START… and why the time is now?
Simon Collins of HIV i-Base looks at an important and exciting new study, which needs your help.
The START study (Strategic Timing of Antiretroviral Therapy) is exploring when to start treatment and many other aspects of HIV.
Why is START so important?
Despite 25 years of research, there has never been a randomised study looking at the best time to start treatment. START is important because it is randomised. This is not just a technical point. It means that the results will be accurate and real. Nearly all the current evidence for starting treatment, is based on studies where other factors can affect the results, and which do not measure risks.
START will help show the differences between starting at 350, 500, 900 or at even higher CD4 counts? It will help us understand how HIV affects our brain, our bones and our heart, whether earlier treatment helps, and how genetics, treatment and ageing all interact with HIV.
Is this controversial?
START has generated a lot of discussion because the US Department of Health and Human Services guidelines recently changed the recommended CD4 count for starting HIV therapy from 350 to 500 cells/mm3. But this was based on limited evidence – mainly graded as expert opinion.
Their reasons were that we now have safer and more tolerable drugs, that untreated HIV causes other health complications, and that having more people with undetectable viral loads will reduce transmission. But defining exactly when the benefits of treatment outweigh the risks is not clear.
Some of the US experts recommended treating everyone with CD4 counts above 500 cells/mm3 too. They were not saying ‘we don’t need the START study’ but that rather, while waiting for results, they prefer to recommend treatment.
Others think this issue is far from clear. A community statement to the US guidelines panel signed by over 150 organisations, including i-Base and NAM, supported the importance of START in order to study what happens if people start treatment with CD4 counts between 350 and 500 cells/mm3. Guidelines in the UK and European countries remain at 350.
Why not just treat everyone anyway?
Why not just treat everyone anyway? If HIV treatment had no side-effects and was robust, effective, cheap, not prone to resistance or needing high adherence, everyone could start treatment with their HIV-positive test result. But, good as it is, it doesn’t score highly on all of these factors.
There is good evidence for treating once your CD4 count has dropped below 200 cells/mm3, and for treating everyone below 350 cells/mm3 if there is access to modern treatment. But current research suggests only small absolute benefits at higher CD4 counts, when there is only a small chance of any HIV-related health complication. Opinions may be strong both for and against treatment above 350 cells/mm3, but the evidence is weak.
Who can take part and what is involved?
To take part in START you need to have a CD4 count over 500 without being on treatment, and be currently well. Participants are randomised to either start HIV treatment (at any CD4 count) or wait until their CD4 count drops to around 350.
Deciding on any study is an individual choice. You have to be happy to use either strategy. Currently while most doctors might personally guess one option might be better, they generally agree that the evidence for either position is limited.
Only about 10% of people are diagnosed with CD4 counts over 500 and only 10% of people stay above 500 for many years without treatment. So finding people to join is a challenge. If you were recently diagnosed, you will need time to come to terms with your diagnosis, but early treatment is some of the most exciting current research. If you have been controlling HIV well for several years without treatment, there is increasing evidence suggesting that even long-term slow progressors could be at risk from deferring treatment for many years.
If you choose to take part, as well as getting great care and the chance for monitoring not generally available in clinics, you can contribute safely to an important research project.
START sites include the Chelsea and Westminster, Royal Free and St Marys hospitals in London, and Brighton and Leicester. If you are treated at another hospital, you can register through your current clinic. This may require a visit to one of these centres, but travel costs can be reimbursed.
Study details: http://clinicaltrials.gov/ct2/show/NCT00867048
Non-technical information: http://i-base.info/home/start-study/
Community support statement: http://i-base.info/home/community-statement-supporting-start-trial/
For further details please contact: START@ctu.mrc.ac.uk
i-Base phoneline: 0808 800 6013.