A Comparison of Two Ways to Manage Anti-HIV Treatment (The SMART Study)

HIV Infections Clinical Trial

Official title:

A Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027352
• Other study ID #: CPCRA 065
• Secondary ID: SMART
• Status: Completed
• Phase: N/A
• First received: December 4, 2001
• Last updated: November 24, 2009

Study information

• Verified date: December 2008
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to compare two ways of using anti-HIV drugs to help health care providers and patients decide how to best use anti-HIV treatments over many years. Many health care providers now treat patients with daily drugs to keep the viral load as low as possible. This approach helps patients with CD4 counts less than 200-250 cells/mm3 live longer without serious diseases. But it is not known if this is the best way to treat patients with higher CD4 counts. There is information suggesting that these patients may be able to wait to use anti-HIV drugs while CD4 counts are above 250 cells/mm3. Because this study will be carried out over several years, it will provide information on the long-term advantages and disadvantages of these two treatment strategies.

Description:

Implementation of antiretroviral treatment (ART) guidelines, which emphasize maximal and durable suppression of viral load for the majority of individuals infected with HIV, has resulted in a substantial decline in morbidity and mortality. However, many asymptomatic patients are not at immediate risk of serious opportunistic diseases, the effectiveness of ART wanes over time due to HIV drug resistance, and there are short- and long-term toxicities of treatment. This motivates a comparison of two strategies: one which conserves treatments by deferring their use while the risk of opportunistic disease is low and one which aims for sustained virologic suppression, irrespective of disease risk.

In this large, long-term trial, patients will be randomly assigned to either the drug conservation (DC) or viral suppression (VS) group. Patients will be enrolled over a 3-year period and followed for an average of 7.5 years. The DC group will stop or defer ART until CD4 cell count declines to below 250 cells/mm3; they will then receive treatment to increase CD4 count to greater than 350 cells/mm3 followed by episodic ART based on CD4 cell count. The VS group will use ART to maintain viral load as low as possible, irrespective of CD4 cell count. Patients will be seen Months 1, 2, 4, 6, 8, 10, and 12, then every 4 months for data collection visits. All available ARTs, including immunomodulators, and resistance testing may be used by patients in both treatment groups. Selected subsamples of patients enrolled in the study will be followed with more intensive data collection for secondary outcomes relating to cost and health care utilization, quality of life, HIV transmission risk behaviors, and metabolic complications of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

Note: Enrollment into this trial was halted 01/11/06.

Inclusion Criteria:

• HIV infection

• CD4 cell count greater than 350 cells/mm3 within 45 days of study entry

• Willing to start, change, or stop antiretroviral therapy

• Acceptable methods of contraception

• Good health at the time of study entry

• Available for the study for at least 6 months

• Able, in the clinician's opinion, to comply with the protocol

Exclusion Criteria:

• Currently participating in the MDR-HIV, NvR study, or another study which is not consistent with one of the treatment groups in this study. CPCRA FIRST participants may be screened for SMART after August 8, 2005 and can be randomized into SMART on or after September 19, 2005.

