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A Comparison of Two Ways to Manage Anti-HIV Treatment (The SMART Study)
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00027352

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.

HIV Infections

MedlinePlus related topics: AIDS AIDS Medicines
U.S. FDA Resources
Study Type: Observational
Study Design: Prospective
Official Title: A Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 6000
Detailed 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.


Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00027352

  Show 225 Study Locations
Sponsors and Collaborators
Study Chair: Wafaa El-Sadr, MD, MPH Harlem AIDS Treatment Group, Harlem Hospital Center
Study Chair: James Neaton, PhD CPCRA Statistcal and Data Management Center / CCBR
  More Information

Click here for the NIH News press release, "International HIV/AIDS Trial Finds Continuous Antiretroviral Therapy Superior to Episodic Therapy," 01/18/06  This link exits the ClinicalTrials.gov site
Haga clic aquí para ver información sobre este ensayo clínico en español.  This link exits the ClinicalTrials.gov site

Publications indexed to this study:
Mocroft A, Wyatt C, Szczech L, Neuhaus J, El-Sadr W, Tracy R, Kuller L, Shlipak M, Angus B, Klinker H, Ross M; INSIGHT SMART Study Group. Interruption of antiretroviral therapy is associated with increased plasma cystatin C. AIDS. 2009 Jan 2;23(1):71-82.
Fox Z, Phillips A, Cohen C, Neuhaus J, Baxter J, Emery S, Hirschel B, Hullsiek KH, Stephan C, Lundgren J; SMART Study Group. Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen. AIDS. 2008 Nov 12;22(17):2279-89.
Tedaldi E, Peters L, Neuhaus J, Puoti M, Rockstroh J, Klein MB, Dore GJ, Mocroft A, Soriano V, Clotet B, Lundgren JD; SMART Study Group and International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). Opportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the strategic management of antiretroviral therapy (SMART) study. Clin Infect Dis. 2008 Dec 1;47(11):1468-75.
Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Neuhaus J, Nixon D, Paton NI, Neaton JD; INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008 Oct 21;5(10):e203.
SMART Study Group; El-Sadr WM, Grund B, Neuhaus J, Babiker A, Cohen CJ, Darbyshire J, Emery S, Lundgren JD, Phillips A, Neaton JD. Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial. Ann Intern Med. 2008 Sep 2;149(5):289-99.
Strategies for Management of Anti-Retroviral Therapy/INSIGHT; DAD Study Groups. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients. AIDS. 2008 Sep 12;22(14):F17-24.
Gordin FM, Roediger MP, Girard PM, Lundgren JD, Miro JM, Palfreeman A, Rodriguez-Barradas MC, Wolff MJ, Easterbrook PJ, Clezy K, Slater LN. Pneumonia in HIV-infected persons: increased risk with cigarette smoking and treatment interruption. Am J Respir Crit Care Med. 2008 Sep 15;178(6):630-6. Epub 2008 Jul 10.
Phillips AN, Carr A, Neuhaus J, Visnegarwala F, Prineas R, Burman WJ, Williams I, Drummond F, Duprez D, Belloso WH, Goebel FD, Grund B, Hatzakis A, Vera J, Lundgren JD. Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther. 2008;13(2):177-87.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up. J Infect Dis. 2008 Apr 15;197(8):1145-55.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008 Apr 15;197(8):1133-44.
Carr A, Grund B, Neuhaus J, El-Sadr WM, Grandits G, Gibert C, Prineas RJ; SMART Study Investigators. Asymptomatic myocardial ischaemia in HIV-infected adults. AIDS. 2008 Jan 11;22(2):257-67.
Burman WJ, Grund B, Roediger MP, Friedland G, Darbyshire J, Wu AW; SMART Study Group. The impact of episodic CD4 cell count-guided antiretroviral therapy on quality of life. J Acquir Immune Defic Syndr. 2008 Feb 1;47(2):185-93.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group; El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fatkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006 Nov 30;355(22):2283-96.

Study ID Numbers: CPCRA 065, SMART
Study First Received: December 4, 2001
Last Updated: December 12, 2008
ClinicalTrials.gov Identifier: NCT00027352  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Physician's Practice Patterns
Anti-HIV Agents

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on January 30, 2009