People expected the results to be good. But they never expected them to be this good.
An IAS 2015 session entirely devoted to the START study -- the HIV research community's most comprehensive effort yet to determine the value of starting a patient immediately on antiretroviral therapy upon a positive HIV diagnosis, regardless of CD4 count -- was given top billing by the conference organizers. It took place at 11 a.m. on the first full day of the conference, and although it technically competed with six other sessions on the schedule, the layout of the online conference program ensured that the START session would be seen first by anyone browsing the morning's options.
Fortunately, the session didn't disappoint.
It began with a sweeping, 30-minute presentation in which nearly four dozen slides were presented -- and we saw hints of at least a dozen more "backup" slides kept in the wings in case of emergency, or perhaps a particularly challenging follow-up question from the packed audience of more than 1,000 conference delegates. During those 30 minutes, we learned that:
- At study initiation, the average CD4 count was almost identical between people who were randomized to start HIV treatment immediately and those who deferred.
- Those numbers quickly separated. After as many as 60 months of follow-up, the immediate-therapy arm had an estimated mean CD4 count 194 cells/mm3 higher than the deferred-therapy arm.
- People in the immediate-therapy arm had a 57% reduction in their risk of experiencing a serious AIDS-related event, serious non-AIDS event or death relative to people in the deferred-therapy arm.
- Fifty serious AIDS events (mostly tuberculosis, lymphoma and Kaposi's sarcoma) occurred within the deferred-therapy arm, compared to 14 among the immediate-therapy arm.
- Forty-seven serious non-AIDS events (usually a cancer diagnosis, onset of cardiovascular disease or death from some other cause) occurred within the deferred-therapy arm, compared to 29 among the immediate-therapy arm.
- Twelve people died in the immediate-therapy arm; 21 people died in the deferred-therapy arm.
- The benefits of immediate therapy were similar regardless of baseline CD4 count or HIV viral load.
- The benefits of immediate therapy were similar whether people were above or below the age of 35.
- The benefits of immediate therapy were similar whether people were male or female.
- The benefits of immediate therapy were similar whether people were black, white or another race.
- The benefits of immediate therapy were similar whether people were living in a high-income region or not.
- The benefits of immediate therapy were similar whether people were cigarette smokers or not, and regardless of their Framingham cardiovascular risk score.
- That said, cardiovascular events in particular occurred at a nearly identical rate regardless of study arm.
Taken as a whole, the results -- which you can read about in considerably more detail in Simon Collins' recap, or by reading the published results for free in the New England Journal of Medicine -- are stunning. Not because they show early HIV treatment works; that was fully expected. Because they show early HIV treatment works so demonstrably well in almost every conceivable way, across ages, sexes, races and risk groups.
During the 90-minute session, one individual did most of the talking. That was Jens Lundgren, M.D., perennial HIV research luminary; you may remember him from another landmark study, D:A:D, which quantified the relative toxicity risks of long-term antiretroviral use. He guided us through the study construction and its results, which ended with about as firm a conclusion as we're ever likely to see in a presentation by a researcher, where findings are typically accompanied by a litany of caveats and limitations. "Combination antiretroviral therapy should be recommended for all HIV-positive persons, regardless of CD4 count," he said. Period. End of story.
When he was done, Lundgren yielded the stage to an all-star lineup of half a dozen high-profile HIV researchers and prominent clinicians, all of whom had spent the past 35 minutes quietly sitting at tables to either side of him as he spoke.
Expert Reaction: Silver Linings, With a Hint of Cloud
Onstage research analysis: This kind of thing doesn't happen very often at HIV science meetings. Normally, even when study findings are considered to be major, a single researcher stands at a podium for 10 or 15 minutes, takes the audience on a guided PowerPoint tour of charts, graphs and acknowledgements, receives a round of polite (perhaps even slightly energetic!) applause, and fields a few questions. Then she or he demurely sits down, and the session moves on to its next topic. Any ripples created by the dropping of a single presentation into the HIV research pond are left for the community to discern. There is no special panel of experts sitting on stage to discuss its importance.
