Drug abuse and HIV-related pulmonary hypertension: double hit injury

Abstract

: Improved survival among HIV-1-infected individuals with the advent of antiretroviral therapy has clearly led to a greater prevalence of noninfectious complications. One of the most devastating sequelae in these individuals is the development of pulmonary arterial hypertension (PAH). Various epidemiological studies suggest worse survival of HIV-PAH patients when compared with other forms of PAH. Given that only a subset and not all HIV-infected individuals develop HIV-PAH, it is suggested that an additional second-hit of genetic or environmental trigger 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, and the like, 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.

Figure 1:

Outline of the suggested mechanisms involved in the HIV-proteins and drugs of abuse mediated endothelial dysfunction.

Figure 2:

Schematic representation of signaling mechanisms that mediate the pulmonary smooth muscle proliferation in response to dual hit of HIV-infection/viral proteins and cocaine.

Figure 3:

Significant increase in the expression of TN-C in the human pulmonary arterial smooth muscle cells on exposure to HIV-protein(s) and cocaine. Western blot (A) and densitometry analysis (B) of total lung extracts; and immunohistochemical staining of lung sections (C) from HIV-infected and /or IVDUs; TN-C mRNA (D) and protein expression (E-F) in the human primary PASMCs on treatment with cocaine and/or HIV-Tat.