Antiretroviral Therapy Does Not Improve HIV-associated Pulmonary Arterial Hypertension, but High CD4 Cell Count Reduces Mortality

Despite the advent of combination highly active antiretroviral therapy (HAART), people with HIV still develop pulmonary arterial hypertension, a potentially fatal condition characterized by obstruction causing high blood pressure in the small arteries of the lungs. HAART alone did not improve pulmonary hypertension, researchers reported in the January 2, 2009 issue of AIDS, but people with higher CD4 counts had a better prognosis, underlining the benefit of starting treatment before serious immune deficiency develops.

Bruno Degano from Hôpital Antoine-Béclère in Paris and colleagues examined baseline characteristics and outcomes of HIV-associated pulmonary arterial hypertension, aiming to determine variables affecting survival in the HAART era.

Over time, pulmonary hypertension can cause damage to the right ventricle of the heart, which can result in heart failure. Prior research has shown that HIV infection is a risk factor for pulmonary hypertension, but it is not clear whether HAART affects its occurrence or outcome.

This retrospective analysis included data from 77 consecutive HIV positive patients treated at the French Reference Centre for Pulmonary Hypertension between October 2000 and January 2008 who had no other known risk factors for pulmonary arterial hypertension.

At the time of pulmonary arterial hypertension diagnosis, 81% of the patients were on HAART, 79% had a CD4 count > 200 cells/mm3, and 49% had undetectable HIV viral load; about half were coinfected with hepatitis B or C. The remainder started combination antiretroviral therapy during pulmonary hypertension management, regardless of HIV disease stage or CD4 count.

Results

• 22% of patients had mild symptoms of heart failure such as angina (chest pains) and shortness of breath (New York Heart Association functional class II).
• 69% had more advanced symptoms that limited daily activities (class III).
• 9% had severe limitations, such as experiencing symptoms even while at rest (class IV).
• The median 6-minute walk distance was 375 meters (about 1230 feet).
• Median pulmonary vascular resistance was 689 dyn s/cm5.
• 50 patients started specific therapy for pulmonary arterial hypertension, which led to improvements in walk distance and hemodynamic parameters.
• Among patients who received HAART but not specific pulmonary hypertension therapy, walk distance improved by 18% but hemodynamics did not change.
• Overall survival rates were 88% at 1 year, 72% at 3 years, and 63% at 5 years.
• In a multivariate analysis, having a CD4 cell count > 200 cells/mm3 and a cardiac index more than 2.8 l/min per m2 were independent predictors of survival.

Based on these findings, the investigators concluded, "In patients with [HIV-associated pulmonary arterial hypertension], HAART seems unable to improve hemodynamic parameters."

"Prognosis in [HIV-associated pulmonary arterial hypertension] is mainly related to CD4 lymphocyte count and cardiac function," they added.

While the outcomes seen here were better than those from some prior studies of people with HIV, the authors noted in their discussion, survival was significantly lower than that of HIV negative people (5-year survival 63% vs 85%).

Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Service de Pneumologie, Hôpital Antoine-Béclère, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Clamart, France.

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Reference

B Degano, M Guillaume, L Savale, and others. HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era. AIDS 24(1): 67-75 (Abstract]. January 2, 2009.http://journals.lww.com/aidsonline/pages/articleviewer.aspx?year=2010&issue=01020&article=00009&type=abstract