For START, however, the conference organizers wanted to make sure the impact of the findings was as direct and profound as possible.
Kenly Sikwese, the coordinator of the African Community Advisory Board and a member of the board of UNITAID, called today "a very special day for many of us." He recalled a workshop, just two years ago, in which there was an emotional debate over whether there was value to initiating early HIV treatment. He echoed a theme set by speakers at IAS 2015's opening session the night before: That the START findings not only prove the value of early HIV treatment, but the urgency of it.
Ambassador Deborah Birx, the U.S. Global AIDS Coordinator, amplified that message: "We have 20 million people awaiting treatment" worldwide, she said. "When you start doing the multiplications, it's hundreds of thousands of events -- hundreds of thousands of events -- that could be prevented, month after month, day after day." As soon as the results came out, she said, she cabled "all of our ambassadors" about the findings for what she termed "health diplomacy" -- an effort to pressure countries to translate these results into real programs. "We have to plan now," she said. "All of us have a moral obligation now, because the events are ticking."
Gottfried Hirnschall, M.D., the director of the HIV department of the World Health Organization (WHO), said that the biggest implication of the START study's conclusive findings on the importance of universal treatment access is that "now we really have to do it." Although he offered that the WHO HIV treatment guidelines -- followed by many countries around the world, particularly resource-poor nations where the bulk of the global viral burden lies -- evolved in a slow, deliberate, systematic fashion, he also strongly suggested that an update to the guidelines later in 2015 "would move toward recommending antiretroviral treatment for all people with HIV, of all ages." Might not get all the way there, but would "move toward" it.
Salim Abdool Karim, M.D., Ph.D., the director of the Centre for the AIDS Programme of Research in South Africa, who is perhaps best known as the researcher who presented to the world the first tantalizing evidence that there may be an effective female-controlled form of HIV prevention (research that was overshadowed by subsequent developments with pre-exposure prophylaxis), pointed specifically to the question of adverse events and the relative risks of taking HIV medications. START, he said, "provides a strong and compelling argument to those naysayers that have continually argued we shouldn't put patients early on treatment because of the effects of therapy. So to me, it lays that issue to rest."
If there was any dark spot to find within the vast silver lining that this conference session sought to cast across the HIV treatment firmament, it was elucidated by the final two post-game analysis experts to speak, Zunyou Wu, M.D., Ph.D., and Kate Thomson. Wu, the director of China's National Center for AIDS/STD Control and Prevention, cautioned against any presumption that dominoes will quickly fall in the effort to broadly expand HIV treatment access. The issue was not necessarily one of policy or funding obstacles, he suggested; it was more one of persistent stigma and ignorance. "In the reality, not many doctors really support this early treatment -- even [if] you have scientific evidence," he said. "Not many people who [are] infected will want to take ART early."
Kate Thomson, a long-term HIV survivor who heads the Critical Enablers and Civil Society Hub of the Global Fund, picked up that concept. Although she said this represented a "defining moment" in the history of the fight against HIV/AIDS, the question was how to turn this science into real change on the ground. Certainly, the logistics will be extremely complex -- but so will the effort to change people's minds. "We're gonna need to change the thinking at community level, because this is a real paradigm change," she said. "Treatment, for many of us, for many years, has mainly been focused in people's minds on those who are already sick. Treating people with no symptoms, if you feel well, will be different -- especially when taking ART may be the first time that they feel unwell, through initial side effects."
Thomson, like many others on stage, also pointed to the need for more HIV testing and linkage to care, as outlined in the UNAIDS 90-90-90 targets. But despite the challenges ahead, she -- again, like many others on stage, and many more throughout the conference -- nonetheless exhorted everyone present to imagine, within just a few years, another panel of experts sitting on the stage of a major HIV conference, this time to inform attendees that HIV was no longer a public health threat.
"Let's all dream that dream," she said.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.