Simon Collins of HIV i-Base looks at an important and exciting new study of when to start HIV therapy, which needs your help.
The START study (Strategic Timing of Antiretroviral Therapy) looks at when to start treatment and many other aspects of HIV.
Despite twenty-five 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, ageing all interact with HIV.
START has generated a lot of discussion because the US Department of Health and Human Services guidelines1 recently changed the recommended CD4 count for starting HIV therapy from 350 to 500 cells/mm3. But this was based on limited evidence – mainly on expert opinion.
[START] will help us understand how HIV affects our brain, our bones and our heart, whether earlier treatment helps, and how genetics, treatment, ageing all interact with HIV.
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 people before their CD4 count falls below 500 cells/mm3 too. In effect, they are saying we don't need START because we can guess the results. Adding to the debate, the US advocacy group Project Inform issued a public statement in February saying ‘treat everyone above 500’. Subsequently, they have revised this back to under 500.
Others think this issue is far from clear.2 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 still recommend not starting treatment till the CD4 count is below 350 cells/mm3 unless there are other considerations.
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 first HIV-positive test result. But, good as it is, HIV treatment 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.
To take part, you need to have a CD4 count over 500 cells/mm3 without being on treatment, and be currently well. Participants are randomised to either start HIV treatment immediately (at any CD4 count) or wait until their CD4 count drops to around 350 cells/mm3.
Deciding to take part in a clinical study is an individual choice. You have to be happy to use either strategy, because you will be randomised to one or the other. 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 cells/mm3 in any case, and only 10% of people stay above that level for many years without treatment. So finding people to join is a challenge. If you were recently diagnosed, you may need time to come to terms with your diagnosis before starting treatment, but looking into the benefits of early treatment is where some of the most exciting research is currently happening. 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 if they defer 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.
Simon Collins is a member of the Community Advisory Board of the INSIGHT Network, which runs the START trial.
Further information
START sites include the Chelsea and Westminster, Royal Free and St Mary’s hospitals in London, and in Brighton and Leicester. If you are treated at another hospital, you will need to initially visit one of these centres, but travel costs can be reimbursed.
For more details and to contact the researchers see: http://i-base.info/home/start-study/ or contact START@ctu.mrc.ac.uk
i-Base phoneline: 0808 800 6013.