Review ArticleEndothelial and platelet function alterations in HIV-infected patients
Introduction
Since the first identification of acquired immune deficiency syndrome (AIDS), in the summer of 1981, HIV infection has spread in successive waves in various regions around the globe.
At the end of 1998, there were more than 23 million people with HIV infection or AIDS, 43 percent of them female, according to estimates by the Joint United Nations Programme on HIV/AIDS (UNAIDS). An estimated 3.2 million new HIV infections occurred worldwide during 1998, approximately 16,000 each day. More than 95 percent of these new infections occurred in developing countries. In the 90's HIV infection was the fourth leading cause of death worldwide, resulting in an estimated 2.3 million deaths for year. In 2009, the most recent year for which epidemiologic data are available, an estimated 33.3 million people worldwide were HIV-positive (Table 1) [1]. Twenty million more people are predicted to acquire HIV by 2031 [2].
Although the epidemic is still taking a staggering toll, progress in HIV research has been extraordinary. The identification of HIV as the causative agent of AIDS led to intense activity in the field of molecular virology, with the characterization of three structural and six regulatory genes and of their relationships with the complex mechanisms of HIV replication. HIV enters the body and binds to dendritic cells which carry the virus to CD4+ T cells. Infected CD4+ T cells home to lymphoid tissue where the infection is established. Virus replication accelerates, and massive viremia leads to the dissemination of the virus throughout the body's lymphoid tissue. An HIV-specific immune response occurs and virus is trapped on the follicular dendritic cells of germinal centers in lymphoid tissue. At this point, chronic, persistent infection is established despite immunological response to the virus. Immune activation is an important driver of HIV replication and is mediated by the secretion of various cytokines and by aberrant cell-signaling caused by interaction of the viral envelope with cellular receptors [3].
Based on the acquired molecular knowledge, the development of novel antiretroviral therapy (HAART), with 6.6 million people HIV now on treatment, has saved the life of many people. While before the era of HAART the estimated median survival for a young person infected with HIV was 7 years, currently it reaches about 35 years. The introduction of HAART has thus significantly improved the prognosis of HIV-infected patients with a dramatic reduction in both morbidity and mortality and an improvement in patients' quality of life. However, complications involving the cardiovascular system, previously not manifested, have emerged.
Section snippets
HIV infection and cardiovascular risk
Several clinical studies have suggested that HIV-infected patients have unexpectedly high rates of ischemic cardiovascular events, in particular coronary heart disease (CHD) and myocardial infarction. Klein et al. found that HIV-positive members of the Northern California Kaiser Permanente Medical Care Program, a large health maintenance organization, had a significantly higher rate of hospitalization for coronary heart disease and myocardial infarction than HIV-negative members [4]. Currier et
Interaction of endothelial cells with HIV
Endothelial dysfunction is thought to be a major link between infection, inflammation, and atherosclerosis [25] and the HIV epidemic introduced a new agent associated with endothelial dysfunction [26].
HIV can infect endothelial cells thus activating them. Entry of the virus into endothelial cells may occur in different ways, such as through CD4 antigen, galactosyl-ceramide receptors, or chemokine receptors (CCR3 and CXCR4) [26], and indeed HIV-infected individuals show a marked depletion of
HIV and platelets
Hemostasis is a critical process finalized to seal breaches in the vascular system. This serves two functions: prevention of further blood loss, and denial of access for pathogens to the vascular system. Platelets are key mediators of this response, and act to stop the leak and facilitate wound healing. In addition, platelets play a key role in preventing infection and participate in the immune response.
Several studies have shown that platelets are rapidly deployed to sites of infection and
Conclusions
Besides its effects on the immune system, HIV virus has multiple and complex interactions with the endothelium and with platelets. After the introduction of HAART chronic HIV-infection has become a condition of accelerated atherosclerosis and high cardiovascular risk. HIV-virus has activating effects on the endothelium and platelets and these may in part contribute to the cardiovascular complications of HIV-infection. Moreover, some specific components of HAART, like ABC, enhancing
Acknowledgment
This work was supported in part by research grants from Fondazione Cassa di Risparmio di Perugia (protocol n. 2011.0317.021), a grant from the Italian Ministry of Health-AIDS (n. RF-UPG-2009-1304918) Paolo Gresele. The expert editorial assistance of Dr. S. Orsini is gratefully acknowledged. The authors report no conflict of interest.
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