RARE DISEASE
Pulmonary arterial hypertension associated with HIV infection
Pulmonary arterial hypertension associated with HIV infection
Pulmonary arterial hypertension associated with HIV infection
Synonyms: PAH associated with HIV infaction
Synonyms: PAH associated with HIV infaction
Synonyms: PAH associated with HIV infaction
Drug discovery
0
drugs
With orphan designations
Overview
Pulmonary arterial hypertension (PAH) associated with HIV infection is a severe vascular complication characterized by pulmonary vascular remodeling and elevated pulmonary artery pressure. It occurs 2500 times more frequently in HIV patients than the general population, with an estimated global prevalence of 0.4-5% [1][6][16]. Pathogenesis involves HIV proteins (Nef, Tat, gp120), chronic inflammation, and comorbidities rather than direct viral infection [1][9][15]. Diagnosis requires right heart catheterization after echocardiographic screening [9][16]. Prognosis remains poor without treatment, but combination antiretroviral therapy (ART) and PAH-specific therapies improve survival [3][11][19].
Burden
Accounts for 5-10% of HIV-related deaths from right heart failure [1][9][16]
Patients demonstrate worse hemodynamics (higher pulmonary vascular resistance) than idiopathic PAH despite younger age [5][19]
Management complexity increased by renal dysfunction (23% prevalence) and ART-PAH drug interactions [5][14]
Therapies
ART foundation: Essential for HIV control, though direct PAH benefits remain unclear [3][13][19]
PAH-targeted therapies: Endothelin receptor antagonists (bosentan), PDE5 inhibitors (sildenafil/tadalafil), and prostacyclins, with careful monitoring for drug interactions with ART [3][11][14]
Combination therapy: Considered for severe cases, though evidence remains limited compared to idiopathic PAH [3][14][19]
Categories: rare respiratory diseases, rare transplant-related disorders
Research Papers
60 drug discovery papers about Pulmonary arterial hypertension associated with HIV infection. Recent publications:
60 drug discovery papers about Pulmonary arterial hypertension associated with HIV infection. Recent publications:
categories:
Small molecules
small molecules
2026-06-26 | Pulmonary Immune Cell Landscape Altered by Exposure to HIV, Schistosoma and Their Combination.
Local immune cell activation and vascular remodelling are characteristic pathogenic features of pulmonary arterial hypertension (PAH). HIV and schistosome infections have been individually associated with PAH. However, whether co-infection with these pathogens has a distinct impact on the development of pulmonary vascular disease remains poorly understood, partly due to the lack of experimental animal models. In a novel non-infectious model of HIV and Schistosoma pulmonary co-exposure based on lung embolisation of S. mansoni eggs in HIV-transgenic (HIV) mice, we previously reported exacerbated endothelial remodelling and dysfunction, along with increased pulmonary arterial pressure; which were associated with a unique profile of pro-inflammatory cytokines in the lung. In the present study, we used flow cytometric analysis of isolated lung leukocytes and immunofluorescence staining to characterise the pulmonary immune cell landscape associated with individual or combined exposure to HIV and schistosome. Compared with mice exposed to HIV (untreated HIV mice) or schistosome (egg-treated wild-type mice), co-exposed (egg-treated HIV mice) animals showed significantly increased numbers of interstitial and alveolar macrophages, patrolling-type monocytes, NKT and γδ T cells, and reduced CD8+ αβ T cells. Other lung immune cells, including inflammatory-type monocytes, eosinophils/neutrophils, dendritic cells, CD4+ αβ T cells, NK cells and B cells were not significantly affected in the co-exposure condition. Taken together, these results show for the first time that combined pulmonary exposure to HIV and Schistosoma, as it may occur in co-infected individuals, alters the local immune cell landscape in a manner distinct from that of individual exposure. Furthermore, these findings may contribute to a better understanding of the complex inflammatory processes involved in the pathogenesis of PAH, thereby supporting the development of therapies targeting pathogenic immune cells in pulmonary vascular disease associated with HIV and Schistosoma co-morbidity.
2026-06-26 | Molecular-Genetic Basis of Pulmonary Arterial Hypertension (PAH).
Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20-30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional "second hits", including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53-86% of heritable PAH and 14-35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH.
