State of the science conference: Initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: executive summary.

Patients with human immunodeficiency virus (HIV) infection have sustained alterations in metabolism (lipids and insulin/glucose homeostasis) and body composition (fat distribution) that are proatherogenic (the Figure). HIV infection itself and/or its therapies may contribute to these alterations (the Table); although most effects are reversible, there are some possibly irreversible consequences of treatment. With the relative restoration to health seen in the era of highly active antiretroviral therapy (HAART), many traditional risk factors and promoters of dyslipidemia and diabetes also are present; they interact with HIV-specific inducers to worsen dyslipidemia and to increase the prevalence of insulin resistance and diabetes. Figure. Overview of the effects of HIV and its therapies on CVD risk. The contribution of traditional risk factors must be kept in mind, and they may occur with increased prevalence in people with HIV infection (eg, smoking). HIV, likely through the inflammatory response, and antiretroviral therapies independently affect many of the mediators of CVD risk. The effects on lipids are a prominent but complex example; HIV infection lowers LDL levels, but antiretroviral therapy raises LDL back up to normal levels. The bidirectional arrows indicate associations, but there is not yet adequate proof of causality. The dotted arrow between body composition and CVD indicates that body fat is known to affect the mediators such as dyslipidemia and insulin resistance but may also have a direct effect. FFA indicates free fatty acids; ARV, antiretroviral. View this table: Table. Effects of HIV Treatment These disturbances in lipid and glucose metabolism and renal disease may contribute, at least in part, to the excess cardiovascular disease (CVD) morbidity and mortality observed in HIV-infected individuals (the Figure). However, the relative contribution to excess CVD risk of traditional CVD risk factors, especially smoking, compared with these infection- and treatment-specific complications requires clarification. More prospective data with multivariable modeling are needed. …

In the more than 30 years since AIDS was first recognized, there has been a sea change in the challenges facing human immunodeficiency virus (HIV)-infected patients and their caregivers.Now that antiretroviral therapy (ART) suppresses viral replication and prevents AIDS-related complications in the majority of HIVinfected patients [1], different clinical problems from those faced in the first decades of the epidemic have emerged.In particular, chronic conditions typical of aging, including cardiovascular disease, diabetes, bone fractures, and malignancies, are occurring in HIVinfected patients at a higher rate and at an earlier age than in uninfected individuals [2].To provide an overview of the current state of our knowledge and a guide to future approaches for meeting these challenges, the Harvard University Center for AIDS Research organized a multidisciplinary symposium on metabolic and cardiovascular complications in HIVinfected patients; this supplement is an outgrowth of presentations made at that symposium.Among the most important clinical problems facing HIV-infected patients is a rising rate of cardiovascular disease.The World Health Organization projects that ischemic heart disease will be the leading cause of death in the general population in both low-and high-income

In the mid-1990s, case reports of myocardial infarction (MI) in young patients infected with human immunodeficiency virus (HIV) sparked interest in the relationship between HIV infection and cardiovascular disease (CVD).1,2 Although the initial focus was primarily on the relationship between dyslipidemia associated with antiretroviral therapy (ART) and cardiovascular risk, a broader appreciation of the complex interplay between traditional risk factors for CVD and HIV infection has emerged more recently. Several groups of investigators have designed studies to examine various aspects of the relationship between HIV infection, traditional cardiovascular risk factors, ART, and short- and longer-term cardiovascular risk3–11 (see also Working Group 1). Studies have included both clinical end points (MI, hospitalization for MI or angina, and revascularization) and surrogate markers of atherosclerosis (endothelial function or carotid intima-media thickness). Successive studies have generally improved in quality, with inclusion of data on traditional risk factors, longer follow-up, and more diverse patient populations. HIV and ART can contribute to an altered risk of CVD in 3 principal ways: (1) HIV may serve as a marker to identify a subgroup of the general population with an altered prevalence of traditional cardiovascular risk factors, unrelated to HIV or ART (eg, HIV-infected patients may have higher smoking rates); (2) HIV or ART may affect the risk of developing a traditional cardiovascular risk factor (eg, HIV or ART may worsen dyslipidemia); and (3) HIV or ART may affect the pathogenetic process that leads to CVD in ways other than via an effect on traditional risk factors (eg, through effects on inflammation or endothelial function). Importantly, there is substantial evidence to suggest that all 3 mechanisms are in operation and affect the risk of CVD in patients infected with HIV. All 3 factors should be considered in epidemiological studies assessing the relationship between CVD and HIV …

