Pulmonary arterial hypertension associated with human immunodeficiency virus
- Michael Ieong, MD
Michael Ieong, MD
- Assistant Professor of Medicine
- Boston University School of Medicine
- Harrison W Farber, MD
Harrison W Farber, MD
- Professor of Medicine
- Boston University School of Medicine
Human immunodeficiency virus-related pulmonary arterial hypertension (HIV-PAH) exists when pulmonary arterial hypertension (PAH) develops in a patient who has human immunodeficiency virus (HIV) infection and an alternative cause cannot be identified. More than 200 cases have been reported since its initial description in 1987 [1-4].
In this topic review, the classification, prevalence, pathogenesis, clinical presentation, diagnostic evaluation, and treatment of HIV-PAH are discussed. Pulmonary hypertension that is unrelated to HIV infection is discussed separately. (See "Overview of pulmonary hypertension in adults" and "Treatment of pulmonary hypertension in adults" and "Clinical features and diagnosis of pulmonary hypertension in adults" and "Pathogenesis of pulmonary hypertension".)
The World Health Organization (WHO) classifies patients with pulmonary hypertension into five groups based upon etiology (table 1) . Patients in the first group are considered to have pulmonary arterial hypertension (group 1 PAH), while patients in the remaining four groups are considered to have pulmonary hypertension (group 2, 3, 4, and 5 PH). When all five groups are discussed collectively, the term PH is used. (See "Overview of pulmonary hypertension in adults", section on 'Classification'.)
Human immunodeficiency virus-related pulmonary arterial hypertension (HIV-PAH) is a type of PAH. It is a member of the "associated with PAH" subgroup that includes diseases that have an increased prevalence of coexisting PAH (table 1) . Also included in the subgroup is PAH associated with drugs and toxins, connective tissue diseases, portal hypertension, congenital heart disease, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn, pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis. (See "Portopulmonary hypertension" and "Pulmonary arterial hypertension in systemic sclerosis (scleroderma): Definition, classification, risk factors, screening, and prognosis".)
Human immunodeficiency virus-related pulmonary arterial hypertension (HIV-PAH) is a rare complication of HIV infection, occurring in approximately 1 out of every 200 HIV-infected patients (0.5 percent) [6-10]. This is 6- to 12-times greater than the prevalence of PAH in individuals without HIV infection.
- Kim KK, Factor SM. Membranoproliferative glomerulonephritis and plexogenic pulmonary arteriopathy in a homosexual man with acquired immunodeficiency syndrome. Hum Pathol 1987; 18:1293.
- Mehta NJ, Khan IA, Mehta RN, Sepkowitz DA. HIV-Related pulmonary hypertension: analytic review of 131 cases. Chest 2000; 118:1133.
- Humbert M, Sitbon O, Chaouat A, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006; 173:1023.
- Petrosillo N, Chinello P, Cicalini S. Pulmonary hypertension in individuals with HIV infection. AIDS 2006; 20:2128.
- Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013; 62:D34.
- Speich R, Jenni R, Opravil M, et al. Primary pulmonary hypertension in HIV infection. Chest 1991; 100:1268.
- Barbarinia G, Barbaro G. Incidence of the involvement of the cardiovascular system in HIV infection. AIDS 2003; 17 Suppl 1:S46.
- Sitbon O, Lascoux-Combe C, Delfraissy JF, et al. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med 2008; 177:108.
- Mesa RA, Edell ES, Dunn WF, Edwards WD. Human immunodeficiency virus infection and pulmonary hypertension: two new cases and a review of 86 reported cases. Mayo Clin Proc 1998; 73:37.
- Himelman RB, Dohrmann M, Goodman P, et al. Severe pulmonary hypertension and cor pulmonale in the acquired immunodeficiency syndrome. Am J Cardiol 1989; 64:1396.
- Isasti G, Moreno T, Pérez I, et al. High prevalence of pulmonary arterial hypertension in a cohort of asymptomatic HIV-infected patients. AIDS Res Hum Retroviruses 2013; 29:231.
- Schwarze-Zander C, Pabst S, Hammerstingl C, et al. Pulmonary hypertension in HIV infection: a prospective echocardiographic study. HIV Med 2015; 16:578.
- Selby VN, Scherzer R, Barnett CF, et al. Doppler echocardiography does not accurately estimate pulmonary artery systolic pressure in HIV-infected patients. AIDS 2012; 26:1967.
- Burkart KM, Farber HW. HIV-associated pulmonary hypertension: diagnosis and treatment. Adv Cardiol 2003; 40:197.
- Marecki JC, Cool CD, Parr JE, et al. HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques. Am J Respir Crit Care Med 2006; 174:437.
- Wang Y, Luo Y, Yuan Y, et al. [Measurement and clinical significance of inspiratory drive efficacy in patients with chronic obstructive pulmonary disease]. Hua Xi Yi Ke Da Xue Xue Bao 1997; 28:434.
- Mette SA, Palevsky HI, Pietra GG, et al. Primary pulmonary hypertension in association with human immunodeficiency virus infection. A possible viral etiology for some forms of hypertensive pulmonary arteriopathy. Am Rev Respir Dis 1992; 145:1196.
- Humbert M, Monti G, Fartoukh M, et al. Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 1998; 11:554.