2026-01-26 | Characteristics of pulmonary arterial hypertension course in a female patient with HIV infection. A case report
Introduction . The development of pulmonary arterial hypertension (PAH) worsens the HIV infection course, patient’s condition and increases the risk of mortality. Timely initiation of antiretroviral therapy (ART), appropriate selection of specific PAH therapy, and follow-up predictably improve the prognosis of these patients. Brief description . This case report describes the characteristics of the disease onset and the nature of cardiac remodeling in a female patient with newly diagnosed HIV infection-associated PAH. The patient’s complex presentation at the time of diagnosis included not only HIV infection without ART, but also severe right ventricular dysfunction and remodeling with excessive trabeculation and signs of myocardial noncompaction, mildly reduced left ventricular systolic function, elevated transaminases and total blood protein due to the gamma globulin fraction, iron deficiency anemia, and a history of smoking. Given the ambiguous disease presentation, sildenafil monotherapy was chosen as initial PAH-specific therapy. With the initiation of sildenafil and ART, the patient achieved a low risk of mortality, maintained compensated underlying disease, and regression of PAH after two years of follow-up. Discussion . In the absence of ART and with progressive PAH, the patient developed severe right ventricular dysfunction and excessive trabeculation. Despite the high mortality risk at the time of diagnosis verification, sildenafil monotherapy was prescribed based on the patient’s comorbidities (elevated transaminases, decreased left ventricular ejection fraction in history), as well as the proven precapillary contribution to pulmonary hypertension. The key to the favorable course and regression of PAH in this patient was the timely initiation of ART and PAH-specific therapy with continued good medication adherence, as well as regular follow-up.
2026-01-26 | Successful treatment of a patient with left main coronary artery compression due to pulmonary arterial hypertension in HIV infection: a case report
Human immunodeficiency virus (HIV) is characterized by slow and gradual damage to the immune system. In recent years, its incidence has increased by an average of 10% per year. However, in the era of antiretroviral therapy, the life expectancy of this cohort of patients has increased, shifting the focus to complications, including cardiovascular ones. This article describes a patient with pulmonary arterial hypertension (PAH) associated with HIV infection who developed a rare, severe complication — left main coronary artery compression syndrome due to a dilated pulmonary artery. It describes successful endovascular treatment and the selection of PAH-specific therapy.
2025-11-01 | Pulmonary arterial hypertension associated with toxic rapeseed oil: a continuous disease?
Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension (PH), defined by right heart catheterisation as a mean pulmonary arterial pressure greater than 20 mmHg, pulmonary vascular resistance greater than two Wood units, and pulmonary arterial wedge pressure less than 15 mmHg [1, 2]. Beyond idiopathic and heritable forms, PAH can be associated with various conditions – mainly connective tissue disorders, HIV infection, or portal hypertension – but also with exposure to drugs and toxins [1, 2]. The history of drug- and toxin-induced PAH is linked to several health scandals, including those involving aminorex and fenfluramine derivatives [3, 4].
cell therapies
2024-09-28 | Unraveling the pathogenesis of viral-induced pulmonary arterial hypertension: Possible new therapeutic avenues with mesenchymal stromal cells and their derivatives.
Pulmonary hypertension (PH) is a severe condition characterized by elevated pressure in the pulmonary artery, where metabolic and mitochondrial dysfunction may contribute to its progression. Within the PH spectrum, pulmonary arterial hypertension (PAH) stands out with its primary pulmonary vasculopathy. PAH's prevalence varies from 0.4 to 1.4 per 100,000 individuals and is associated with diverse conditions, including viral infections such as HIV. Notably, recent observations highlight an increased occurrence of PAH among COVID-19 patients, even in the absence of pre-existing cardiopulmonary disorders. While current treatments offer partial relief, there's a pressing need for innovative therapeutic strategies, among which mesenchymal stromal cells (MSCs) and their derivatives hold promise. This review critically evaluates recent investigations into viral-induced PAH, encompassing pathogens like human immunodeficiency virus, herpesvirus, Cytomegalovirus, Hepatitis B and C viruses, SARS-CoV-2, and Human endogenous retrovirus K (HERKV), with a specific emphasis on mitochondrial dysfunction. Furthermore, we explore the underlying rationale driving novel therapeutic modalities, including MSCs, extracellular vesicles, and mitochondrial interventions, within the framework of PAH management.
small molecules
2026-06-26 | Pulmonary Immune Cell Landscape Altered by Exposure to HIV, Schistosoma and Their Combination.
