A study in 35 countries that involved 4685 HIV-infected people has ended early because results showed that immediate treatment cut the risk of disease and death in half. The data, revealed today at a teleconference held by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), brings to a close a divisive issue. The United States and many other countries already recommend treating everyone diagnosed with an HIV infection, but guidelines in the United Kingdom and elsewhere call for starting treatment only after immune system damage occurs, in part because of worries about long-term toxicities of the drugs.
As NIAID Director Anthony Fauci explained, evidence suggested that early treatment benefited people but no randomized, controlled clinical trial had ever proven it until now. “These findings clearly demonstrate that starting antiretroviral treatment sooner rather than later is of significant health benefit to the HIV-infected individual,” Fauci said. “These results are certain to impact medical treatment guidelines.” He said the new findings also validate the push to use treatment as a prevention tool, as other studies have shown that HIV-infected people on antiretrovirals (ARVs) are far less likely to transmit the virus to others.
The Strategic Timing of Antiretroviral Treatment (START) trial began in March 2009. At the time, the World Health Organization (WHO) recommended starting ARVs only after a person’s CD4 count had dropped to 200 or less per microliter of blood. CD4s are the white lymphocytes that HIV targets and destroys; normal counts range from 600 to 1200. START enrolled HIV-infected people who had more than 500 CD4s and had never taken ARVs. It randomly assigned half the participants to start treatment immediately, while the other half were offered ARVs after CD4 counts fell to 350 or they developed an AIDS-defining illness. The trial assessed development of the following “events”: AIDS, serious non-AIDS related ailments, and death. START planned to end in December 2016.
A data safety and monitoring board that intermittently reviewed the START data—which were blinded to researchers—notified study leaders this month that after an average of 3 years of observation, the early treatment group had a 53% reduction in risk of suffering an event. Specifically, 41 people who received early treatment had an event versus 86 in the deferred treatment group. No evidence surfaced of increased drug toxicities in the early treatment group. All participants are now being offered treatment, and the trial will continue to follow participants through 2016 as originally planned to assess whether other differences surface because of the delayed treatment. NIAID, the study’s main sponsor, alone has spent $154 million on the trial to date.
Michael Saag, who directs the Center for AIDS Research at the University of Alabama, Birmingham, initially thought START was a waste of money: He was already convinced by both the biology and less rigorously designed, smaller trials that earlier treatment made eminent sense. “I didn’t think the juice was worth the squeeze,” he says. But his initial reaction to these data? “Wow,” Saag says. “I was guessing that this is what they would find, but I frankly didn’t expect we’d see it as early as now. Maybe this effect is even more profound than I was thinking before the trial. And it makes me want to redouble my efforts to identify everyone who is infected and get them on therapy as fast as possible.”
Saag, who sits on the WHO panel that issues international guidelines for HIV treatment, says the new data will likely influence the next revision. “I don’t see any way the WHO can ignore these data,” he says, noting that some poorer countries might still have to prioritize treatment to sicker patients.
The United Kingdom’s HIV treatment guidelines, now being updated, seem certain to change, too, says Ian Williams, an epidemiologist at the University College London who chaired the panel that wrote the previous version. “The START results are clearly very important and impressive,” he says, “and I fully expect will result in a review and change in the guidelines for 2015.”