Human immunodeficiency virus (HIV)–infected individuals are living longer in the era of antiretroviral therapy. As a result, they are increasingly prone to the development of concomitant chronic disease. Coronary heart disease (CHD) is the leading cause of death in the United States and Europe. Recent studies suggest that CHD rates may be increasing among HIV-infected patients (see Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy, Working Group 2), and thus appropriate screening strategies for CHD in this population are needed. Recently, approaches to screening and assessment of cardiovascular disease (CVD) in HIV-infected individuals were discussed at a State of the Science Conference. Although insufficient evidence now exists to recommend a screening strategy for CHD in HIV that differs from that recommended in the non-HIV population, emerging risk factors and surrogate markers for atherosclerosis unique to the HIV population suggest specific strategies that may be useful in this population. Two broad screening categories are discussed here. The first screening strategy seeks to define the pretest likelihood of disease by identifying the presence of predisposing risk factors such as hypertension, elevated serum cholesterol, cigarette smoking, and physical inactivity. The second screening strategy aims at the detection of established CHD, even in its earliest stages. The currently available recommendations and guidelines for screening for the presence of cardiovascular risk factors in the general, non–HIV-infected population are detailed in Table 1.1–7 View this table: Table 1. Recommendations and Guidelines for Screening for Cardiovascular Risk Factors in the General Population The currently available recommendations and guidelines for screening for the presence of CVD risk factors in persons with HIV infection are detailed in Table 2. These recommendations take into account the evidence for dyslipidemia, insulin resistance, and changes in body fat distribution that have been shown to occur …

Effective antiretroviral therapy (ART) improves the survival of patients with human immunodeficiency virus (HIV) infection.1 With increased life expectancy, HIV-infected patients increasingly are experiencing complications of illnesses that are not directly related to HIV infection.2 Cardiovascular disease (CVD), the leading cause of death in the United States,3 recently has been recognized as an important cause of morbidity and mortality among patients with HIV (see Working Group 2, Epidemiological Evidence for Cardiovascular Disease in HIV-Infected Patients and Relationship to Highly Active Antiretroviral Therapy).2,4–6 Among these patients, traditional CVD risk factors predict CVD events; however, certain components of ART appear to be associated with increased CVD risk.5 Much of the increased CVD risk observed in patients undergoing ART is related primarily to the effects of ART on traditional CVD risk factors; however, direct effects of ART on the vasculature and other inflammatory, immune, and viral factors associated with HIV infection may also contribute to increased CVD risk.5,7,8 A central tenet of preventing CVD is that the intensity of risk-reducing interventions should be based on the level of CVD risk.9 Patients with established CVD are at the highest risk and qualify for the most aggressive risk factor management, with special focus on interventions that have been proven to prevent cardiovascular death, myocardial infarction, and stroke. For patients without established CVD, management is based on the presence of risk factors for developing complications of CVD, such as death, myocardial infarction, and stroke9–12 (see Working Group 4, Screening and Assessment of Coronary Heart Disease in HIV-Infected Patients). The intensity of CVD risk-reducing therapy, however, must be modified by the context of the patient’s overall health. This is an especially important consideration in patients with HIV infection, who often have competing morbidities that may be as likely to …