Local immune cell activation and vascular remodelling are characteristic pathogenic features of pulmonary arterial hypertension (PAH). HIV and schistosome infections have been individually associated with PAH. However, whether co-infection with these pathogens has a distinct impact on the development of pulmonary vascular disease remains poorly understood, partly due to the lack of experimental animal models. In a novel non-infectious model of HIV and Schistosoma pulmonary co-exposure based on lung embolisation of S. mansoni eggs in HIV-transgenic (HIV) mice, we previously reported exacerbated endothelial remodelling and dysfunction, along with increased pulmonary arterial pressure; which were associated with a unique profile of pro-inflammatory cytokines in the lung. In the present study, we used flow cytometric analysis of isolated lung leukocytes and immunofluorescence staining to characterise the pulmonary immune cell landscape associated with individual or combined exposure to HIV and schistosome. Compared with mice exposed to HIV (untreated HIV mice) or schistosome (egg-treated wild-type mice), co-exposed (egg-treated HIV mice) animals showed significantly increased numbers of interstitial and alveolar macrophages, patrolling-type monocytes, NKT and γδ T cells, and reduced CD8+ αβ T cells. Other lung immune cells, including inflammatory-type monocytes, eosinophils/neutrophils, dendritic cells, CD4+ αβ T cells, NK cells and B cells were not significantly affected in the co-exposure condition. Taken together, these results show for the first time that combined pulmonary exposure to HIV and Schistosoma, as it may occur in co-infected individuals, alters the local immune cell landscape in a manner distinct from that of individual exposure. Furthermore, these findings may contribute to a better understanding of the complex inflammatory processes involved in the pathogenesis of PAH, thereby supporting the development of therapies targeting pathogenic immune cells in pulmonary vascular disease associated with HIV and Schistosoma co-morbidity.
2026-06-26 | Molecular-Genetic Basis of Pulmonary Arterial Hypertension (PAH).
Pulmonary arterial hypertension (PAH) is a progressive, fatal disease of the pulmonary vasculature characterized by obliterative remodeling of small pulmonary arteries, leading to sustained elevation of pulmonary vascular resistance, right ventricular failure, and premature death. The diagnostic gold standard remains right heart catheterization, requiring a mean pulmonary artery pressure greater than 20 mmHg at rest, a pulmonary arterial wedge pressure of 15 mmHg or below, and a pulmonary vascular resistance exceeding 2 Wood units. PAH is an autosomal dominant disorder with markedly incomplete penetrance of approximately 20-30%, indicating that germline mutations alone are insufficient to cause disease. Disease manifestation requires additional "second hits", including chronic hypoxia, systemic inflammation, hemodynamic stress, hormonal influences, and common genetic modifiers such as single-nucleotide polymorphisms (SNPs). This genetic and environmental complexity underpins the broad clinical heterogeneity observed across PAH subtypes, which include idiopathic PAH, heritable PAH, and disease associated with connective tissue disorders, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and drug or toxin exposure. This review provides a comprehensive and critical appraisal of the molecular-genetic architecture of PAH. Thirty genes have now been implicated in disease pathogenesis, spanning seven functional categories: receptors of the TGF-β/BMP signaling family (BMPR2, ACVRL1, ENG, BMPR1B); circulating BMP ligands (GDF2, BMP10); transcription factors (TBX4, SOX17, KLF4, FOXF1, SMAD1, SMAD4, SMAD9); membrane and polyamine transporters (ATP13A3, AQP1); potassium channel regulators (KCNA5, KCNK3, ABCC8); metabolic and mitochondrial genes (EIF2AK4, NFU1, GGCX); signaling receptors and structural proteins (NOTCH3, KDR, CAV1, PLEKHH2); vasoactive and extracellular matrix regulators (KLK1, CBLN2, CD248); and epigenetic regulators (TET2, TOPBP1). Among these, BMPR2 is the dominant contributor, accounting for 53-86% of heritable PAH and 14-35% of idiopathic cases. The remaining genes each account for fewer than 5% of cases individually, collectively reflecting a broad landscape of rare and ultra-rare genetic contributions. For each gene, we critically evaluate the strength of genetic evidence, pathogenic mechanisms, degree of mechanistic resolution, and clinical relevance. We further discuss the contribution of emerging technologies, including whole-genome sequencing, single-cell and spatial transcriptomics, multi-omics integration, iPSC-derived vascular models, and artificial intelligence, to expanding the PAH genetic architecture beyond single-gene discovery. A key theme across this landscape is convergence: despite mechanistic diversity at the gene level, most PAH-associated variants ultimately impair endothelial quiescence, promote smooth muscle proliferation, and drive apoptosis resistance through disruption of BMP signaling amplitude, transcriptional stability, ion channel homeostasis, metabolic integrity, or epigenetic regulation. This convergence supports both a unified therapeutic rationale and a precision medicine framework for genotype-stratified intervention in PAH.