• Pregnant or breast-feeding

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Locations

Country	Name	City	State
Argentina	Hospital de Clinicas Jose de San Martin	Buenos Aires
Argentina	Hospital de Infecciosas F.J. Muniz	Buenos Aires
Argentina	Hospital Gn'l de Agudos JM Ramos Mejia	Buenos Aires
Argentina	Hospital Gn'l de Agudos T. Alvarez	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Rawson	Cordoba
Argentina	Hospital Interzonall de San Juan de Dios	La Plata
Argentina	Hospital Central	Mendoza
Argentina	CAICI	Rosario
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Burwood Street General Pratice	Burwood Nsw
Australia	Royal Perth Hosp	Perth
Australia	Alfred Hosp	Prahan
Australia	Royal Prince Alfred Hospital	Prahan
Australia	Prahran Market Clinic	South Yarra	Victoria
Australia	The Centre Clinic	South Yarra	Victoria
Australia	National Centre in HIV Epidemiology and Clinical Research	Sydney
Austria	University of Vienna Medical School, AKH	Vienna
Belgium	Institute of Tropical Medicine	Antwerp
Belgium	Centre Hospitalier Universitaire Sart-Tilman	Liege
Brazil	Cassiano Antonio de Moraes University Hospital	Boqueirao-Santos
Brazil	Centro de Pesquisa Clinical do Hospital Guilherme	Boqueirao-Santos
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre-RS Cep
Brazil	Hospital dos Servidores do Estado	Rio de Janeiro
Brazil	Hospital Escola Sao Francisco de Asis	Rio de Janeiro	RJ
Brazil	Hospital Universitario Professor Edgard Santos	Salvador-BA
Brazil	Centro de Referencia e Treinamento DST/AIDS	San Paulo
Brazil	Unidade de Pesquisa Clinica	San Paulo
Brazil	Ambulatorio de Imunodeficiencias Secundarias/Der30	Sao Paulo
Brazil	Instituto de Infectologia Emilio Ribas	Sao Paulo	S.p. Cep
Brazil	Universidade Federal De Sao Paulo-Hospital Sao Paulo	Sao Paulo
Canada	University de Sherbrooke	Fleurimont	Quebec
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Hamilton Health Science Centre-McMaster	Hamilton	Ontario
Canada	St. Joseph's Health Care Centre of London	London	Ontario
Canada	St. Josephs Hospital	London	Ontario
Canada	Clinique Medicale L'actuel	Montreal	Quebec
Canada	Montreal Chest Institute/Royal Victoria Hospital	Montreal	Quebec
Canada	Centre hospitalier de l'universite Laval (CHUL)	Sainte-Foy	Quebec
Canada	Recherche Clinique Centre Medical Halles de Saint-	Ste-Foy	Quebec
Canada	The HAVEN Program, HRSRH	Sudbury	Ontario
Canada	Tronto General Hospital	Toronto	Ontario
Canada	Downtown Infectious Disease Clinic	Vancouver	British Columbia
Canada	HIV Care Program, Windsor Regional Hospital	Windsor	Ontario
Estonia	West-Tallinn Central Hospital	Tallinn
France	CHU de la Region Annecienne	Annecy
France	Hopital Pellegrin	Bordeaux
France	Centre Hospitalier Universitaire	Chu-grenoble
France	Hopital Louis Mourier	Colombes
France	Hopital Sainte-Marguerite	Marseille
France	Hopital Pitie Salpetriere	Paris
France	Hopital Saint-Louis	Paris
Germany	Klinik fur Dermatologie, Venerologie, Allergologie	Essen
Germany	Johann Wolfgang Goethe University Hospital	Frankfort
Germany	Klinikum der Ruprecht-Karis-Universitat (U. Hospital)	Heidelberg
Germany	University Hospital Zurich	Zurich Ch-
Ireland	St. James Hospital	Dublin 8
Israel	Ramathibodi Hospital	Tel Aviv
Italy	U.O. Malattie Infettive, H.S.Maria Annunziata	Antella-Firenze
Italy	SOCDU Malattie Infettive Ospedale Civile Asti	Asti
Italy	Instituto de Malattie Infettive e Tropicali	Brescia
Italy	Malattie Infettive Busto	Busto Arsizio (va)
Italy	Universita degli Studi di Modena e Reggio Emilia	Modena
Italy	Clinica Malattie Infettive	Pavia
Italy	I.R.C.C.S."L.Spallanzani"	Rome
Italy	University of Turin	Torino
Italy	Servizio Regionale di Immunologia Clinica e Tipizz	Torrette Di Ancona
Italy	S.S. Giovanni e Paolo Hospital	Venice
Japan	AIDS Medical Center, International Medical Center	Tokyo
Japan	International Medical Center of Japan	Tokyo
Lithuania	Lithuanian AIDS center	Vilnius
Luxembourg	Centre Hospitalier de Luxembourg	Barble
Martinique	C.H.U. Fort-de-France	Fort-de-france
New Zealand	Christchurch Hosp	Christchurch
New Zealand	Wellington Hosp	Wellington
Norway	Ulleval Hospital	Oslo
Peru	Hospital Nacional Edgardo Rebagliati Martins	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen	Lima
Poland	Wroclaw University School of Medicine	Koszarowa Str. 5
Puerto Rico	Instituto A. Z. de Pesquisa e Ensino	Curitiba
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Principe de Asturias	Madrid
Spain	Hospital U. Virgen del Rocio	Sevilla
Spain	Hospital Mutua de Terrassa	Terrassa
Spain	Consorcio Hospital General Universitario de Valencia	Valencia
Switzerland	University Hospital Basel	Basel Ch
Switzerland	Poliklinik fur Infektiologie	Bern
Switzerland	Hopital de la Ville	La Chaux-de-Fonds
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Switzerland	Ospedale Regionale di Lugano	Lugano
Thailand	Sanpatong Hospital	Chiang Mai
Thailand	Bamrasnaradura Institute	Nonthaburi 11000
United Kingdom	Royal Victoria Hospital	Belfast
United Kingdom	Hawthorn House, Birmingham Heartlands NHS Trust	Birmingham
United Kingdom	Southmead Hospital	Bristol
United Kingdom	St. Helier Hospital	Carshalton
United Kingdom	St. Helier Hospital	Carshalton, Surrey
United Kingdom	Essex County Hospital	Essex
United Kingdom	Victoria General Hospital, Q.E. II Health Sciences	Halifax
United Kingdom	Barts and The London, NHS Trust	London
United Kingdom	Central Middlesex Hospital	London
United Kingdom	Chelsea and Westminster Hospital	London
United Kingdom	Homerton University Hospital NHS Foundation Trust	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St. George's Hospital	London
United Kingdom	St. Mary's Hospital	London
United Kingdom	St. Thomas' Hospital	London
United Kingdom	T1 Coleridge Unit, North Middlesex Hospital	London
United Kingdom	The Caldecot Centre, Kings College Hospital NHS Tr	London
United Kingdom	The Mortimer Market Center	London
United Kingdom	The James Cook University Hospital	Middlesbrough
United Kingdom	Pasteur Suite, Ealing Hospital	Middlesex
United Kingdom	Newcastle General Hospital	Newcastle
United Kingdom	John Radcliffe Hospital	Oxford	England
United Kingdom	Dept. of Infection and Tropical Medicine - Royal Hallamshire Hospital	Sheffield
United Kingdom	Watford Sexual Health Center;Watford General Hosp	Watford Wd
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Absolute Care Clinic	Atlanta	Georgia
United States	AID Atlanta/Morehouse Med School Ryan White Cl	Atlanta	Georgia
United States	AIDS Research Consortium of Atlanta (ARCA) Central	Atlanta	Georgia
United States	Cobb-Douglas County Infectious Disease Clinic	Atlanta	Georgia
United States	Dekalb County Health Dept Infectious Disease	Atlanta	Georgia
United States	Dr. Dennis Melton (Private Practice)	Atlanta	Georgia
