The potential benefits of early treatment, as spelled out by the data reported thus far, are encouraging to say the least. But the only way to know these benefits are what they seem to be is to conduct a scientific study. In fact, a massive study exploring the potential health benefits and risks of early HIV therapy is currently under way. It’s called the Strategic Timing of Antiretroviral Treatment (START) study, and it’s being conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT).
The START trial is ambitious in its goal, yet simple in its basic design. Taking place at roughly 90 sites in nearly 30 countries, it seeks to randomize more than 4,000 antiretroviral-naive HIV-positive individuals with CD4s above 500 cells to either begin treatment immediately or defer treatment until their CD4s are less than 350 cells.
Some researchers associated with START are concerned that the revised DHHS guidelines will lead to conclusions among people living with HIV and their care providers that deferring treatment until the CD4 cell count hits 350 is too great of a safety gamble. “We are concerned that some may interpret the new [U.S.] recommendations as implying that the deferral group of this trial is no longer ethical,” Andrew Phillips, PhD, a statistician for the START trial, and his colleagues write in the February 20 issue of The Lancet. The authors add: “Such an interpretation would endanger the future of the trial in the USA.”
In an effort to challenge such interpretations, members of START’s Community Advisory Board (CAB) issued a sign-on letter highlighting the controversy surrounding the DHHS recommendations, allaying safety concerns and reiterating the need for sound, scientific data to determine, once and for all, when treatment should be started.
“We wanted to see whether there was still strong community support for getting proper evidence before changing policy so dramatically,” says Collins, a lead author of the letter. “We also wanted to emphasize that it is still a very safe study, whether someone is randomized to the immediate or deferred treatment groups.”
Collins and his fellow START CAB members—roughly 260 signatures have been added to the letter including more than 150 organizations—express a number of grievances with the revised DHHS guidelines and, indeed, the promotion of treatment at any CD4 cell count.
According to the sign-on letter, the new U.S. recommendation “is based on poor evidence and therefore might not be in the best interest of patients.”
Collins comments that the sign-on letter has actually shown how widely the study is supported. “Getting a study like START has been an activist priority for at least 10 years, and luckily, it is now being run when treatment is at its safest. Many activists continue to believe in the importance of this study, probably many more than those who think we already know enough without the data it will provide.”
Researchers are also on board with the study. “Researchers in the U.S. still see the study as safe and important,” Collins adds. “Many of the experts on the guidelines panel are also on the steering committee for START.”
START is proceeding in two phases. The pilot phase will ultimately enroll at least 900 participants, followed by a definitive phase, which will expand enrollment to an estimated 4,000 participants.
In addition to the primary study objective—to determine whether or not those who start therapy immediately are less likely to develop a serious AIDS illness, a serious non-AIDS illness or death from any cause—some patients enrolled in the trial will be followed closely to answer more specific questions about early treatment, including its effects on neurological, arterial, pulmonary and bone diseases.
“START is a randomized study, which isn’t just a technical detail,” Collins stresses. “It means the results will be solid and is the gold-standard for research. Otherwise, we have nothing other than guesses—and those guesses, even by experts, have been wrong too often in the past.”
START isn’t just about evaluating the potential benefits of treatment for practically everyone living with HIV, but also about its potential risks. “Cohort studies show the potential benefits of earlier treatment, but they haven’t been able to look at the risks of drug resistance or side effects,” Collins points out. “If we are asking people to start treatment when they feel well, we need to be able to know the risks too. The risks may turn out to be low, but we don’t know. Even aspirin does more harm than good if you give it to everyone, and this could easily be the case for HIV drugs.”
Collins also points out that, for people in the United States, the study provides free treatment. “This may in fact guarantee access to newer drugs and earlier treatment than they would have access to otherwise.”