Human Immunodeficiency Virus and Heart Failure in Low- and Middle-Income Countries

Abstract

Successful combination therapy for human immunodeficiency virus (HIV) has transformed this disease from a short-lived infection with high mortality to a chronic disease associated with increasing life expectancy. This is true for high- as well as low- and middle-income countries. As a result of this increased life expectancy, people living with HIV are now at risk of developing other chronic diseases associated with aging. Heart failure has been common among people living with HIV in the eras of pre- and post- availability of antiretroviral therapy; however, our current understanding of the pathogenesis and approaches to management have not been systematically addressed. HIV may cause heart failure through direct (e.g., viral replication, mitochondrial dysfunction, cardiac autoimmunity, autonomic dysfunction) and indirect (e.g., opportunistic infections, antiretroviral therapy, alcohol abuse, micronutrient deficiency, tobacco use) pathways. In low- and middle-income countries, 2 large observational studies have recently reported clinical characteristics and outcomes in these patients. HIV-associated heart failure remains a common cardiac diagnosis in people living with heart failure, yet a unifying set of diagnostic criteria is lacking. Treatment patterns for heart failure fall short of society guidelines. Although there may be promise in cardiac glycosides for treating heart failure in people living with HIV, clinical studies are needed to validate in vitro findings. Owing to the burden of HIV in low- and middle-income countries and the concurrent rise of traditional cardiovascular risk factors, strategic and concerted efforts in this area are likely to impact the care of people living with HIV around the globe.

Keywords: developing countries; heart failure; human immunodeficiency virus.

Figure 1. Worldwide Distribution of Studies of HF and Burden of HIV

Country-level data for (A) the number of individuals included in clinical studies and registries for HF, and (B) the number of adults living with HIV Data from the World Health Organization Global Health Observatory Data Repository; U.S. Central Intelligence Agenct World Factbook, and the Centers for Disaese Control, Taiwan (ROC). (14,22-25,99-101). HF = heart failure; HIV = human immunodeficiency virus.

Figure 2. Pathways of HIV-Associated HF

HIV may cause HF through direct and indirect pathways. Direct pathways involve HIV viral replication, an autoimmune milieu, and autonomic dysfunction. Viral replication also affects mitochondrial function, which is associated with cardiac myocyte dysfunction. Indirect pathways leading to HF include factors that are common among PLHIV such as opportunistic infections, antiretroviral therapy, alcohol (EtOH) abuse, micronutrient deficiency, and tobacco use. HF = heart failure; HIV = human immunodeficiency virus; PLHIV = people living with HIV.

Figure 3. Myocardial Deformation Tracings in HIV-Infected Individuals With Normal LVEF

(A) Normal global longitudinal strain (GLS) pattern in asymptomatic PLHIV (average GLS = −19%). (B) Abnormal GLS pattern in asymptomatic PLHIV (average GLS = −6%). (Illustrations courtesy of Duke University Medical Center Cardiac Diagnostic Unit.) HIV = human immunodeficiency virus; LVEF = left ventricular ejection fraction; PLHIV = people living with HIV.

Central Illustration. Current Knowledge, Knowledge Gaps, and Future Research

Directions for HIV-associated heart failure in low- and middle-income countries. HIV = human immunodeficiency virus.