S tudies published over the past 3 years have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac illness in both children and adults. 1 These studies show that subclinical echocardiographic abnormalities independently predict adverse outcomes and identify high-risk groups to target for early intervention and therapy.The Joint United Nations Program on HIV/AIDS estimates that 36.1 million people were living with HIV infection at the end of the year 2000. 2 If 8% to 10% of patients develop symptomatic heart failure over a 2-to 5-year period, 3 then 3 million cases of HIV-related heart failure will present during that period. 1 Cardiovascular manifestations of HIV have been altered by the introduction of highly active antiretroviral therapy (HAART) regimens.On one hand, HAART has significantly modified the course of HIV disease, lengthened survival, and improved the quality of life of HIV-infected patients.On the other hand, the early data have raised concerns that HAART is associated with an increase in both peripheral and coronary arterial diseases. 1The HAART-associated changes are relevant only to the minority of HIV-infected individuals worldwide who have access to HAART.Thus, studies conducted before HAART became available remain globally applicable.In this review article, the principal HIV-associated cardiovascular manifestations will be discussed, with an emphasis on new knowledge about prevalence, pathogenesis, and treatment.

With the development of effective therapies against human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection has become a major cause of morbidity and mortality among patients with both infections (coinfection). In addition to the high prevalence of chronic HCV, particularly among HIV-infected injection drug users, the rate of incident HIV infections is increasing among HIV-infected men who have sex with men, leading to recommendations for education and screening for HCV in this population. Liver disease is the second leading and, in some cases, a preventable cause of death among coinfected patients. Those at risk for liver disease progression are usually treated with a combination of interferon (IFN) and ribavirin (RBV), which is not highly effective; it has low rates of sustained virologic response (SVR), especially for coinfected patients with HCV genotype 1 and those of African descent. Direct-acting antivirals might overcome factors such as immunodeficiency that can reduce the efficacy of IFN. However, for now it remains challenging to treat coinfected patients due to interactions among drugs, additive drug toxicities, and the continued need for combination therapies that include pegylated IFN. Recently developed HCV protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and RBV, could increase the rate of SVR with manageable toxicity and drug interactions. We review the latest developments and obstacles to treating coinfected patients.

Achieving the targets set by UNAIDS for the year 2020 will enable the world to end the AIDS epidemic by 2030. Combination antiretroviral treatment (ART) is key to success of this goal and expanding access to all who need it, an imperative. Human immunodeficiency virus (HIV), ART, and traditional cardiovascular risk factors have all been implicated in the pathogenesis of cardiovascular disease in HIV-infected patients, either separately or collectively. The HIV replication in infected patients without ART is associated with an increase in cardiovascular disease risk, which seems to reduce with ART. Proinflammatory cytokines maintained with HIV infection and associated with endothelial activation leading to a proatherogenic profile appear to improve with ART. Associations between protease inhibitors and increased triglycerides, low-density lipoprotein, and total cholesterol have been demonstrated. Although ART use has been associated with an increased cardiovascular risk in HIV-1-infected patients, the overall mortality benefit of ART seems to outweigh the cardiovascular risk. In the context of ART, traditional risk factors have been shown to be strong predictors of cardiovascular disease. Emphasis should be placed on assessment for and management of traditional risk factors. ART with less cardiovascular toxicity should be selected. Early initiation of ART is now recommended.

Patients with human immunodeficiency virus (HIV) infection are at increased risk of developing coronary heart disease (CHD). Although factors potentially contributing to this elevated risk include traditional CHD risk factors and antiretroviral medications, more recent data support a role for inflammatory and immunologic factors as central to a complex mechanism. Decreasing CHD risk among HIV-infected patients is likely to involve modification of inflammatory and immunologic factors through antiretroviral therapy or other novel strategies as well as targeted treatment of traditional CHD risk factors. This review will highlight epidemiologic data investigating the association between HIV and CHD outcomes. An overview of potential mechanistic factors associated with CHD in HIV infection and of strategies for managing CHD risk in HIV-infected patients is also included. Specific cardiovascular and metabolic risk factors, CHD risk prediction, and the immunologic basis for CHD in HIV-infected patients will be discussed in separate reviews.

