A large, simple trial comparing two strategies for management of anti-retroviral therapy

A question asked by many people is ‘Do people who start treatment for HIV infection need to stay on it?’

What was this study about?

The purpose of the trial was to compare the consequences of two different ways of giving HIV drugs. Many doctors treat people living with HIV with daily drugs in order to keep the amount of virus in their blood (viral load) as low as possible. We know that this approach to using anti-HIV drugs is very effective in helping people live longer without serious diseases. But we did not know if this meant that they had to stay on continuous treatment after their immune systems had recovered.

It was thought that it would be safe to interrupt treatment in patients who were well, thus sparing them the side effects and problems of taking their drugs on a daily basis. As long as they were carefully monitored and restarted treatment if their immune systems showed signs of weakening.

This appeared to be a safe strategy, as research suggested that patients may be able to wait to use anti-HIV drugs, because the risk of getting sick appeared low while CD4 counts are higher than 250 cells. CD4 cells are the cells that are affected by HIV; these cells are important in maintaining a healthy immune system. Most information used to guide doctors and patients about the treatment of HIV disease comes from different types of studies that were carried out over a short period of time.

The SMART trial compared patients who took continuous treatment with those who took treatment only when their immune system showed signs of weakening. In the trial, patients were randomised to one of two ways of using anti-HIV drugs:

  1. In the first group, doctors waited to use anti-HIV drugs while a patient’s chance of getting sick from HIV infection is low, based on his/her CD4 cell count (the WAIT group)
  2. Patients in the second group were given anti-HIV drugs early on to keep their viral load (amount of virus in the blood) as low as possible (the GO group)

What difference did this study make?

The results from information collected up until January 2006 showed that interrupting treatment at a predetermined level of CD4 cells more than doubles the risk of HIV getting worse, compared with taking treatment all the time. All patients who were off treatment were asked to restart as soon as this result became known. Researchers are now analyzing all of the information collected up to July 2007 to see if the disadvantages of treatment interruption get less over time.

This study shows that it is unsafe to interrupt treatment in patients with HIV without a good reason. An unexpected result was that the risks from side effects from the drugs, used to treat HIV were less than expected and appeared less than the risk of disease caused by HIV if the treatment was not given.

These results have prompted further research on the best time to start treatment for patients who are HIV positive.

Type of study

Randomised trial

Contact details

Who funded the study?

The National Institutes of Health (NIH) in Washington, USA.

When did it take place?

The SMART trial opened to recruitment in January 2002 and closed in January 2006. Researchers and healthcare workers followed the patients until July 2007.

Who was included?

5472 people who are living with HIV were recruited from 33 countries and 318 hospitals and clinics around the world.