United States	Dr. Melanie Thompson and Dr. Annette Bernard (Private Practice)	Atlanta	Georgia
United States	Dr. Richard Hudson (Private Practice)	Atlanta	Georgia
United States	HIV Services Clinic/Family Practice Medical Center	Boise	Idaho
United States	Community Research Initiatives of New England	Boston	Massachusetts
United States	Community Research Initiatives/ProACT	Boston	Massachusetts
United States	Bronx Veterans Affairs Medical Center	Bronx	New York
United States	Bronx-Lebanon Hosp Ctr	Bronx	New York
United States	SUNY Downstate Med Ctr	Brooklyn	New York
United States	Cooper Hospital Early Intervention Program	Camden	New Jersey
United States	AIDS Research Alliance - Chicago	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Klein and Slotten Associates / AIDS Research Alliance	Chicago	Illinois
United States	Lakeshore Infectious Disease Associates	Chicago	Illinois
United States	Northside Family Medicine	Chicago	Illinois
United States	Northwestern Memorial Physicians	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Denver CPCRA / Denver Public Hlth	Denver	Colorado
United States	Drs. Lichtenstein & Greenberg	Denver	Colorado
United States	McDowell Healthcare Center	Denver	Colorado
United States	Western Infectious Disease Consultants	Denver	Colorado
United States	Detroit Community Health Connection	Detroit	Michigan
United States	Detroit Receiving	Detroit	Michigan
United States	Henry Ford Hosp	Detroit	Michigan
United States	Mt. Clemens General Hospital	Detroit	Michigan
United States	Providence Hosp- Newland Med Assoc. Inc.	Detroit	Michigan
United States	Wayne State Univ / Medical College of Ohio at Toledo	Detroit	Michigan
United States	Kaiser Permanente-Fremont/Hayward Medical Centers	Fremont	California
United States	McAuley Health Center	Grand Rapids	Michigan
United States	Houston Veterans Administration Med Ctr	Houston	Texas
United States	Montrose Clinic	Houston	Texas
United States	Univ TX Health Science Ctr	Houston	Texas
United States	University Clinical Research Center	Houston	Texas
United States	Michigan State University Infectious Diseases Clinic	Lansing	Michigan
United States	AIDS Healthcare Foundation	Los Angeles	California
United States	Los Angeles Gay and Lesbian Community Service Ctr	Los Angeles	California
United States	Infectious Disease Associates of Virginia	Lynchburg	Virginia
United States	University Of Wisconsin Hospital and Clinics/CORNET, HIV Care Program	Madison	Wisconsin
United States	Miami Veterans Affairs Med Ctr	Miami	Florida
United States	Jersey Shore Med Ctr	Neptune	New Jersey
United States	Veterans Administration Medical Center	New Haven	Connecticut
United States	Yale U / New Haven Med Ctr / AIDS Clinical Trials Unit	New Haven	Connecticut
United States	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana
United States	Our Lady of the Lake Regional Med Ctr	New Orleans	Louisiana
United States	University of Mississippi Medical Center	New Orleans	Louisiana
United States	Grant Houses Health Ctr	New York	New York
United States	HHC MMC Unit #1	New York	New York
United States	HHC Outpatient Clinics	New York	New York
United States	Jacobi Medical Center	New York	New York
United States	Lenox Avenue Health Ctr	New York	New York
United States	Lincoln Medical & Mental Health Center	New York	New York
United States	Metropolitan Hospital Center	New York	New York
United States	Polo Grounds Health Care Ctr	New York	New York
United States	Syndenham Neighborhood Family Care Ctr	New York	New York
United States	Jeffrey Bomser Clinic / NJCR	Newark	New Jersey
United States	New Jersey Community Research Initiative	Newark	New Jersey
United States	NJCRI	Newark	New Jersey
United States	Raritan Bay Med Ctr	Newark	New Jersey
United States	Saint Michael's Med Ctr	Newark	New Jersey
United States	Univ of Oklahoma Health Sciences	Oklahoma City	Oklahoma
United States	Center for Prevention and Treatment of Infections	Pensacola	Florida
United States	Einstein Medical Center	Philadelphia	Pennsylvania
United States	Penn Community Infectious Diseases	Philadelphia	Pennsylvania
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Temple Univ School of Medicine	Philadelphia	Pennsylvania
United States	Legacy Clinic NE	Portland	Oregon
United States	Salem Hospital	Portland	Oregon
United States	The Research & Education Group / Multomah Cnty Hlth Dept	Portland	Oregon
United States	The Research & Education Group / The R & E Grp Office	Portland	Oregon
United States	The Research & Education Grp / Oregon Hlth Sci Univ	Portland	Oregon
United States	The Research and Education Group	Portland	Oregon
United States	The Rsch & Ed Grp / Legacy Cln at Good Samaritan	Portland	Oregon
United States	The Rsch & Ed Grp / Providence Portland Med Ctr	Portland	Oregon
United States	Cross Over Clinic / Div of Infectious Diseases	Richmond	Virginia
United States	McGuire VA / Division of Infectious Diseases	Richmond	Virginia
United States	MCV ID Clinic	Richmond	Virginia
United States	MediCorp, Infectious Disease Associates	Richmond	Virginia
United States	Petersburg Health Care Alliance	Richmond	Virginia
United States	South Richmond Health Ctr	Richmond	Virginia
United States	Vernon J. Harris East End Community Health Care Ct	Richmond	Virginia
United States	Mayo Clinic/CORNET	Rochester	Minnesota
United States	William Beaumont Hospital/CORNET	Royal Oak	Michigan
United States	South Texas Veterans Health Care System	San Antonio	Texas
United States	Community Consortium / UCSF	San Francisco	California
United States	Dr. Shawn Hassler	San Francisco	California
United States	East Bay AIDS Ctr	San Francisco	California
United States	Lawrence Goldyn, MD	San Francisco	California
United States	South Jersey Infectious Disease	Somers Poinnt	New Jersey
United States	Community Research Initiative/ProACT	Springfield	Massachusetts
United States	Southern Illinois University (SIU) School of Medicine	Springfield	Illinois
United States	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida
United States	George Washington Univ	Washington	District of Columbia
United States	Timothy A Price	Washington	District of Columbia
United States	Washington Reg AIDS Prog / Dept of Infect Dis	Washington	District of Columbia
United States	KU Medical School-Wichita, Midtown Clinic	Wichita	Kansas
United States	KU Medical School-Wichita, MPA	Wichita	Kansas
United States	Christiana Care Health Services HIV Program George	Wilmington	Delaware
United States	Wake Forest Univ Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Estonia,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Lithuania,  Luxembourg,  Martinique,  New Zealand,  Norway,  Peru,  Poland,  Puerto Rico,  Spain,  Switzerland,  Thailand,  United Kingdom, 

