'25 at 25': Saving lives with early HIV treatment
22 Jan 2024
During the 25th anniversary year of the MRC Clinical Trials Unit at UCL, we celebrate the fact that millions of people with HIV are now living longer, healthier lives thanks to our research. This article is part of a series highlighting 25 major achievements from the 25 years since the MRC CTU at UCL was formed. It focuses on three pivotal trials which transformed HIV treatment guidelines globally, helping millions avoid serious illness or death due to HIV.
HIV attacks the immune system, putting people at risk of serious illnesses and infections. Luckily, antiretroviral therapy (ART) is very effective at treating HIV. But these drugs often come with side-effects. It was previously unknown if people living with HIV in the early stages of the disease would benefit from starting treatment early, or if they should wait until their immune system began to weaken. It was also thought to be safe to pause treatment once their immune system had recovered.
SMART
Between 2002 and 2006, 5,472 people living with HIV from 33 countries around the world agreed to take part in the SMART clinical trial. Researchers compared one group who took ART continuously with another group who only took treatment when their immune system showed signs of weakness.
SMART found that interrupting treatment in adults more than doubled the risk of HIV getting worse, compared with staying on treatment continuously. These results confirmed that it was unsafe to pause treatment without good reason, and prompted further research into the best time to start treatment in people diagnosed with HIV.
START
The START trial followed in 2009, involving 4,685 adults living with HIV from 35 countries, all at an early stage of the infection with relatively healthy immune systems. Half of the participants began taking ART immediately, while the other half started treatment only when their immune cell count dropped.
START found that starting ART straight away more than halved the rate of serious illnesses and deaths. The results sent a clear message: everyone diagnosed with HIV should begin treatment immediately, whatever the state of their immune system.
Over the past 25 years, many of our studies have led to changes in healthcare policy and practice, but few have had quite as swift an impact as the START trial. Following the release of the START results in 2015, the World Health Organization (WHO) announced that it would update its HIV treatment recommendations at the very same conference.
Other guideline developers soon followed suit, including the British HIV Association. WHO data from 2016 showed that the proportion of low- and middle-income countries applying a ‘treat all’ policy for ART has doubled. According to UNAIDS, in 2019 25.4 million people were accessing ART, up from 6.4 million in 2009. Meanwhile in the UK, HIV incidence among men who have sex with men has plummeted by 71%, thanks in part to ART becoming available immediately after diagnosis.
CHER
While SMART and START focused on adults, the landmark CHER trial offered new hope for babies who acquire HIV from their mother during pregnancy, birth or breastfeeding. When the trial first opened in 2005, a third of infants with HIV died before their first birthday and half died before the age of two. At that time, infants did not usually start treatment until they showed signs of immune system damage.
CHER tested whether it was better to start babies on treatment immediately (before 12 weeks of age) for one or two years before taking a break, or to wait until they developed symptoms or a weakened immune system, then continuing treatment for life. The results revealed that treating infants early saves lives. Those who started treatment straight away were more likely to survive longer and with no symptoms than those who started treatment later. This benefit continued over five years of follow-up.
The CHER trial also had a rapid impact on healthcare policy. Before the results were even published, it led to a change in WHO and other guidelines across the world in 2008 to recommend treating infants as soon as their HIV status is known.
A third of those who had an early course of ART were still well enough not to need treatment three years later. But one particular CHER participant stunned the medical community when, after receiving just 40 weeks of ART starting at nine weeks old, the virus was still suppressed without drugs well over a decade later. Researchers detected a reservoir of virus inside a very small proportion of immune cells, but otherwise found no evidence of HIV infection. This was the first reported child to have undetectable levels of HIV in the blood for so long.
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