Relationship between endothelin-1 levels and pulmonary arterial hypertension in HIV-infected patients

Feijoo, Maribel Q.; Toro, Rocío; Torre, Mariola López Vazquez de la; Lennie, Vera; Arce, Cristina; Valencia, Eulalia; Vispo, Eugenia; Almerı́a, Carlos; Mangas, Alipio; Carbonero, Luz Martín

doi:10.1097/qad.0000000000000470

Cited by 12 publications

(10 citation statements)

References 37 publications

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“…Many factors, as viral proteins, HIV-related inflammation, coinfections with other microrganisms, and genetic susceptibility were considered to contribute to HIV-related PAH. Recently, a direct role of HIV infection to endothelial damage through the release of different inflammatory mediators such as endothelin-1 has been suggested [4]. Even the effect of antiretroviral therapy on pulmonary artery pressure has been an area of controversy.…”

Section: Discussionmentioning

confidence: 99%

Response to a Dolutegravir-based Regimen in an HIV-Infected Woman with Multiple Comorbidities and a Highly Resistant Strain

Capetti¹,

Carenzi²,

Astuti³

et al. 2015

AJMCR

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HIV-infected patients have a higher burden of comorbidities than the general population and drug-drug interactions limit the choice of antiretroviral compounds, also limiting the possibility of drug sequencing in case of toxicity or failure. In our patient, affected by HIV-related pulmonary hypertension (HIV-PAH), the use of sildenafil and ambrisentan excluded the possibility of using two of the main classes of antiretrovirals, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Having failed a combination regimen based on raltegravir, while awaiting the results of genotypic testing for drug resistance she was switched to dolutegravir, a brand new integrase strand transfer inhibitor (INSTI) with high genetic barrier, and in one month her HIV-1 viremia dramatically dropped to undetectable levels. The genotypic test revealed resistance to all the drugs she was taking including dolutegravir. The backbone was changed to a dual regimen including rilpivirine and viral suppression was maintained at three months. Unprecedented pharmacokinetic data are provided for the two antiviral drugs in combination with sildenafil and ambrisentan.

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Section: Discussionmentioning

confidence: 99%

Response to a Dolutegravir-based Regimen in an HIV-Infected Woman with Multiple Comorbidities and a Highly Resistant Strain

Capetti¹,

Carenzi²,

Astuti³

et al. 2015

AJMCR

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“…gp120 also increases secretion of another important PAH factor, endothelin-1 (88). Endothelin-1 levels are higher in HIV-seropositive individuals and correlate with HIV-PAH severity (89). …”

Section: Pathogenesis Of Hiv-pahmentioning

confidence: 99%

Maintaining lung health with longstanding HIV

Collini

Morris

2016

Current Opinion in Infectious Diseases

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Purpose of review Human immunodeficiency virus (HIV) is now managed as a chronic disease. Non-infectious pulmonary conditions have replaced infection as the biggest threat to lung health, particularly as HIV cohorts age, but there is no consensus on how best to maintain long-term lung health. We review the epidemiology and pathogenesis of chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH) and lung cancer in HIV-seropositive individuals. Recent Findings Diagnoses of COPD are now up to 50% more prevalent in HIV-seropositive individuals than HIV-uninfected controls, and prospective pulmonary function studies find significant impairment in 7%–>50% of HIV-seropositive individuals. The prevalence of HIV-PAH is 0.2%–0.5%, and lung cancer is 2–3 times more prevalent in HIV-seropositive individuals. Although host factors such as age and smoking have a role, HIV is an independent contributor to the pathogenesis of COPD, PAH and lung cancer. Chronic inflammation, immune senescence, oxidative stress and direct effects of viral proteins are all potential pathogenetic mechanisms. Despite their prevalence, non-infectious lung diseases remain under-recognized and evidence for effective screening strategies in HIV-seropositive individuals is limited. Summary COPD, PAH and lung cancer are a growing threat to lung health in the HAART era necessitating early recognition.

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“…49 A case-control study showed that plasma endothelin-1 levels were elevated in HIV-infected patients and were most elevated in patients with severe HIV-PAH. 50 Both HIV Env and Tat have been shown in vitro to enhance TNF-α-mediated activation of lung microvascular endothelial cells. 51 Mermis and colleagues identified increased expression of hypoxia-inducible factor-1α (HIF-1α) and PDGF-BB in the HIV transgenic rat, and showed in vitro that endothelial cells stimulated with HIV-Env increase PDGF-BB expression, which is abrogated by siRNA blockade of HIF-1α.…”

Section: Direct Effects Of Hiv Viral Proteinsmentioning

confidence: 99%

Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection

George

Singh

Gladwin

2016

Semin Respir Crit Care Med

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The goal of this review is to describe evolving epidemiology of noninfectious, nonneoplastic pulmonary complications of HIV infection, including HIV-associated pulmonary arterial hypertension (HIV-PAH) and interstitial lung disease (ILD). The development of antiretroviral therapy has rendered HIV a chronic illness in treated patients, and the landscape of HIV-associated medical conditions continues to evolve. Although there has been a shift away from AIDS-defining infectious diseases and malignancies, HIV-PAH continues to affect survival adversely when compared with HIV-infected patients without PAH. Studies of pre- and post-highly active antiretroviral therapy (HAART) era show that the prevalence of HIV-PAH remains high and unchanged. The increased prevalence of PAH among HIV-infected individuals has led to several complementary theories about potential mechanisms underlying this disease. Unique mechanisms of HIV-PAH focus on direct effects of viral proteins; alterations in cellular immunologic/inflammatory reactions to the virus; additive effects of cocaine, heroin, and other drugs of abuse; and potentially toxic aspects of antiretroviral and associated therapies. PAH-specific therapy with HAART is likely beneficial in the treatment of HIV-PAH patients. The prevalence of ILD in HIV-infected individuals is also significantly higher than that in the general population. Lymphoid interstitial pneumonitis (LIP) and nonspecific interstitial pneumonia (NSIP) have been reported in both HIV-infected children and adults, and NSIP is more common than LIP in HIV-infected patients. At present, there is no consensus on the pathogenesis of LIP and NSIP in HIV. Finally, we briefly review the literature on venous thromboembolic disease in HIV-infected individuals.

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Relationship between endothelin-1 levels and pulmonary arterial hypertension in HIV-infected patients

Abstract: Plasma endothelin-1 levels are higher in HIV patients with PAH than in the HIV-noninfected population and levels increase with the severity of the PAH.

Cited by 12 publications

References 37 publications

Response to a Dolutegravir-based Regimen in an HIV-Infected Woman with Multiple Comorbidities and a Highly Resistant Strain

Response to a Dolutegravir-based Regimen in an HIV-Infected Woman with Multiple Comorbidities and a Highly Resistant Strain

Maintaining lung health with longstanding HIV

Noninfectious and Nonneoplastic Conditions Associated with Human Immunodeficiency Virus Infection

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