National Cancer Institute (NCI)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Institute of Mental Health (NIMH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Abbott
name: Bristol-Myers Squibb
name: Gilead Sciences
name: GlaxoSmithKline
name: Merck Sharp & Dohme LLC
name: Tibotec Pharmaceutical Limited
First posted: 2009-03-23
Enrollment: 4688
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Composite Endpoint of AIDS, Serious Non-AIDS Diagnoses, and All-cause Mortality
timeFrame: full follow-up, 9.3 years
Secondary outcomes:
measure: AIDs or AIDs Related Death
timeFrame: full follow-up, 9.3 years
measure: Specific Non-AIDS Diagnoses
timeFrame: full follow-up, 9.3 years
measure: Death, All-cause Mortality
timeFrame: full follow-up, 9.3 years
measure: Quality of Life- Mean Change From Baseline in a Visual Analog Scale (VAS) for Perceived Current Health
timeFrame: 4.5 years
measure: Transmission Risk Behavior Outcome 1
timeFrame: 12 months
measure: Change in Neurocognitive Function (in a Subset of Participants)
timeFrame: 4.5 years
measure: Large Artery Elasticity (in a Subset of Participants)
timeFrame: 4.5 years
measure: Rate of Lung Function Decline (in a Subset of Participants) Among
timeFrame: 4.5 years
measure: Changes in Bone Mineral Density (in a Subset of Participants) Measure 1
timeFrame: 4.5 years
measure: Transmission Risk Behavior Outcome 2
timeFrame: 12 month visit
measure: Small Artery Elasticity (in a Subset of Participants)
timeFrame: 4.5 years
measure: Rate of Lung Function Decline (in a Subset of Participants) Among Non-smokers
timeFrame: 4.5 years
measure: Changes in Bone Mineral Density (in a Subset of Participants) Measure 2
timeFrame: 4.5 years
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Los Angeles
country: United States
facility: UCLA CARE-4-Families (LABAC CRS)
state: California
city: San Diego
country: United States
facility: UCSD Mother-Child-Adolescent Program
state: California
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
city: Denver
country: United States
facility: Denver Public Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: George Washington Medical Faculty Associates
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VA Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida Health Services Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida, Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: Florida Department of Health in Orange County/Sunshine Care Center
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates NW FL, PA
state: Florida
city: Tampa
country: United States
facility: Hillsborough County Health Deptment/University of South Florida
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research and Treatment Center of the Treasure Coast
state: Florida
city: Chicago
country: United States
facility: Mt. Sinai Hospital
state: Illinois
city: Chicago
country: United States
facility: Lurie Children's Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
city: Boston
country: United States
facility: Community Research Initiative of New England
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Southfield
country: United States
facility: Newland Immunology Center of Excellence (NICE)
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Newark
country: United States
facility: New Jersey Medical School Adult Clinical Research Center
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Cornell CRS
state: New York
city: Chapel Hill
country: United States
facility: UNC AIDS Clinical Trials Unit
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease
state: North Carolina
city: Raleigh
country: United States
facility: Wake County Human Services
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: The Research + Education Group - Portland
state: Oregon
city: Portland
country: United States
facility: The Research and Education Group at Portland VA Research Foundation
state: Oregon
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Clinical Research Unit
state: Texas
city: Fort Worth
country: United States
facility: University of North Texas Health Science Center
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: San Antonio Military Health System
state: Texas
city: Portsmouth
country: United States
facility: Naval Medical Center Portsmouth
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: AIDS Resource Center of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: El Palomar
country: Argentina
facility: Hospital Nacional Profesor Alejandro Posadas
state: Buenos Aires
city: Isidro Casanova
country: Argentina
facility: Hospital Interzonal General de Agudos Dr. Diego Paroissien
state: Buenos Aires
city: Rosario
country: Argentina
facility: CAICI (Instituto Centralizado de Assistencia e Investigacion Clinica Integral)
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: FUNCEI
city: Buenos Aires
country: Argentina
