The START study (Strategic
Timing of Antiretroviral Therapy) looks at when to start treatment and many
other aspects of HIV.
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
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.
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
our heart, whether earlier treatment helps, and how genetics, treatment,
all interact with HIV.
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.
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.
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.
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
Simon Collins is a member of the Community
Advisory Board of the INSIGHT Network, which runs the START trial.
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
details and to contact the researchers see: http://i-base.info/home/start-study/
or contact START@ctu.mrc.ac.uk
0808 800 6013.