With the success of antiretroviral therapy (ART), a dramatic decrease in viral burden and opportunistic infections and an increase in life expectancy has been observed in human immunodeficiency virus (HIV) infected individuals. However, it is now clear that HIV- infected individuals have enhanced susceptibility to non-AIDS (Acquired immunodeficiency syndrome)-related complications such as cardiovascular disease (CVD). CVDs such as atherosclerosis have become a significant cause of morbidity and mortality in individuals with HIV infection. Though studies indicate that ART itself may increase the risk to develop CVD, recent studies suggest a more important role for HIV infection in contributing to CVD independently of the traditional risk factors. Endothelial dysfunction triggered by HIV infection has been identified as a critical link between infection, inflammation/immune activation, and atherosclerosis. Considering the inability of HIV to actively replicate in endothelial cells, endothelial dysfunction depends on both HIV-encoded proteins as well as inflammatory mediators released in the microenvironment by HIV-infected cells. Indeed, the HIV proteins, gp120 (envelope glycoprotein) and Tat (transactivator of transcription), are actively secreted into the endothelial cell micro-environment during HIV infection, while Nef can be actively transferred onto endothelial cells during HIV infection. These proteins can have significant direct effects on the endothelium. These include a range of responses that contribute to endothelial dysfunction, including enhanced adhesiveness, permeability, cell proliferation, apoptosis, oxidative stress as well as activation of cytokine secretion. This review summarizes the current understanding of the interactions of HIV, specifically its proteins with endothelial cells and its implications in cardiovascular disease. We analyze recent in vitro and in vivo studies examining endothelial dysfunction in response to HIV proteins. Furthermore, we discuss the multiple mechanisms by which these viral proteins damage the vascular endothelium in HIV patients. A better understanding of the molecular mechanisms of HIV protein associated endothelial dysfunction leading to cardiovascular disease is likely to be pivotal in devising new strategies to treat and prevent cardiovascular disease in HIV-infected patients.

HAART and the HCV-infected liver: friend or foe?

HIV Infection and Cardiovascular Disease

HIV disease: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

Effective highly active antiretroviral therapy (HAART) for human immunodeficiency virus-1 (HIV) infection has led to marked improvement in life-expectancy for those infected with HIV. Despite reductions in the incidence of AIDS with effective treatment, patients continue to experience considerable morbidity and mortality from non-AIDS illness such as premature cardiovascular disease, liver failure and renal failure. These morbidities, particularly premature cardiovascular disease, are thought to be related to a combination of the effects of an ageing HIV-infected population coupled with long-term effects of HIV infection and antiretroviral therapy (ART). One of the principle drivers behind the well documented increase in the risk of cardiovascular disease in HIV-infected patients is dyslipidemia.This review will focus on the clinical presentation of HIV and ART-associated dyslipidemia, what is known of its patho-physiology, including associations with use of specific antiretroviral medications, and suggest screening and management strategies.

With effective antiretroviral therapy, cardiovascular disease has gained importance as a cause of morbidity and mortality in HIV-infected persons. We review the risk of cardiovascular disease in HIV-infected persons compared with that in uninfected persons and discuss the relative contributions of host, HIV, and antiretroviral therapy in the light of current knowledge. The incidence of cardiovascular disease in HIV-infected patients receiving antiretroviral therapy is low. However, the risk of cardiovascular disease increased compared with that in uninfected persons. This fact is substantially due to a higher prevalence of underlying traditional cardiovascular risk factors that are mostly host dependent. HIV may additionally contribute both directly through immune activation and inflammation, and indirectly through immunodeficiency. In a more modest way than that of HIV infection, the type of antiretroviral therapy may also contribute through its impact on metabolic and body fat parameters, and possibly through other factors that are currently unclear. Prevention of cardiovascular disease in HIV-infected patients should be standard of care. Traditional risk factors should be investigated and aggressively treated when possible. Antiretroviral therapy should be initiated earlier in patients with high cardiovascular risk. From a purely cardiovascular perspective, the benefits of antiretroviral therapy clearly outweigh any potential risk.