For a long while, the most pressing question in the world of HIV has been: when is the best time to start antiretroviral treatment? As David Menadue reports, it seems we now have a decisive answer.
Opinion has long been divided over when to start treatment for HIV. On the one side: as soon as possible; on the other: best to wait. Now there can be no doubt. The announcement of the findings of the START study in May this year provides clear evidence of the value of starting treatment while T-cells are still high rather than waiting until they drop to 350 or below and the immune system is weakened.
Up until now, global treatment guidelines have skewed conservative, holding back the use of antiretroviral treatment (ART) until there were signs that an individual’s HIV was progressing. Professor Sean Emery, START coordinator from the Kirby Institute in Sydney, said there should now be no hesitation in advising treatment upon diagnosis. “I don't think that clinicians should feel any discomfort recommending people with HIV start treatment as early as they like,” said Emery. “There is no clinical reason to wait until you get to a certain CD4 count to treat anymore.”
The study’s findings validate the changes made last year to Australia’s treatment guidelines allowing people with HIV universal access to ART irrespective of CD4 count (the US Department of Health and Human Services recommends the same). And, in light of the START findings, the World Health Organisation has ammended its treatment guidelines recommending ART as soon as possible after diagnosis.
Primarily funded by the US National Institutes of Health, START (Strategic Timing on Anti-Retroviral Treatment) was set up in 2008 to answer a question that needed a definitive answer: is there a real clinical advantage to starting treatment earlier rather than later? More than 4,500 HIV-positive people helped provide the answer in a study spread over 35 countries — including Australia.
Professor Emery found it difficult recruiting Australians at first, as many were reluctant to commit to ART until absolutely necessary. Attitudes changed markedly after two landmark studies. "In 2011 with the HTPN 052 study, and then the PARTNER study in 2014, the real benefit of being on treatment and getting an undetectable viral load (and hence reducing your risk of transmitting the virus to partners) became clearer,” said Emery. “HIV-positive people started to see the benefits of being uninfectious to others and that changed some attitudes to treatment."
START participants had never taken antiretroviral treatment before and had to have a CD4 count of at least 500. They had to agree to be randomised into the two arms: immediate treatment or deferred treatment (waiting until CD4 counts dropped to 350 or an AIDS-defining illness had developed). In May, the study generated global headlines when it was stopped 18 months ahead of schedule because the clinical benefits of treating earlier were overwhelming: among those who were treated immediately, the risk of illness or death was cut by half.
The Data Safety Monitoring Board found there were 41 AIDS or serious non-AIDS events or death in the treatment arm, compared with 86 events in the deferred arm — a difference of 53 percent. Findings were the same for low-, middle- and high-income countries. “As a result of this trial we now know that treatment at all stages of the disease extends survival and prevents serious complications in people with HIV,” said Emery.
With 12 million people on treatment and 30 million infected worldwide, providing ART for everyone with HIV is going to come at a cost. Emery acknowledges there will be financial implications — especially in developing countries. “While efficiencies can be made in how medicines are distributed and drug companies can be lobbied to reduce prices, other innovations need to be looked at,” said Emery, “like reducing the dosages of some drugs — and hence their cost — as we currently think some people are getting higher doses of some drugs than they need for therapeutic benefit."
As for Australia, at AIDS 2014 in Melbourne, every health minister (federal and state) signed up to a Legacy Statement that aims to end HIV by 2020. This can only be achieved through increased testing; increased access to treatment; and increased numbers of those on treatment reaching viral suppression.
Informed conversations within the positive community, including GPs, about the value of early treatment will also be needed if we’re to get anywhere near ending HIV in Australia. Finally, the START trial now provides clinicians and positive people alike the evidence that they have long needed: that treating HIV as close to diagnosis is the way to go.