People with HIV should be put on antiretroviral drugs as soon as they learn they are infected, US health officials said as they announced that they were halting the largest ever clinical trial of early treatment because its benefits were already so clear. The New York Times reports that the study was stopped more than a year early because preliminary data already showed that those who got treatment immediately were 53% less likely to die during the trial or develop Aids or a serious illness than those who waited.
The study is strong evidence that early treatment saves more lives, the officials said. Fewer than 14m of the estimated 35m people infected with HIV around the world are on treatment now, according to UNAIDS, the UN Aids-fighting agency. In the US, only about 450,000 of the estimated 1.2m with HIV are on treatment, according to the Centres for Disease Control and Prevention (CDC). “This is another incentive to seek out testing and start therapy early, because you will benefit,” said Dr. Anthony S Fauci, director of the National Institute for Allergy and Infectious Disease, which sponsored the trial. “The sooner, the better.”
Although the CDC recommends immediate treatment, it said late last year that only 37% of infected Americans had prescriptions for the drugs. The agency blamed a mix of factors, including HIV-positive people missed by testing, those who had no health insurance and therefore did not see doctors or could not afford the drugs, and those whose doctors were unfamiliar with treatment guidelines.
Internationally, there is not nearly enough money even to put those who are already sick on antiretroviral medicines, much less those not yet showing symptoms. The Global Fund to Fight AIDS, Tuberculosis and Malaria is in a constant struggle to raise money and the President’s Emergency Plan for AIDS Relief has been essentially flat since 2010. Putting all the people with HIV in the world’s poor and middle-income countries on treatment immediately would cost almost $20bn, about triple the $6.3bn per year that is now being spent on that, UNAIDS said.
“This is a defining moment for social justice,” said Michel Sidibé, executive director of UNAIDS. “People will be scared, saying, ‘Oh, it will be a big number.’ But this puts an end to the false debate about whether to pay for treatment.” Many Aids researchers and advocates have long argued – based on their own observations and smaller studies – that treatment should start immediately. This trial is the first major clinical trial to produce evidence that patients would live longer and be healthier if they did so.
Dr Julio SG Montaner, a former president of the International AIDS Society who wrote a seminal 2006 paper in The Lancet arguing that universal antiretroviral treatment was the best way to curb the AIDS epidemic, said the study “confirms what we have been saying for years.”
The trial has found that HIV-infected people have a considerably lower risk of developing Aids or other serious illnesses if they start taking antiretroviral therapy (ART) sooner, when their CD4+ T-cell count is higher, instead of waiting until the CD4+ cell count drops to lower levels. The study shows unequivocally that starting HIV therapy before a person’s CD4 count drops below 500 cells/mm3 leads to less illness and fewer adverse events, both Aids- and non-Aids-defining, in patients, compared to waiting till their CD4 count drops below 350 cells/mm3. These results are likely to have a major impact on international treatment guidelines.
The Strategic Timing of AntiRetroviral Treatment (START) study, was a large-scale randomised clinical trial that tested whether earlier ART benefited all people with HIV. Its predecessor, the SMART study, had a massive impact when it showed in 2006 that staying on ART was better than interrupting it. Like SMART, START was stopped early; though it was expected to end in December 2016, an interim review of the study data by the study’s Independent Data and Safety Monitoring Board (DSMB) recommended that results be released early.
START, which opened widely in March 2011, was conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) at 215 sites in 35 countries. The trial enrolled 4,685 men and women with HIV who had never taken ART. They were 18 and older, with a median age of 36, and their CD4 counts were all over 500 cells/mm3. Half of the study participants were randomised to start ART immediately and the other half deferred treatment until their CD4+ cell count declined to 350 cells/mm3. On average, participants in the study were followed for three years.
The study measured a combination of outcomes that included serious Aids events (such as Aids-related cancer), serious non-Aids events (major cardiovascular, renal and liver disease and cancer), and death. Based on data from March 2015, the DSMB found 41 instances of Aids, serious non-Aids events or death among those enrolled in the group starting ART early compared to 86 events in those deferring it. This equates to a reduction if 53% in the risk of developing serious illness or death. The risk reduction was even more pronounced for the Aids-defining illnesses. Findings were consistent across sites and the benefits of early ART were similar for people from low-, middle- and high-income countries.
“We now have clear-cut proof that it is of significantly greater health benefit to an HIV-infected person to start antiretroviral therapy sooner rather than later,” said NIAID director, Fauci. He added: “Moreover, early therapy conveys a double benefit, not only improving the health of individuals but at the same time, by lowering their viral load, reducing the risk they will transmit HIV to others. These findings have global implications for the treatment of HIV.”
“This is an important milestone in HIV research,” said Dr Jens Lundgren, of the University of Copenhagen and one of the co-chairs of the START study. “We now have strong evidence that early treatment is beneficial to the HIV-positive person. These results support treating everyone irrespective of CD4+ T-cell count.”
Current World Health Organisation HIV treatment guidelines recommend that HIV-infected people start ART when their CD4 counts fall to 500 cells/mm3, but some guidelines, including the current British HIV Association (BHIVA) guidelines, still recommend waiting until CD4 counts fall below 350 cells/mm3. In light of the DSMB findings, study investigators are informing all participants of the interim results. Participants will be offered treatment if they are not already on antiretroviral therapy, and they will continue to be followed till the end of 2016.
The Desmond Tutu HIV Foundation (DTHF) Clinical Trials Unit has been a major participant in this important international clinical trial. The DTHF says the results will have a considerable impact on the management of HIV treatment in the future. The DTHF Clinical Trials Unit enrolled 287 participants in the study, the largest number at any site. The site also served as the Site Coordinating Centre for two other South African sites, Clinical HIV Research Unit in Johannesburg and the Durban International Clinical Research Site. In total, South Africa enrolled 501 participants on the study.
‘This is a very encouraging result which will inform policy based on good quality data,’ said Professor Robin Wood, CEO of the Desmond Tutu HIV Foundation and principal investigator for the site in Cape Town. ‘We now have strong evidence that early treatment is beneficial to the HIV-positive person.’
The DTHF says in the light of these findings, all our participants are being informed of these results. They will be offered treatment if they are not already on antiretroviral therapy and they will continue to be followed up on study until the end of 2016.
According to a Groundup report, the study will continue because it aims to answer several other questions dealing with how HIV affects the kidneys, lungs, bones, liver, heart and brain. One in five patients on the trial is in Africa, with the Desmond Tutu HIV Centre in Cape Town having the largest number of participants of any site worldwide. A third of the participants are in Europe and a quarter in South America and Mexico. There are also participants in the US, Asia and Australia. Professor Francois Venter, former president of the Southern African HIV Clinicians Society, who is also on the START DSMB, described the results as “amazing” and “unexpected”.
The report says in recent years, medical researchers, including Ben Goldacre, the author of the influential books Bad Science and Bad Pharma, have called for large clinical trials which answer straightforward questions of important to public health. START is an example of such a trial.