Study links inflammation and coagulation to non-AIDS deaths in people with HIV

October 21, 2008

In an analysis of deaths occurring during a large international trial of treatments for HIV-positive patients, researchers have found a strong association between markers of inflammation and coagulation and increased risk of death from non-AIDS diseases, including cardiovascular problems. The research, published in the open access journal PLoS Medicine, may explain why interrupting antiretroviral therapy (ART) was found to increase the risk of death from non-AIDS diseases for people living with HIV.

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: either continuous ART – the current practice, aimed at viral suppression – or intermittent treatment aimed at drug conservation.

For the drug conservation strategy, ART was stopped until a patient's CD4 cell count, an indicator of immune system function, dropped below 250 cells per microliter (about a quarter of the normal adult level). At that time ART was re-initiated until the CD4 cell count returned to more than 350 cells. 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 current follow-up study, James Neaton of the University of Minnesota and colleagues investigated the hypothesis that the increased risk of death among the participants who received intermittent ART was due to an 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 – including 30 who had been assigned to receive continuous ART 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 this hypothesis. Across both treatment groups, increased risk of death was associated with three biomarkers: high-sensitivity C-reactive protein (hsCRP), 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 arm increased in the first month of the trial but were unchanged in the patients who received continuous ART treatment.

"The magnitude of the association between these biomarkers and mortality is clinically relevant and reasons for it require further study," conclude the researchers of the link between the biomarkers of inflammation and the risk of death from non-AIDS diseases. Whilst the association is strong in a number of analyses, they warn that the relatively small number of deaths among participants in the study's continuous treatment group means that the biomarker results should be treated with caution and confirmed in other studies before they can be applied to people taking currently recommended ART regimens. However, the findings raise the possibility that the development of therapies that reduce overactive inflammation and coagulation associated with HIV infection may extend the life expectancy of people living with HIV.

Citation: Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, et al. (2008) Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med 5(10): e203. doi:10.1371/journal.pmed.0050203
medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050203

Source: Public Library of Science

Explore further: 3D acquisition of forensic evidence presents crime scene analysts with new perspectives

Related Stories

How journals shape science and academia

June 1, 2015

No matter whether you study medicine or biology, law or art, neuroscience or history—there is one instrument that we all share: the journal. Learned journals play a pivotal role in science and academia. Publishing in scholarly ...

The ethical slipperiness of hoaxes

June 1, 2015

Hoaxes sure can stir up a lot of emotion, can't they? We tend to have a quick reaction to them, and they flush out differences in values quickly, too.

Healing plants inspire new compounds for psychiatric drugs

May 11, 2015

Treatments used by traditional healers in Nigeria have inspired scientists at Northwestern University to synthesize four new chemical compounds that could one day lead to better therapies for people with psychiatric disorders.

London launches hi-tech trial for pedestrian safety

March 11, 2014

(Phys.org) —London is trying out intelligent pedestrian technology to make crossing the road easier and safer. Announced earlier this month, the technology is said to be the first scheme of its kind in the world. The Mayor ...

Recommended for you

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

Quantum Theory May Explain Wishful Thinking

April 14, 2009

(PhysOrg.com) -- Humans don’t always make the most rational decisions. As studies have shown, even when logic and reasoning point in one direction, sometimes we chose the opposite route, motivated by personal bias or simply ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.