Pulmonary hypertension in individuals with HIV infection
Petrosillo, Nicola; Chinello, Pierangelo; Cicalini, Stefania
National Institute for Infectious Diseases ‘L. Spallanzani’, 2nd Infectious Diseases Division, Rome, Italy.
Received 7 June, 2006
Accepted 7 July, 2006
In their recent review on pulmonary disease in HIV-infected patients, Grubb et al.  also deal with a disease that seems to be overrepresented in HIV patients, i.e. pulmonary hypertension (PH), reporting data on its frequency before the introduction of HAART [2–4].
PH is a well-known cardiovascular disease with a poor prognosis that occurs in HIV-infected patients with a greater frequency compared with the general population . Several confounding risk factors with HIV for the onset of PH are known, including human herpesvirus 8 (HHV8) infection and intravenous drug addiction (IVDA). HHV8 infection was demonstrated in the vascular lesions and lung parenchymal cells of patients with non-familial primary PH . Patients with a history of chronic IVDA may develop PH; pulmonary artery thrombosis is the main pathological finding in such a condition, and it is believed to be caused by foreign particle pulmonary emboli after injections of heroin solutions .
Before the introduction of HAART, the Swiss Cohort estimated a 2500-fold higher frequency of HIV-associated PH among HIV-infected individuals than that of primary PH in the general population . In the same cohort, there was a decrease in the incidence of HIV-associated PH after the introduction of HAART .
More recently, more effective therapies for PH have been available, including prostanoids, endothelin-receptor antagonists, and phosphodiesterase-5 inhibitors, allowing an amelioration of symptoms and a better prognosis . The availability of new therapeutic options, and the need for a better evaluation of the burden of PH among the HIV-infected population, led us to implement a registry of PH in HIV-infected subjects in April 2004 in a wide central Italian region (Lazio), with approximately 5 million inhabitants and an estimate of 5000 HIV-infected subjects. All regional infectious disease units participated in the registry by using a diagnostic algorithm  and basic diagnostic procedures (i.e. X-rays, echocardiography, spirometry) for the diagnosis of PH. Data were collected and sent to our referral centre.
Between April 2004 and April 2006, a total of 39 HIV-infected patients (0.8%) were found to have PH. Secondary causes of PH were identified in 28 of them, including 13 patients with cardiac causes of PH (10 valvulopathies and three dilated cardiomyopathies), eight patients with chronic obstructive pulmonary disease, and seven with other causes (pulmonary embolism, cirrhosis, and restrictive cardiomyopathy).
Eleven patients were classified as having HIV-associated PH according to the clinical classification of PH proposed in Venice in 2003 . Three of them were found to have PH during an echocardiographic screening performed in 300 consecutive HIV-infected patients with no symptoms or signs of cardiopulmonary disease in our outpatient clinic. Data on all 11 patients are shown in Table 1. The frequency of HIV-associated PH in our registry (11/5000; 0.2%) is slightly lower than that reported in the Swiss cohort before HAART . This could partly be explained by the fact that HIV-infected patients in our region are largely treated with HAART, and as observed by Zuber et al.  the incidence of HIV-associated PH has been reduced since the introduction of HAART. However, we also found three individuals with asymptomatic HIV-associated PH during an echocardiographic screening, suggesting that this cardiovascular condition could be more frequent than expected, and is probably latent for many years. Asymptomatic HIV-associated PH patients were younger (38 ± 3.6 versus 41 ± 6.6 years, P = 0.4), and had significantly lower HIV viraemia (1038 ± 909 versus 54726 ± 45339 copies/ml, P = 0.01) than symptomatic HIV-associated PH patients.
As PH could complicate the course of HIV infection regardless of the degree of immunosuppression, and represents a significant cause of morbility and mortality , research on PH should be incorporated into the clinical management of HIV-infected patients with dyspnoea. Furthermore, improved awareness should lead to increased referral to specialized centres to initiate specific management and therapies in order to enhance the quality of life, exercise capacity, and survival.
Sponsorship: This work was supported by Ricerca Corrente IRCCS.
1. Grubb JR, Moorman AC, Baker RK, Masur H, and the HOPS investigators. The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy. AIDS 2006; 20:1095–1107.
2. Speich R, Jenni R, Opravil M, Pfab M, Russi EW. Primary pulmonary hypertension in HIV infection. Chest 1991; 100:1268–1271.
3. Rubin LJ. Primary pulmonary hypertension. N Engl J Med 1997; 336:111–117.
4. Opravil M, Pechere M, Speich R, Joller-Jemelka HI, Jenni R, Russi EW, et al. HIV-associated primary pulmonary hypertension. A case–control study. Swiss HIV cohort study. Am J Respir Crit Care Med 1997; 155:990–995.
5. Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, et al. Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 2003; 349:1113–1122.
6. Pellicelli AM, Palmieri F, Cicalini S, Petrosillo N. Pathogenesis of HIV-related pulmonary hypertension. Ann NY Acad Sci 2001; 946:82–94.
7. Zuber JP, Calmy A, Evison JM, Hasse B, Schiffer V, Wagels T, et al. Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy. Clin Infect Dis 2004; 38:1178–1185.
8. Rubin LJ, Badesch MD. Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med 2005; 143:282–292.
9. Petrosillo N, Chinello P, Vizza D, Cicalini S. Pulmonary hypertension and HIV: implementation of a regional registry. Infez Med 2005; 13:5–15.
10. Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43(Suppl S):5S–12S.
11. Nunes H, Humbert M, Sitbon O, Morse JH, Deng Z, Knowles JA, et al. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2003; 167:1433–1439.
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