A low CD4 cell count is associated with a poor prognosis for HIV-positive patients diagnosed with pulmonary arterial hypertension, French investigators report in the January edition of AIDS. The study also showed that the condition developed in patients taking antiretroviral therapy, which did not, by itself, provide an effective treatment for pulmonary arterial hypertension.
Pulmonary arterial hypertension results from the obstruction of the small pulmonary arteries. This can lead to the failure of the right ventricle (one of the four chambers of the heart) and ultimately lead to death.
HIV infection is an independent risk factor for the development of pulmonary arterial hypertension. However, little is known about the condition in the era of modern antiretroviral therapy.
Investigators from a French national treatment centre for pulmonary arterial hypertension therefore performed a retrospective study to determine the incidence, risk factors, optimum treatment, outcome and prognostic factors for HIV-infected individuals diagnosed with the condition.
Between 2000 and 2008 a total of 944 patients were referred to the unit. Of these 77 (8%) had HIV as they only risk factor for pulmonary arterial hypertension.
Injecting drug use was the most common HIV-associated risk behaviour (36%) and 49% of the patients were co-infected with hepatitis B or hepatitis C virus.
At the time pulmonary arterial hypertension was diagnosed, 62% of patients were taking antiretroviral therapy and 49% had a viral load below 50 copies/ml with 79% having a CD4 cell count above 200 cells/mm3.
“This observation confirms that pulmonary arterial hypertension can develop in patients with well controlled HIV infection, and that HAART [highly active antiretroviral therapy] is unable to prevent the development of pulmonary arterial hypertension”, comment the investigators.
An established assessment of the functional status of patients with heart disease is that of the New York Heart Association. In all, 9% of HIV-infected patients with pulmonary arterial hypertension were in category IV, which is indicative of very poor functioning.
Patients in this category were significantly older (p = 0.02), had a longer duration of HIV infection (p = 0.02), were more likely to have a history of heart failure (p < 0. 01), had a poorer six-minute walk distance assessment (p < 0.0001), as well as poorer haemodynamic measurements (p = 0.01 to p < 0.01).
Antiretroviral therapy was immediately started by the 15 patients who were not already taking it at the time of their diagnosis.
Specific treatment for pulmonary arterial hypertension was started by 50 patients, the most common being bosentam (45 individuals).
Treatment with antiretroviral therapy alone increased the six-minute walk distance by a significant 18% (p = 0.04). However, it did not significantly alter haemodynamic parameters.
At the end of follow-up, 26 patients had died and two had been lost to follow-up. Fifteen of the 26 deaths were judged to be a consequence of hypertension. The investigators calculated that the overall one-year survival rate was 88%, the three-year rate 72%, and that 63% of individuals were alive after five years.
These outcomes, the investigators note, are better than those seen in some other studies of HIV-infected patients with pulmonary arterial hypertension.
However, the 63% five-year survival rate was significantly below the 85% survival rate that would be expected in HIV-infected patients at diagnosis of a first opportunistic infection.
Statistical analysis that controlled for potentially confounding factors showed that a CD4 cell count below 200 cells/mm3 (odds ratio [OR], 6.26; 95% CI: 2.33 – 16.64, p = 0.0002) and a cardiac index below 2.81 l/m per m2 (OR, 5.02; 95% CI: 1.70 – 14.29, p = 0.0028) were significant risk factors for poorer survival.
“Pulmonary arterial hypertension remains a complication of HIV infection that burdens the prognosis of HIV-infected patients”, write the investigators.
“Data from the current series indicate that HAART is very unlikely to improve haemodynamic parameters in pulmonary arterial hypertension-HIV patients”, they add.
They call for further studies to determine if “specific pulmonary arterial hypertension therapy might be of benefit to HIV-infected patients with mildly symptomatic pulmonary arterial hypertension”. They also recommend careful follow-up of all patients with mild hypertension not receiving anti-hypertensive treatment after starting antiretroviral treatment.
Degano B et al. HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era. AIDS 24: 67-75, 2010.