Simon Collins, HIV i-Base
On 27 May 2015, at least 18 months earlier than anyone expected, one of the largest ongoing HIV studies announced early results.
The news was given at a high-level press conference in Washington by Dr Anthony Fauci, head of the US National Institute for Allergy and Immune Diseases (NIAID).
Together with the surprise timing, the results themselves were also not what anyone predicted.
The press release was right to say that the results will change HIV treatment guidelines across the world.
What is the study and the key results
This is an international study called Strategic Timing of AntiRetroviral Treatment (START).
Since 2009, it has been studying the impact of early treatment. This involved either starting when their CD4 count was still above 500 or waiting until it reached 350.
The excitement over the results is not just for doctors and researchers. The results are important for HIV positive people.
Main findings include:
- HIV treatment was safe for people starting HIV meds with a high CD4 count. Many people in START had a CD4 count above 800.
- Early treatment led to fewer serious AIDS-related illnesses, even at high CD4 counts.
- The biggest impact from early treatment was expected to be on illnesses like heart, liver and kidney disease and some non-AIDS cancers. The opposite was true. This is big news.
- The results were similar in in both low- and high-income countries. This should result in making HIV treatment more available in all countries.
Everyone in START will now have the chance to start early treatment, even at very high CD4 counts.
Why are the results so exciting?
The START results are important is for at least three related reasons.
Firstly, they will change the way HIV reatment is prescribed. For the last 30 years, most decisions to treat HIV has depended on the CD4 count dropping to a certain level. START should mean that the next step after an HIV diagnosis will now be treatment.
Secondly, the results show that benefits of treatment and prevention overlap. Other studies have proven that treatment dramatically reduces HIV transmission. Now people using treatment as prevention (TasP) will know there are direct benefits for their own health too.
Thirdly, this will make it easier to design programmes to end the AIDS epidemic.
Who was enrolled in START?
Any research study is really a story about real people and the HIV positive volunteers in START were interesting and diverse.
People were enrolled from 35 countries: from Europe, North and South America, Africa, Asia and Australia.
About half were gay men and more than 1 in 4 were women. The average age was 36 but ranged from 18 to 81.
Everyone started with a CD4 count above 500 and the study followed people for an average of 3 years.
However, just as in the general population, people had other health issues.
- One third were current smokers.
- Half had one or more risks for heart disease.
- One in five had complications of high blood pressure.
The study included people with diabetes, hepatitis coinfection, people with alcohol and drug issues, and psychological problems including depression.
How much better was early treatment?
Because of the high CD4 counts, the risk of HIV illnesses was expected to be very low. This was shown in the overall results.
Less than 3% of people had serious complications. The number of these cases was lower than expected in both groups. However, the differences between the two groups was big enough to change the study. Early treatment will now be offered to everyone in the study.
People in the early treatment group had roughly half the risk of a serious HIV related illness (reduced by 53%). The comparison with people starting later was very significant.
The early group had fewer cases of two HIV-related cancers – Kaposi’s Sarcoma (KS) and non-Hodgkin lymphoma (NHL), and fewer cases of tuberculosis (TB).
More details about these results are in the Q&A below.
Were there risks from earlier treatment?
Because only early results are released, we need to wait for details about specific risks.
We don’t know how many people became undetectable on treatment. We don’t have specific information about side effects. We don’t know whether drug resistance will be an important caution.
We also don’t know about how treatment affects overall quality of life.
As well as the main study, several sub-studies looked at these issues.
In general though, the lower number of very serious illnesses is likely to still mean that the benefits of early treatment outweigh the risks.
What happens now?
The study is going to continue to follow everyone in the study.
- People who are already on treatment will continue with the same treatment and monitoring.
- People in START who are not yet on treatment will now be offered treatment.
Over the next two months, the researchers will collect outstanding information. This will go into a more detailed analysis.
These results are likely to be presented at the International AIDS Conference being held in Vancouver in July 2015. The results from the sub-studies will also be presented.
START has created a cohort of people that might have potential advantages for long-term follow-up that will never again be possible.
When the study eventually closes, there is a commitment to continue providing treatment for at least six months. This is so the health providers in each country take on this responsibility.
The START study was rooted in a community demand for good evidence.
When there is not good evidence we have to rely on expert opinion. The lack of evidence often meant that guidelines in the past did not always get it right. The early years of HIV treatment included many examples of guideline changes after evidence became available.
The START study is therefore an important achievement for asking for evidence over opinion. Good evidence is an essential step towards getting good care. This might even be more important that the overall finding that supports use of ART at any CD4 count: it is the level of confidence that can be relied on when discussing the important question of when to start treatment.
With over 12 million people on HIV treatment globally, the decision for the best time to start treatment was too important not to want the best quality evidence. This involved a randomised study. It also involved several thousand people volunteering to be part of the study.
A lot has happened since the first person enrolled. Early discussions about the study in 2009 included a worry that people might never agree to start at such high CD4 counts.
It was also unsettling that not everyone supported the study, when all we were really asking for was good evidence. It was even unsettling to see how passionately some people objected to START.
The results show exactly why the study was needed. Nobody thought that early treatment would reduce AIDS events at very high CD4 counts.
It is significant that most people who joined the study, stayed in the study. More people stayed connected to for their care than is commonly reported even for a study of a new drug treatment.
So before going on to the many debates about the results, it is good to first pause for a moment to acknowledge the research team that drove this study and the HIV positive people without which none of this would have been possible.
i-Base Q&A on the START results.
The press release and NIAID press release and NIAID Q&A are online.
The open DSMB reports are posted to the START website.
Technical report on the START study results in the i-Base HIV Treatment Bulletin.
Community web sites and newsletters are likely to cover this widely.