facility: Fundacion IDEAA
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos JM Ramos Mejia
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Hospital Rawson
city: Neuquen
country: Argentina
facility: CEIN
city: Burwood
country: Australia
facility: Burwood Road General Practice
state: New South Wales
city: Darlinghurst
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Sexual Health and HIV Service - Clinic 2
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Melbourne Sexual Health Centre
state: Victoria
city: Melbourne
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: St Kilda
country: Australia
facility: Centre Clinic
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Vienna
country: Austria
facility: Otto-Wagner-Spital SMZ /Baumgartner Hoehe
city: Vienna
country: Austria
facility: University Vienna General Hospital
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire St. Pierre (C.H.U. St. Pierre)
city: Ghent
country: Belgium
facility: Universitaire Ziekenhuizen Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Gasthuisberg
city: Salvador
country: Brazil
facility: SEI - Servi�os Especializados em Infectologia
state: BA
city: Vitoria
country: Brazil
facility: Center for Infectious Diseases at the UFES
state: ES
city: Rio de Janeiro
country: Brazil
facility: Hospital Escola Sao Francisco de Assis - UFRJ
state: RJ
city: Rio de Janeiro
country: Brazil
facility: Ipec/Fiocruz
state: RJ
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emilio Ribas - IIER
state: SP
city: Sao Paulo
country: Brazil
facility: Centro de Referencia e Treinamento DST/Aids
state: SP
city: Sao Paulo
country: Brazil
facility: Lim 56/Hcfmusp
state: SP
city: Santiago
country: Chile
facility: Fundacion Arriaran
city: Plzen
country: Czechia
facility: University Hospital Plzen, CZ
city: Prague
country: Czechia
facility: Faculty Hospital Na Bulovce, Prague, Czech Rep.
city: Aarhus
country: Denmark
facility: Arhus Universitetshospital, Skejby
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Infektionsmedicinsk ambulatorium 8622
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital, Department of Infectious Diseases
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital Infectious Diseases
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, Div. of Infectious Diseases CRS
city: Besancon
country: France
facility: CHU de Besan�on - H�pital Jean-Minjoz
city: Caen
country: France
facility: CHU C�te de Nacre
city: Clamart
country: France
facility: H�pital Antoine Becl�re
city: Creteil
country: France
facility: H�pital Henri Mondor
city: Le Kremlin-Bicetre
country: France
facility: H�pital de Bicetre
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetri�re
city: Paris
country: France
facility: H�pital Europeen Georges Pompidou
city: Paris
country: France
facility: H�pital H�tel Dieu
city: Paris
country: France
facility: H�pital Saint-Antoine
city: Paris
country: France
facility: H�pital Saint-Louis
city: Suresnes
country: France
facility: H�pital Foch
city: Tourcoing
country: France
facility: Centre Hospitalier - H�pital Gustave Dron
city: Berlin
country: Germany
facility: EPIMED-Gesellschaft fur epidemiologische und klinische Forschung in der MedizinmbH
city: Berlin
country: Germany
facility: Gemeinschaftspraxis Jessen-Jessen-Stein
city: Bonn
country: Germany
facility: Medizinische Universitatsklinik - Bonn, Immunologische Ambulanz CRS
city: Cologne
country: Germany
facility: Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Duesseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Essen
country: Germany
facility: Klinik fur Dermatologie, Venerologie, Allergologie
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe - University Hospital, Infektionsambulanz CRS
city: Hamburg
country: Germany
facility: ICH Study Center
city: Hamburg
country: Germany
facility: Ifi - Studien und Projekte GmbH
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Munich
country: Germany
facility: Klinikum der Universitat Munchen
city: Regensburg
country: Germany
facility: Universitatsklinikum Regensburg
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg, Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie CRS
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Athens
country: Greece
facility: Evangelismos General Hospital
city: Athens
country: Greece
facility: Hippokration University General Hospital of Athens
city: Athens
country: Greece
facility: Korgialenio-Benakio Hellenic Red Cross
city: Athens
country: Greece
facility: Syngros Hospital
city: Thessaloniki
country: Greece
facility: AHEPA University Hospital
city: Pune
country: India
facility: Institute of Infectious Diseases
state: Maharashtra
city: Chennai
country: India
facility: YRGCARE Medical Centre VHS, Chennai CRS
state: Tamil Nadu
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milan
country: Italy
facility: Ospedale San Raffaele S.r.l.
