Drug abuse and HIV-related pulmonary hypertension

Abstract

Improved survival among HIV-1 infected individuals with the advent of antiretroviral therapy has clearly led to a greater prevalence of non-infectious complications. One of the most devastating sequelae in these individuals is the development of pulmonary arterial hypertension (PAH). Various epidemiological studies suggest a worse survival of HIV-PAH patients when compared to other forms of PAH. Given that only a subset and not all HIV-infected individuals develop HIV-PAH, suggests that an additional second hit of genetic or environmental triggers is needed for the development of PAH. In this context, it has been well documented that HIV patients who abuse illicit drugs such as stimulants, opioids etc. are more susceptible to develop PAH. In this review, we highlight the studies that support the significance of a double hit of HIV and drug abuse in the incidence of PAH and focus on the research that has been undertaken to unravel the pathobiology and vascular remodeling mechanisms underlying the deleterious synergy between HIV infection and drugs of abuse in orchestrating the development of PAH.

Sugen–morphine model of pulmonary arterial hypertension

“…11 However, a recent study suggests that pulmonary EC injury alone is insufficient to cause severe PAH, thus highlighting the requirement of additional factors in the development of PAH 12 and importance of a ''double-hit or multiple hits'' mechanism that also applies to PAH animal models. 2,[13][14][15][16] Similar to the injurious effects of SU5416 on pulmonary ECs, morphine has been shown to cause both apoptosis and proliferation of vascular ECs. [17][18][19] We previously reported that the combination of morphine with HIV-infection accentuates pulmonary vascular remodeling characterized by formation of neointimal fibrotic or plexiform lesions in Simian Immunodeficiency Virus (SIV)-infected Rhesus macaques.…”

“…11 However, a recent study suggests that pulmonary EC injury alone is insufficient to cause severe PAH, thus highlighting the requirement of additional factors in the development of PAH 12 and importance of a “double-hit or multiple hits” mechanism that also applies to PAH animal models. 2,13–16…”

“…Pulmonary arterial hypertension (PAH), Group 1 of the pulmonary hypertension (PH) classification, comprises multiple etiologies such as drug‐induced PAH 1 and HIV‐related PAH, 2 as well as hereditary (e.g. Bone Morphogenetic Protein Receptor II) and idiopathic forms 3 .…”

“…It has been well established that SU5416 primarily causes initial endothelial cell (EC) injury and later hyperproliferation of apoptosis‐resistant ECs, 11 a characteristic of angio‐obliterative (plexiform/complex) lesion formation in the development of severe PAH 11 . However, a recent study suggests that pulmonary EC injury alone is insufficient to cause severe PAH, thus highlighting the requirement of additional factors in the development of PAH 12 and importance of a “double‐hit or multiple hits” mechanism that also applies to PAH animal models 2 , 13–16 …”

TGF-β1 in extracellular vesicles from HIV-infected plasma and macrophages linked to cardiopulmonary dysfunction

“…Pulmonary arterial hypertension (PAH) is one of the most devastating non-infectious complications related to HIV infection and echocardiographic evidences suggest prevalence of increased pulmonary artery systolic pressure (PASP) in 2.6-15.5% of people living with HIV (PLWH) (1), (2). HIV-associated PAH falls under Group I pulmonary hypertension (PH) and the risk factors such as cocaine, methamphetamine and intravenous drug use (IVDU) in PLWH can potentiate the development of HIV-PAH (2)(3)(4). Furthermore, with the increasing burden of cardiac and chronic respiratory complications in PLWH, the prevalence of secondary PH is suggested to increase as well, in these individuals (5,6).…”