Starting HIV treatment straight away, rather than waiting until the disease has damaged the person's immune system, reduces the risk of developing serious illnesses. These results from the START trial were presented yesterday at the International AIDS Society conference in Vancouver and published in the New England Journal of Medicine..
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 whose immune system is still in tact to wait until their immune system had been weakened by the disease before starting treatment for life, or to start it as soon as possible. START is the first large-scale randomised controlled trial to establish that starting antiretroviral treatment straight away benefits HIV-infected individuals regardless of the state of their immune system.
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-positive 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.
Study participants were randomised to either:
- start HIV treatment immediately (early treatment),
- or wait until their CD4 cell count fell to 350 cells/ mm3 to start treatment (deferred treatment)
On average, participants in the study have been followed on average 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 (1.8% of participants in the early treatment group and 4.1% in the deferred group). But there was clear evidence that starting HIV treatment early provided significant protection: it more than halved serious illnesses and deaths. The biggest difference was in the rate of serious AIDS-related illnesses, which was 72% lower in people who started treatment early. There were few deaths from any cause in either arm (12 in the early treatment arm vs 21 in the deferred treatment arm).
The findings were consistent across geographic regions. The benefits of early treatment were similar for participants from low- and middle-income countries and participants from high-income countries, which means these results are of global relevance.
The most common serious illnesses seen in the trial were cardiovascular disease, cancers not usually associated with AIDS, and tuberculosis. These did vary by geographic region. Most of the tuberculosis cases occurred in Africa, while most of the cancers and cardiovascular illnesses occurred in Australia, Europe, Israel and the USA.
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-infected individuals as soon as they are diagnosed".
Current World Health Organization HIV treatment guidelines recommend that HIV-infected individuals begin antiretroviral therapy when CD4 cell counts fall to 500 cells/ mm3 or less. These are being updated, and the START results will be considered as part of that process. In the UK, current national guidelines recommend starting people on treatment once their CD4 cell count falls below 350 cells/ mm3. The British HIV Association recently released updated draft guidelines for consultation, recommending immediate treatment, based on the START results.
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 (the Medical Research Council and the National Institute for Health Research).