References & Publications (5)

Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2000 Jan 19;283(3):381-90. Review. — View Citation

Lederman MM, Valdez H. Immune restoration with antiretroviral therapies: implications for clinical management. JAMA. 2000 Jul 12;284(2):223-8. — View Citation

Mocroft A, Katlama C, Johnson AM, Pradier C, Antunes F, Mulcahy F, Chiesi A, Phillips AN, Kirk O, Lundgren JD. AIDS across Europe, 1994-98: the EuroSIDA study. Lancet. 2000 Jul 22;356(9226):291-6. — View Citation

Tebas P, Henry K, Mondy K, Deeks S, Valdez H, Cohen C, Powderly WG. Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+ T cell decline in human immunodeficiency virus-infected patients: implications for intermittent therapeutic strategies. J Infect Dis. 2002 Sep 15;186(6):851-4. Epub 2002 Aug 28. Erratum in: J Infect Dis 2002 Oct 15;186(8):1198. — View Citation

Yerly S, Kaiser L, Perneger TV, Cone RW, Opravil M, Chave JP, Furrer H, Hirschel B, Perrin L. Time of initiation of antiretroviral therapy: impact on HIV-1 viraemia. The Swiss HIV Cohort Study. AIDS. 2000 Feb 18;14(3):243-9. — View Citation

External Links

•   Haga clic aquí para ver información sobre este ensayo clínico en español.