START is one of the most important HIV studies from the last ten years.
It was designed to look at the benefits and risks of early HIV treatment (ART).
In May 2015, results showed that ART has important benefits even for people with a high CD4 count.
As a result, leading treatment guidelines were quickly changed. This includes UK guidelines (BHIVA) and international guidelines (WHO). Previous guidelines said it was okay to wait until your CD4 counts dropped to a lower level.
Who was in the study
START included more than 4600 HIV positive people from 35 countries.
Everyone entered the study with a CD4 counts above 500.
Half of participants started ART straight away and half waited until their CD4 count reached 350.
Early ART more than halved the risk of a serious illness.
Even though the actual risk was low – most people did well in both groups – the difference between the two groups was highly significant.
The benefit of treatment was seen for all important sub groups. For example in older and younger people (above/below 35), in men and women, in people living in both high- and low-income countries, and in people with and without risk for other important illnesses.
START showed that early ART was also safe and effective.
About 98% of people who started treatment had an undetectable viral load at the end of their first year of treatment.
START stands for Strategic Timing of AntiRetroviral Treatment.
- Q&A on the START results
- Detailed report of START results from the 2015 AIDS conference
- Information on START at clinicaltrials.gov.
- Information on START at the INSIGHT website.
This study enrolled 4685 people from over 230 clinics in 36 countries.
The study was due to present results in 2017 after including at least 4.5 years of follow-up on all participants.
In May 2015, 18 months early, results showed that earlier treatment was better. All participants were then offered immediate treatment.
The study is still continuing to follow all participants until at least the end of 2016.
The study was for people who had not yet used HIV drugs (called ‘treatment-naive’) and who have CD4 counts higher than 500 cells/mm3. Participants were randomised (like tossing a coin) to either early treatment (immediate group) or to wait until their CD4 count reached 350 cells/mm3 (deferred group).
The rationale for earlier treatment above 500 was based on:
- Greater efficacy and tolerability of current first-line drugs: because treatment is more effective and has fewer side effects this makes it easier to use. There is less need to put off taking treatment because of negative risks from treatment.
- Increasing evidence data from cohort studies (large databases) that show an higher relative risk of rare but life threatening diseases in patients at CD4 counts above 350 cells/mL in people not on treatment. Note that the absolute risks are still low when on treatment or not.
The rationale for waiting until 350 was based on:
- Evidence from randomised trials showed a benefit of starting at 350 compared to waiting until 200 or lower.
- During the study, 350 was the cut-off in UK treatment guidelines.
- That the absolute risk of other complications is generally very low when CD4 counts are above 350.
- That 95% of people starting treatment at 350 will still get a CD4 increase to over 500 (called a ‘normal’ CD4 count).
The study included a broad range of important sub-studies including: genomics, neurology, cardiovascular and lung disease and bone health.
Finding a benefit from earlier treatment has the potential to narrow the gap in life expectancy that still exists between HIV negative people and HIV positive people. This will be balanced against potential risks of side effects, drug resistance and a negative impact on quality of life, in the context of the prospect of long-term treatment.
Many HIV positive people may think there is little difference between being on treatment for 30 years, or 32 years (starting slightly earlier), for the chance of higher and more durable CD4 responses and a reduced risk of complications that are currently rare but which may increase as we age.
Current status: Ongoing: all participants are now offered ART and follow up continues until the end of 2016.
Ongoing data and safety reports (open reports about enrolment and safety).
For further details please contact: START@ctu.mrc.ac.uk
Links to articles about the early study
START for people who are recently diagnosed. (i-Base leaflet)
START for people who long-term slow progressors. (i-Base leaflet)
Community statement on START study – May 2010
Article on START in BASELINE magazine – June 2010
Web blog on START by Dr Joseph Sonnabend – April 2010
“If knowledge is power, a demand to complete the START trial is the embodiment of the self empowerment of HIV positive individuals. The very antithesis of self empowerment is to allow researchers to persuade us with evidence of inferior quality, such as their personal opinions, presented as if they represented a consensus, or with the results of embarrassingly uninterpretable studies such as NA-ACCORD, so often used to justify earlier starts to treatment.”