Strategic Timing of Antiretroviral Treatment

HIV Infection Clinical Trial

— START  

Official title:

Strategic Timing of AntiRetroviral Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00867048
• Other study ID #: 0603M83587
• Secondary ID: U01AI0686412008-
• Status: Completed
• Phase: Phase 4
• Start date: April 15, 2009
• Est. completion date: July 27, 2022

Study information

• Verified date: February 2024
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00821171

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4688
• Est. completion date: July 27, 2022
• Est. primary completion date: July 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections
• Infections

Intervention

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.

Locations

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

Sponsors (22)

Lead Sponsor

Collaborator

University of Minnesota

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

Countries where clinical trial is conducted

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 & Publications (2)

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. — View 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 o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Endpoint of AIDS, Serious Non-AIDS Diagnoses, and All-cause Mortality		full follow-up, 9.3 years
Secondary	AIDs or AIDs Related Death	participant count	full follow-up, 9.3 years
Secondary	Specific Non-AIDS Diagnoses		full follow-up, 9.3 years
Secondary	Death, All-cause Mortality	Count of participants	full follow-up, 9.3 years
Secondary	Quality of Life- Mean Change From Baseline in a Visual Analog Scale (VAS) for Perceived Current Health	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
Secondary	Transmission Risk Behavior Outcome 1	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
Secondary	Change in Neurocognitive Function (in a Subset of Participants)	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
Secondary	Large Artery Elasticity (in a Subset of Participants)	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
Secondary	Rate of Lung Function Decline (in a Subset of Participants) Among	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
Secondary	Changes in Bone Mineral Density (in a Subset of Participants) Measure 1	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
Secondary	Transmission Risk Behavior Outcome 2	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
Secondary	Small Artery Elasticity (in a Subset of Participants)	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
Secondary	Rate of Lung Function Decline (in a Subset of Participants) Among Non-smokers	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
Secondary	Changes in Bone Mineral Density (in a Subset of Participants) Measure 2	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

External Links

•   INSIGHT network website, including information on the START trial