Pulmonary arterial hypertension (PAH), a relatively rare - but very serious - complication of HIV infection is no less common now than it was before HAART, French researchers have discovered. Pulmonary arterial hypertension is a condition where the blood pressure rises in the arteries carrying oxygen-deprived blood away from the heart to be replenished in the lungs.
It’s a condition that can be inherited but can also be associated with other conditions including HIV infection.
In the mid 90s, before the advent of triple combination antiretroviral therapy it was estimated that the prevalence of the condition in patients with HIV was around 0.5%, that is one in 200 patients developed it.
This is much higher than the incidence in the general population, where there are one or two cases per million.
It is also a much more serious disease in HIV infection and according to a Spanish study published in 2003, just over half the individuals who developed the condition died within three years
Clinicians had hoped the success of HAART over the past decade had reduced the likelihood of developing PAH.
Last year researchers screened 7,648 HIV patients from 14 centres across France and found 739 of them were suffering from breathlessness - the most common early sign of PAH.
These patients were investigated further, firstly by having an echocardiogram and if PAH was suspected another test, right heart catheterisation. This involves passing a catheter through a vein into the right side of the heart and then into the pulmonary artery to check the pressure.
Thirty-five of these patients were found to have PAH , which means the prevalence is now 0.46% - not significantly different from a decade ago.
The data was presented at the American Thoracic Society meeting in San Diego last month (20-24 May 2006).
Lead author Dr Olivier Sitbon, respiratory consultant at the Hospital Antoine Beclere, Paris, said: “The results are perhaps disappointing but we have shown that the screening method we’ve used is useful and can identify these patients.”
He emphasised that any HIV-infected patient who is feeling breathless for no apparent reason should contact their doctor and doctors themselves should have a low threshold for suspecting PAH.
Dr Sitbon said the reason HIV causes the pulmonary arteries to become thickened and narrowed, leading to the rise in pressure, is unknown.
“PAH is seen in all groups of people with HIV infection, irrespective of the cause of infection or the degree of immunodefiency,” he said.
They also derive less benefit from conventional therapies than non-HIV infected PAH patients.
But Dr Sitbon says newer treatments for PAH seem to work better and long-term safety data in HIV patients - also presented at the American Thoracic Society meeting - suggest they are safe.
Bosentan (Tracleer) is an oral drug used to treat PAH, termed a dual endothelin receptor antagonist. It works by blocking the action of endothelin, a hormone which occurs in higher levels in people with PAH and damages the lung and pulmonary arteries.
Two years ago a trial of the drug in 16 people with HIV infection who had developed PAH was published.
It showed that the new drug had significant impacts on patients’ exercise capacity, (how far they could walk) and their quality of life, and the functioning of their heart improved as measured by echocardiography.
Dr Sitbon says: ‘It was a short trial at 16 weeks of treatment but it showed that this new treatment had a positive impact on the condition for people with HIV.’
Elevated liver enzymes have been reported in people receiving long term treatment with bosentan. The latest two-year data reported at the American Thoracic Society meeting shows that the frequency of raised liver enzymes was in fact lower in HIV-infected patients, at 34% of HIV-positive patients compared to 44% of those patients who were not HIV-infected, despite the use of concomitant medications also associated with elevated liver enzymes among the HIV-positive group.
Sitbon O et al. Prevalence of pulmonary arterial hypertension in HIV positive outpatients in the Highly Active Antiretroviral Therapy Era. American Thoracic Society International Conference, San Diego, abstract 807, 2006.
Humbert, MD et al. Safety profile of bosentan in patients with pulmonary arterial hypertension related to HIV: long-term results from the Tracleer PMS database. American Thoracic Society International Conference, San Diego, abstract A728, 2006.
Nunes H et al. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Crit Care Med 2003: 167:1433-1439, 2003
Sitbon A et al. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Resp Crit Care Med 170:1212-1217, 2004.