state: MI
city: Rome
country: Italy
facility: Lazzaro Spallanzani IRCSS
state: RM
city: Luxembourg
country: Luxembourg
facility: Centre Hospitalier de Luxembourg
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Federal Territory
city: Bamako
country: Mali
facility: Serefo/Cesac Mali
city: Tlalpan
country: Mexico
facility: INCMNSZ (Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran)
city: Casablanca
country: Morocco
facility: University Hospital Centre Ibn Rochd
city: Abuja
country: Nigeria
facility: Institute of Human Virology-Nigeria (IHVN)
state: FCT
city: Oslo
country: Norway
facility: Oslo University Hospital, Ulleval
city: Lima
country: Peru
facility: Via Libre
city: Lima
country: Peru
facility: Asociacion Civil IMPACTA Salud y Educacion
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: Lima
country: Peru
facility: Asociacion Civil Impacta Salud y Educacion - Sede San Miguel
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny
city: Warsaw
country: Poland
facility: Wojewodzki Szpital Zakazny
city: Wroclaw
country: Poland
facility: EMC Instytut Medyczny SA
city: Lisbon
country: Portugal
facility: Hospital Curry Cabral
city: Lisbon
country: Portugal
facility: Hospital de Egas Moniz
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria
city: Oporto
country: Portugal
facility: Hospital Joaquim Urbano
city: Rio Piedras
country: Puerto Rico
facility: San Juan Hospital
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Pediatric Research Site
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS Clinical Trials Unit (PR-ACTU)
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation Clinical Trials Unit
city: Durban
country: South Africa
facility: Durban International Clinical Research Site (WWH)
city: Durban
country: South Africa
facility: Durban International Clinical Research Site
city: Johannesburg
country: South Africa
facility: CHRU
city: Pretoria
country: South Africa
facility: 1 Military Hospital
city: Alcala de Henares
country: Spain
facility: Hospital Universitario Principe de Asturias
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital La Princesa, Internal Medicine and Infectious Disease Service CRS
city: Madrid
country: Spain
facility: Hospital Universitario Doce de Octubre
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Vigo
country: Spain
facility: Complejo Hospitalario Xeral Cies
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Malmo
country: Sweden
facility: Skane University Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: Bern University Hospital
city: Geneva
country: Switzerland
facility: Unite VIH/SIDA Geneva
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Bangkok Noi
country: Thailand
facility: Siriraj Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Chiang Mai
country: Thailand
facility: Sanpatong Hospital
city: Chiang Mai
country: Thailand
facility: Research Institute for Health Sciences (RIHES)
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
city: Chon Buri
country: Thailand
facility: Chonburi Regional Hospital
city: Khon Kaen
country: Thailand
facility: Khon Kaen University, Srinagarind Hospital
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Institute
city: Entebbe
country: Uganda
facility: MRC/UVRI Research Unit on AIDS
city: Kampala
country: Uganda
facility: Joint Clinical Research Center (JCRC)
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
state: Berkshire
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
state: Cleveland
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
state: East Sussex
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: Leicestershire
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust (RVH)
state: Northern Ireland
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospital NHS Foundation Trust
state: South Yorkshire
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
state: West Midlands
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: West Midlands
city: Coventry
country: United Kingdom
facility: Coventry and Warwickshire NHS partnership Trust
state: West Midlands
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St.Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Lewisham and Greenwich NHS Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: St. George's Healthcare NHS Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: University College London Medical School
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital
Study officials:
affiliation: University of Minnesota
name: James D Neaton, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Research Council Clinical Trials Unit, London
name: Abdel Babiker, PhD
role: STUDY_CHAIR
affiliation: Copenhagen HIV Programme
name: Jens Lundgren, MD, DMSc
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.