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

Oct 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/perl… journal.pmed.0050203

Source: Public Library of Science

Explore further: Condoms 'too small' for Uganda men

add to favorites email to friend print save as pdf

Related Stories

3-in-1 optical skin cancer probe

Aug 05, 2014

As thousands of vacationers hit the beach this summer, many of them will expose their unprotected bare limbs to direct UV sunlight, potentially putting them at risk of skin cancer later in life. To fight ...

Mental-health monitoring goes mobile

Jul 16, 2014

Behavioral health analytics startup Ginger.io sees smartphones as "automated diaries" containing valuable insight into the mental well-being of people with mental illnesses.

Team uses nanoparticles to enhance chemotherapy

Jul 07, 2014

(Phys.org) —University of Georgia researchers have developed a new formulation of cisplatin, a common chemotherapy drug, that significantly increases the drug's ability to target and destroy cancerous cells.

New study may improve rice productivity

Jun 23, 2014

University of Illinois researchers established the university's first rice paddy to test rice performance in Illinois and at Kyoto University in Japan. The two plots, which were planted on the same date, ...

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0