A Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)
A Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)
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.
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.
Note: Enrollment into this trial was halted 01/11/06.
Inclusion Criteria:
Exclusion Criteria:
New Haven, Connecticut 065102483, United States
Washington D.C., District of Columbia 20422, United States
Atlanta, Georgia 30308, United States
Somers Poinnt, New Jersey 08244, United States
Madison, Wisconsin 53792, United States
Burwood Nsw, 2134, Australia
Prahan, Australia
Prahan, Australia
Boqueirao-Santos, 11045-904, Brazil
Boqueirao-Santos, 11045-904, Brazil
Porto Alegre-RS Cep, 90035, Brazil
Salvador-BA, 110-160, Brazil
Ste-Foy, Quebec G1V 4P9, Canada
Chu-grenoble, France
Zurich Ch-, 8091, Germany
Antella-Firenze, 50011, Italy
Torrette Di Ancona, 71-60020, Italy
Barble, L-1210, Luxembourg
Koszarowa Str. 5, Poland
Curitiba, 80430-040, Puerto Rico
Basel Ch, 4031, Switzerland
Essex, CO3 3NB, United Kingdom
Sheffield, S10 2JF, United Kingdom
Watford Wd, 18 0HB, United Kingdom