Pulmonary hypertension associated with HIV infection: pulmonary vascular disease: the global perspective

Abstract

The success of antiretroviral therapies in improving the survival of patients infected with HIV and reducing HIV-associated opportunistic infections is undisputed. Nevertheless, long-term outcomes such as noninfectious cardiovascular complications, including cardiomegaly, pericarditis, myocarditis, and pulmonary arterial hypertension, are now serious concerns. The lung is a frequent target organ for disorders associated with HIV infection. HIV-related pulmonary arterial hypertension (HRPAH) affects more individuals who are infected with HIV than individuals who are uninfected. Moreover, the long-standing estimated prevalence of HRPAH in developed countries (calculated at 0.5%) is increasing as more clinician-scientists unify their efforts to screen patients who are pulmonary asymptomatic for pulmonary arterial hypertension. In order to decrease mortality, efforts are directed at early detection, diagnosis, and therapeutic interventions before the disease compromises patients' quality of life. This article reviews the logistics of screening approaches for HRPAH and discusses the substantial disease burden currently faced by developing countries, where the prevalence of HIV infection is higher and complicated by hyperendemic risk factors, limited access to antiretrovirals, and lack of screening tools. We also present mechanistic insights into HRPAH, including the role of HIV proteins and their potential use as screening tools, and, finally, areas that still need intense research.

Figure 1.

Phylogenetic reconstruction of HIV-1 negative factor (nef) sequences from a patient diagnosed with HIV-related pulmonary arterial hypertension (HRPAH). Archived peripheral blood mononuclear cells and lung tissue were obtained by echocardiography and enrolled in the Latium Registry of HRPAH in Rome. HIV nef was amplified using polymerase chain reaction, cloned, and sequenced; sequences were aligned using BioEdit (Ibis Therapeutics; Carlsbad, CA), and the phylogenetic tree was created using MEGA4 (The Biodesign Institute; Tempe, AZ). The analysis was statistically supported by 1,000 bootstrap resamplings, and only values > 70% are shown. Tissue-specific clustering of the nef quasi-species suggests differential evolution at the level of blood (●) and lung (○).

Figure 2.

Conceptual frame of PAH as a complication of HIV infection. The connections between hypothetical events contributing to HRPAH are indicated with black arrows. Therapeutic interventions are shown by the white block arrows. Areas that warrant further research to determine molecular mechanisms and potentially unravel future therapeutic targets are indicated by triangles. PAH = pulmonary arterial hypertension. See Figure 1 for expansion of the other abbreviation.