The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), USA, has prematurely stopped the largest, international, randomized clinical trial known as the Strategic Timing of AntiRetroviral Treatment (START) study when results from the interim review by an independent data and safety monitoring board (DSMB) saw that there were significant differences between the immediate arm (group of patients that started antiretroviral therapy immediately or early after learning of their HIV status) and the deferred arm (group of patients who waited until their CD4 dropped to 350 level to start antiretroviral therapy). These differences were alarmingly so strong that the trial was immediately halted to protect the deferred patients from further harm. Therefore the study was stopped so that the deferred patients can start antiretroviral therapy. The Director of the NIH, Dr. Anthony S Fauci, made the announcement on May 30, 2015 via the telephone news conference that 53% of the patients were less likely to die or develop AIDS or any other serious illnesses (i.e., Karposi’s sarcoma, tuberculosis, and/or various pneumonias) if they started HIV treatment immediately.
HIV-NAT is one of the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) sites participating in the START study (NCT00867048) since 2009. The START study has a total of 215 sites in 35 countries with 4,685 HIV-infected men and women older than 18 years old. Half of the patients were randomly picked to start treatment early while others waited until their CD4 level dropped to 350. At the time when the study was developed, the World Health Organization (WHO) treatment guidelines indicated to start antiretroviral therapy when CD4 was less or equal to 200 cells per cubic millimeter (cells/mm3) whereas in the US, it was already at 350 cells/mm3. However, the time to initiate treatment has been a long, controversial topic among the scientific community. Not shortly after, the US changed its time to initiate treatment to 500 cells/mm3. In 2013, WHO amended its guidelines to start treatment at 500 but acknowledged that 350 was more practical based only on observational findings. By this time, the US had changed its guidelines to start antiretroviral therapy regardless of CD4 count. Thailand also followed suit and amended its guidelines to initiate HIV treatment regardless of CD4 count. Nevertheless, the patients from the START study continued to follow the study protocol of starting treatment when CD4 dropped to 350 cells/mm3. So far the patients already in the study have had an average follow-up duration of 3 years. The study’s expected closing date was set for the end of 2016. Now the most challenging part is to achieve the first “90:90:90” (90% will know their HIV status; 90% will be on HIV treatment; and 90% on treatment will have suppressed viral load) target of UNAIDS.
HIV-NAT has already started to contact its patients in the deferred arm to initiate antiretroviral therapy immediately. WHO has announced that it will issue its new treatment guidelines next month based on this important finding.
For more information: http://www.niaid.nih.gov/news/QA/Pages/STARTqa.aspx
