Foreword to the Second Edition

Highly active antiretroviral therapy (HAART) has changed the face of HIV infection and AIDS into a treatable, chronic illness in resource-rich areas of the world. The hope is that we will overcome availability and distribution issues in resource-poor settings so the same is true in these regions of the world in the future.

Cardiovascular diseases are especially important in this regard because of their prevalence in the population and their frequent relationship to morbidity and mortality. Whether the heart and vascular system are affected by HIV infection is in little doubt, although the extent of these effects in different populations, and the relative contribution of HIV infection compared to classical risk factors, is a matter of some contro­versy. Much data has accumulated to suggest that there are sig­nificant effects of HIV, and concomitant therapy, on the cardio­vascular system.

The chapters in this book describe what is clearly under­stood, and what is not. They go on to present the data upon which these opinions are based, and to make practical sugges­tions for proper diagnosis and management. They make impor­tant reading for researchers and clinicians in this field, both to provide the clinical basis for basic research that will inform new diagnostic and treatment paradigms, and to suggest the best, current therapies for these maladies.

Perhaps the most urgent area for research, leading to a more concise, mechanism-based understanding of pathogenesis, is HIV-associated lipodystrophy.This catch-all phrase actually sub­sumes several areas that may have distinct pathophysiologic eti­ologies. Lipoatrophy has in some ways become the new “scarlet letter” of HIV infection, a distinction previously held by cutaneous Kaposi’s sarcoma.The cause of this manifestation, characterized by thinning of the face, arms, legs, and buttocks, remains unclear, as does the relative contribution of HAART and HIV infection to these changes. Fat redistribution syndrome, characterized by fatty deposits of the neck and abdomen (“buffalo hump” and “pro­tease paunch”) most often occurs during HAART, but whether fat redistribution is associated with an increased risk of cardio­vascular disease, and whether lipoatrophy engenders similar risk, remains uncertain.

HAART may lead to changes in serum lipids, and it is likely that these changes increase the risk of atherosclerotic heart disease, myocardial infarction, and stroke. Whether or not these lipid changes during HIV infection carry the same, or greater, risk compared to the general population without HIV infection, it is clear that clinicians should measure these changes and treat them accordingly. In this context, it is often necessary to know the relative magnitude of lipid changes with various anti­retroviral agents so that treatment regimens can be modified appropriately if standard lipid-lowering therapy does not suf­fice. It is also crucial for clinicians to know the many drug-drug interactions that can occur and that modify the efficacy and tol­erability of antiretroviral drugs and lipid-lowering agents. Newer diagnostic modalities, that have both clinical and research applications, are currently being assessed, as are the best drugs to use in these situations.

Other metabolic changes that occur during HIV infection, or are modified by HIV infection, also affect cardiovascular risk and optimal treatment of these disorders.

Other HIV-related effects may occur directly on the myocardium or pulmonary tissues, and lead to cardiomyopathy or HIV-associated pulmonary arterial hypertension. As longevi­ty increases for those with HIV infection, a fuller understand­ing of these disorders becomes important for proper diagnosis and treatment. It is likely that the immune activation that occurs during HIV infection, even with effective HAART, is related to the expression of these diseases during HIV infec­tion. Once again, it is difficult to determine the relative contri­bution of HIV infection and risk factors such as amphetamine, tobacco, or cocaine use, but it is clear that HIV infection alone can lead to cardiomyopathy and HIV-associated pulmonary hypertension. There is an important need to understand the natural history of these disorders to better plan when certain diagnostic and therapeutic interventions should be initiated.

This book should be read by all those interested in the car­diovascular complications that occur during HIV infection. The gold mine of information contained herein will stimulate new ideas about pathogenesis, inform in vitro and animal model research to test these hypotheses, and lead to patient-oriented research and clinical trials to test practical interventions that might improve diagnosis and treatment of cardiovascular co­morbidities. In this context, the combined knowledge and expertise of scientists and clinicians in the fields of infectious diseases, lipid metabolism, endocrinology, cardiology, and other relevant subspecialties must be brought to bear to unravel the mysteries that still exist, so that we may optimally prevent ill­ness and care for those who suffer from the sometimes devas­tating effects of cardiovascular disease.

Paul R. Skolnik, MD Professor of Medicine Boston University School of Medicine Boston, Massachusetts, USA