A major international trial has found that starting HIV treatment early, rather than waiting until the disease has damaged the person’s immune system, reduces the risk of developing serious illnesses. These findings from the START trial were released earlier than planned as there is now sufficient evidence to support offering HIV treatment early to people diagnosed with HIV.
Antiretroviral therapy is very effective at treating HIV, but it does have side effects. Until now it has not been clear whether it is better for a person with HIV to wait until their immune system had been weakened by the disease before starting treatment for life, or to start it while they are still healthy. START is the first large-scale randomised controlled trial to establish that earlier antiretroviral treatment benefits all HIV-positive individuals.
The START trial was carried out by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) at 215 sites in 35 countries across six continents. 4,685 HIV-infected men and women took part in the study. To take part in the study, people had to have never taken HIV treatment, and also to have a CD4 count of over 500 per cubic millimetre (mm3) of blood. CD4 cells are a type of blood cell that helps to protect the body from infections. Most healthy people who are not infected with HIV have CD4 cell counts of over 500 cells/ mm3. HIV attacks the immune system, and over time reduces the CD4 count, leaving people vulnerable to other infections. Half of the study participants were randomised to start HIV treatment immediately (early treatment), and the other half were randomised to defer treatment until their CD4 cell count fell to 350 cells/ mm3. On average, participants in the study have been followed for three years. The study measured a combination of outcomes that included serious AIDS events (such as tuberculosis or AIDS-related cancer), serious non-AIDS events (major heart, kidney and liver disease and other cancers), and death.
The rate of serious illnesses and deaths was low in both groups. But there was clear evidence that starting HIV treatment early provided significant protection against serious illness. Based on data from March 2015, the Independent Data and Safety Monitoring Board found 41 instances of AIDS, serious non-AIDS events or death among those enrolled in the study’s early treatment group compared to 86 events in the deferred treatment group. Early treatment reduced the risk of developing serious illness or death by 53 percent, compared to those in the deferred group. Findings were consistent across geographic regions, and the benefits of early treatment were similar for participants from low- and middle-income countries and participants from high-income countries.
In light of these 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 through 2016, as planned. This will provide valuable additional information on early HIV treatment. The full results will be published later this year.
Abdel Babiker, professor of epidemiology and medical statistics at the MRC CTU at UCL and Co-Chair of the START study said: “We know from previous trials that ART reduces the risk of transmission of HIV. The findings from START clearly demonstrate that early treatment is also of benefit to the individual. This provides a very strong rationale for offering treatment to all HIV-positive individuals as soon as they are diagnosed”.
Current World Health Organization HIV treatment guidelines recommend that HIV-positive individuals begin antiretroviral therapy when CD4 cell counts fall to 500 cells/ mm3 or less. In the UK, national guidelines recommend starting people on treatment once their CD4 cell count falls below 350 cells/ mm3. The results from START are likely to lead to changes in these guidelines.
The University of Minnesota is the regulatory sponsor and statistical and data management centre of the trial. The Medical Research Council Clinical Trials Unit at University College London; the Copenhagen HIV Program at the Rigshospitalet, University of Copenhagen in Denmark; the Kirby Institute at the University of New South Wales in Sydney, Australia; and the Veterans Affairs Medical Center affiliated with George Washington University in Washington, D.C. coordinated the work of the 215 START sites.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health in the USA, provided primary funding for the START trial. In addition to NIAID, funding for the START trial came from other NIH entities, including the National Cancer Institute; the National Heart, Lung and Blood Institute; the National Institute of Mental Health; the National Institute of Neurological Disorders and Stroke; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the NIH Clinical Center; and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Funding was also provided by the National Agency for Research on AIDS and Viral Hepatitis (ANRS) in France, the Federal Ministry of Education and Research in Germany, the European AIDS Treatment Network and government organizations based in Australia, Denmark, and the United Kingdom.