HIV may also lead to non-AIDS dieseases

Continuous HIV treatment may protect patients from other diseases

(Oct. 20, 2008) — After analyzing deaths on a large international trial of treatments for HIV-positive patients, University of Minnesota School of Public Health researchers have found a strong association between certain protein levels and increased risk of death from non-AIDS diseases such as cardiovascular problems and renal failure.

The research, published in PLoS Medicine today, may explain why interrupting antiretroviral therapy (ART) was found to increase the risk of death from non-AIDS diseases for people living with HIV.

“There is a growing body of evidence that indicates that HIV impacts a number of diseases besides AIDS-defining conditions,” said James Neaton, Ph.D., principal investigator and researcher at the University of Minnesota School of Public Health. “The data from this biomarker study support that line of thinking.”

The Strategies for Management of Anti-Retroviral Therapy (SMART) trial was carried out by the International Network for Strategic Initiatives in Global HIV Trials. SMART compared two different methods of treating HIV: continuous therapy — the current practice aimed at viral suppression — or intermittent treatment aimed at reducing drug side effects while minimizing risk of AIDS.

Unexpectedly more people assigned to intermittent treatment in the trial died, mostly from non-AIDS diseases, leading to early closure of the trial. In the follow-up study, Neaton and colleagues investigated the hypothesis that the increased risk of death among participants who received intermittent ART was due to inflammatory response caused by increased levels of HIV in the periods when ART was stopped.

Taking blood samples from the 85 people who died during the SMART trial and a control group of 170 patients who had survived, the researchers used biomarkers — levels of proteins that indicate the presence of inflammation or increased coagulation of blood — to test his hypothesis. Across both treatment groups, increased risk of death was associated with three biomarkers: high-sensitivity C-reactive protein, interleukin 6 (IL-6), and D-dimer. Measuring the same biomarkers in the blood of 499 randomly chosen patients from the trial, the researchers found that IL-6 and D-dimer levels in patients in the intermittent treatment group were increased in the first month of the trial but were unchanged in the patients who received continuous ART treatment.

“The magnitude of the increased risk of death associated with elevations of these biomarkers is clinically relevant,” Neaton said. “Research aimed at understanding whether treating elevated levels of these markers is beneficial and is now needed.”

Neaton attributed the success of this study to the strong multi-disciplinary collaborative team that designed and carried out the research.

The study was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health.