Role of Human Immunodeficiency Virus in Primary Pulmonary Hypertension

Abstract

Previous cases of pulmonary hypertension (PH) in human immunodeficiency virus (HIV) infection have been reported in the literature. The role of HIV in PH is still debatable. The purpose of this report was to analyze whether HIV plays a direct or indirect role in PH pathogenesis. Between February and November 1997, 56 HIV-infected patients with cardiac symptoms and signs were studied by serial color Doppler echocardiography. In four patients (7.1%), PH not related to other well-known associated conditions, was disclosed. In spite of a low serum HIV RNA viral load and a high-efficacy antiretroviral therapy, including a protease inhibitor in two patients, PH developed and worsened. It could be hypothesized that in some patients with an individual immunogenetic predisposition, a high secretion of cytokines and endothelin-1 stimulated by an unidentified pathogen different from HIV could lead to PH. Antiretroviral therapy seems not to prevent or reduce right ventricle pressure gradient in PH.

Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension

“…This indicated that some standard antiretroviral therapy, in particular firstgeneration HIV protease inhibitors but also some HAART treatment, may facilitate the pulmonary vascular pathophenotype of HIV-associated PAH. 103 The mechanism underlying the relationship between ritonavir and pulmonary hypertension is incompletely characterized; however, ritonavir inhibits bradkykinin-dependent vasorelaxation in a concentration-dependent manner leading to endothelial dysfunction. 102 In fact, 5 HAART drugs (ritonavir, indinavir, lamivudine, abacavir, and zidovudine) have been shown to decrease endothelial nitric oxide synthase expression significantly and increase reactive oxygen species levels and ERK1/2 activation in human pulmonary artery endothelial cells in vitro.…”

Patología cardiovascular en pacientes con infección por el virus de inmunodeficiencia humana

“…De todos modos, es importante señalar que los pacientes con hipertensión pulmonar asociada a la infección por el VIH tienen un tiempo de supervivencia menor en comparación con aquellos que no tienen esta condición (1,3 años versus 2,6 años) (2,8.9) . Se ha estimado que ocurre en casi el 0,5% de pacientes hospitalizados y es una causa de compromiso cardíaco severo con cor pulmonale y muerte asociados (2,(8)(9)(10) .…”

Manifestações cardiovasculares em pacientes com infecção pelo vírus da imunodeficiência humana

“…Its prevalence is 1/200 cases, compared with 1/ 200,000 cases in the general population [46][47][48][49][50] . Its detection is often associated with pulmonary infections, use of intravenous drugs, transfusion of factor VIII to hemophilic patients, venous thromboembolism, heart failure and the presence of HLA-DR6 and HLA-DR52 46,47 . It affects approximately 0.5% of hospitalized patients with AIDS.…”

“…It is suggested that HIV itself causes endothelial injury and release of vasoconstrictive mediators such as endothelin-1, interleukin-6 (IL-6), and the tumor necrosis factor alpha in the pulmonary arteries. HIV is often identified in the alveolar macrophages in histological tets 47 . These macrophages release TNF-α, free radicals and proteolytic enzymes in response to the infection.…”

“…Lymphokines also seem to contribute to the endothelial proliferation observed in pulmonary hypertension since they promote leukocyte adhesion in the endothelium. Activation of α-1 adrenergic receptors and genetic factors (increased frequency of HLA-DR 6 and DR 52) have also been related to its pathogenesis 47,50 .…”