2026-01-26 | Characteristics of pulmonary arterial hypertension course in a female patient with HIV infection. A case report
Introduction . The development of pulmonary arterial hypertension (PAH) worsens the HIV infection course, patient’s condition and increases the risk of mortality. Timely initiation of antiretroviral therapy (ART), appropriate selection of specific PAH therapy, and follow-up predictably improve the prognosis of these patients. Brief description . This case report describes the characteristics of the disease onset and the nature of cardiac remodeling in a female patient with newly diagnosed HIV infection-associated PAH. The patient’s complex presentation at the time of diagnosis included not only HIV infection without ART, but also severe right ventricular dysfunction and remodeling with excessive trabeculation and signs of myocardial noncompaction, mildly reduced left ventricular systolic function, elevated transaminases and total blood protein due to the gamma globulin fraction, iron deficiency anemia, and a history of smoking. Given the ambiguous disease presentation, sildenafil monotherapy was chosen as initial PAH-specific therapy. With the initiation of sildenafil and ART, the patient achieved a low risk of mortality, maintained compensated underlying disease, and regression of PAH after two years of follow-up. Discussion . In the absence of ART and with progressive PAH, the patient developed severe right ventricular dysfunction and excessive trabeculation. Despite the high mortality risk at the time of diagnosis verification, sildenafil monotherapy was prescribed based on the patient’s comorbidities (elevated transaminases, decreased left ventricular ejection fraction in history), as well as the proven precapillary contribution to pulmonary hypertension. The key to the favorable course and regression of PAH in this patient was the timely initiation of ART and PAH-specific therapy with continued good medication adherence, as well as regular follow-up.
2026-01-26 | Successful treatment of a patient with left main coronary artery compression due to pulmonary arterial hypertension in HIV infection: a case report
Human immunodeficiency virus (HIV) is characterized by slow and gradual damage to the immune system. In recent years, its incidence has increased by an average of 10% per year. However, in the era of antiretroviral therapy, the life expectancy of this cohort of patients has increased, shifting the focus to complications, including cardiovascular ones. This article describes a patient with pulmonary arterial hypertension (PAH) associated with HIV infection who developed a rare, severe complication — left main coronary artery compression syndrome due to a dilated pulmonary artery. It describes successful endovascular treatment and the selection of PAH-specific therapy.
2025-11-01 | Pulmonary arterial hypertension associated with toxic rapeseed oil: a continuous disease?
Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension (PH), defined by right heart catheterisation as a mean pulmonary arterial pressure greater than 20 mmHg, pulmonary vascular resistance greater than two Wood units, and pulmonary arterial wedge pressure less than 15 mmHg [1, 2]. Beyond idiopathic and heritable forms, PAH can be associated with various conditions – mainly connective tissue disorders, HIV infection, or portal hypertension – but also with exposure to drugs and toxins [1, 2]. The history of drug- and toxin-induced PAH is linked to several health scandals, including those involving aminorex and fenfluramine derivatives [3, 4].
cell therapies
2024-09-28 | Unraveling the pathogenesis of viral-induced pulmonary arterial hypertension: Possible new therapeutic avenues with mesenchymal stromal cells and their derivatives.
Pulmonary hypertension (PH) is a severe condition characterized by elevated pressure in the pulmonary artery, where metabolic and mitochondrial dysfunction may contribute to its progression. Within the PH spectrum, pulmonary arterial hypertension (PAH) stands out with its primary pulmonary vasculopathy. PAH's prevalence varies from 0.4 to 1.4 per 100,000 individuals and is associated with diverse conditions, including viral infections such as HIV. Notably, recent observations highlight an increased occurrence of PAH among COVID-19 patients, even in the absence of pre-existing cardiopulmonary disorders. While current treatments offer partial relief, there's a pressing need for innovative therapeutic strategies, among which mesenchymal stromal cells (MSCs) and their derivatives hold promise. This review critically evaluates recent investigations into viral-induced PAH, encompassing pathogens like human immunodeficiency virus, herpesvirus, Cytomegalovirus, Hepatitis B and C viruses, SARS-CoV-2, and Human endogenous retrovirus K (HERKV), with a specific emphasis on mitochondrial dysfunction. Furthermore, we explore the underlying rationale driving novel therapeutic modalities, including MSCs, extracellular vesicles, and mitochondrial interventions, within the framework of PAH management.
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