- Ehrenreich H, Rieckmann P, Sinowatz F, et al. Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. J Immunol 1993; 150:4601.
- Caldwell RL, Gadipatti R, Lane KB, Shepherd VL. HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells. J Leukoc Biol 2006; 79:192.
- Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 2000; 67:737.
- Kimura N, Matsuo R, Shibuya H, et al. BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6. J Biol Chem 2000; 275:17647.
- Almodovar S, Knight R, Allshouse AA, et al. Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension. AIDS Res Hum Retroviruses 2012; 28:607.
- Weiss RA, Whitby D, Talbot S, et al. Human herpesvirus type 8 and Kaposi's sarcoma. J Natl Cancer Inst Monogr 1998; :51.
- Cool CD, Rai PR, Yeager ME, et al. Expression of human herpesvirus 8 in primary pulmonary hypertension. N Engl J Med 2003; 349:1113.
- Henke-Gendo C, Mengel M, Hoeper MM, et al. Absence of Kaposi's sarcoma-associated herpesvirus in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2005; 172:1581.
- Katano H, Hogaboam CM. Herpesvirus-associated pulmonary hypertension? Am J Respir Crit Care Med 2005; 172:1485.
- Montani D, Marcelin AG, Sitbon O, et al. Human herpes virus 8 in HIV and non-HIV infected patients with pulmonary arterial hypertension in France. AIDS 2005; 19:1239.
- Morse JH, Barst RJ, Itescu S, et al. Primary pulmonary hypertension in HIV infection: an outcome determined by particular HLA class II alleles. Am J Respir Crit Care Med 1996; 153:1299.
- Humbert M, Monti G, Brenot F, et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med 1995; 151:1628.
- Pellicelli AM, Palmieri F, Cicalini S, Petrosillo N. Pathogenesis of HIV-related pulmonary hypertension. Ann N Y Acad Sci 2001; 946:82.
- Zuber JP, Calmy A, Evison JM, et al. Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy. Clin Infect Dis 2004; 38:1178.
- Badesch DB, Champion HC, Sanchez MA, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2009; 54:S55.
- Nunes H, Humbert M, Sitbon O, et al. Prognostic factors for survival in human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2003; 167:1433.
- Degano B, Guillaume M, Savale L, et al. HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era. AIDS 2010; 24:67.
- Mondy KE, Gottdiener J, Overton ET, et al. High Prevalence of Echocardiographic Abnormalities among HIV-infected Persons in the Era of Highly Active Antiretroviral Therapy. Clin Infect Dis 2011; 52:378.
- Opravil M, Pechère M, Speich R, et al. HIV-associated primary pulmonary hypertension. A case control study. Swiss HIV Cohort Study. Am J Respir Crit Care Med 1997; 155:990.
- Petitpretz P, Brenot F, Azarian R, et al. Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension. Circulation 1994; 89:2722.
- Stricker H, Domenighetti G, Mombelli G. Prostacyclin for HIV-associated pulmonary hypertension. Ann Intern Med 1997; 127:1043.
- Aguilar RV, Farber HW. Epoprostenol (prostacyclin) therapy in HIV-associated pulmonary hypertension. Am J Respir Crit Care Med 2000; 162:1846.
- Farber HW. HIV-associated pulmonary hypertension. AIDS Clin Care 2001; 13:53.
- Cea-Calvo L, Escribano Subías P, Tello de Menesses R, et al. [Treatment of HIV-associated pulmonary hypertension with treprostinil]. Rev Esp Cardiol 2003; 56:421.
- Ghofrani HA, Friese G, Discher T, et al. Inhaled iloprost is a potent acute pulmonary vasodilator in HIV-related severe pulmonary hypertension. Eur Respir J 2004; 23:321.
- Sitbon O, Gressin V, Speich R, et al. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med 2004; 170:1212.
- Degano B, Yaïci A, Le Pavec J, et al. Long-term effects of bosentan in patients with HIV-associated pulmonary arterial hypertension. Eur Respir J 2009; 33:92.
- Carlsen J, Kjeldsen K, Gerstoft J. Sildenafil as a successful treatment of otherwise fatal HIV-related pulmonary hypertension. AIDS 2002; 16:1568.
- Schumacher YO, Zdebik A, Huonker M, Kreisel W. Sildenafil in HIV-related pulmonary hypertension. AIDS 2001; 15:1747.
- Wong AR, Rasool AH, Abidin NZ, et al. Sildenafil as treatment for Human Immunodeficiency Virus-related pulmonary hypertension in a child. J Paediatr Child Health 2006; 42:147.
- Romanazzi S, Manes A, Hirani N, et al.. Sildenafil therapy for patients with pulmonary arterial hypertension associated with HIV infection. Am J Respir Crit Care Med 2007; :A1001.
- HIV-related factors
- Other viral factors
- Host factors
- CLINICAL PRESENTATION
- DIAGNOSTIC EVALUATION
- Confirm PAH
- Confirm HIV infection
- Exclude alternatives
- Calcium channel blockers
- Advanced therapy
- - Prostanoids
- - Endothelin receptor antagonists
- - Phosphodiesterase inhibitors
- - Guanylate cyclase stimulant
- SUMMARY AND RECOMMENDATIONS