FOCUS ISSUE ON HIV AND THE CARDIOMETABOLIC SYNDROME

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Infection with human immunodeficiency virus (HIV), use of highly active antiretroviral drug therapies (HAART), undesirable lifestyle/behavioral choices, genetic background, and other factors all contribute to adverse metabolic and morphometric changes in appreciable numbers of adults and children living with HIV. At least in the developed world, HIV/AIDS has transitioned from certain death to a chronic, manageable condition with the potential for long-term salubrious survival, due to therapeutic advances made over the past 10yrs. But many challenges remain, as outlined by the articles in this volume of the Journal of the CardioMetabolic Syndrome. With longer-term survival, will HIV-infected people succumb to the causes of death that are most common among aging humans in the industrialized world, especially components of the cardiometabolic syndrome (heart disease, stroke, lung disease, diabetes), but at an earlier age? Does HIV-infection and the accompanying chronic proinflammatory processes, impart increased risk for these most common causes of death? Are there HIV-specific risk factors for the cardiometabolic syndrome? Recent observational data indicate that deaths from cardiovascular disease, diabetes, non-HIV-related cancer, and drug abuse may be increasing among HIV-infected people (4-8). In addition, socioeconomic and demographic data from the CDC suggest that low-income, poorly educated, young minority men and women with poor access to health care constitute a disproportionate percentage of people newly infected with HIV (2, 3). Are these not the same groups in the general population that are at greater risk for developing diabetes, obesity, heart disease, and cancer? Likewise, the HIV epidemic is most serious in resource-limited areas of the world. As these regions become more developed and industrialized, we anticipate a "collision of epidemics"; HIV and the cardiometabolic syndrome, and recent analyses support this notion (1). The issues are complex and will require multidisciplinary teams and approaches to resolve. The more fundamental questions are left to be resolved by the biomedical scientists (i.e., the contributing authors to this volume and their peers) and include: Are we being alarmist? After all, we only have 10yrs of experience with antiretroviral medications. Maybe newer medications and treatment paradigms will have fewer toxicities. What are the underlying mechanisms that link HIV, HAART, lifestyle habits, and genetic predisposition to the development of cardiometabolic syndromes? Do these mechanisms point us to established or novel therapeutic interventions for the cardiometabolic syndrome in HIV? By studying cardiometabolic syndrome in HIV, can we learn more about the pathogenesis of cardiometabolic syndrome in the general population? Are there interactions between the immune and cardiovascular systems that we are overlooking? Can technological and analytical advances (e.g., imaging, "omics", RNA knockdown) help us identify, characterize, or treat the evolving cardiometabolic syndrome in HIV? How can we develop, test, and implement better screening, monitoring, and treatments for the cardiometabolic syndrome in HIV in all parts of the world? Does the research and knowledge gained about HIV and HAART in the developed countries, properly inform providers about how to treat and manage HIV-infected people in resource limited regions of the world? These are all difficult questions. They strongly suggest that research on HIV and the cardiometabolic syndrome must continue to receive support. We propose that research efforts have only scraped the "tip of the iceberg". Given our limited experience with HAART and the complexities of HIV-replication, combined with our extensive knowledge of the proatherogenic disposition of dyslipidemia, inflammation, visceral adiposity, insulin resistance, poor eating behaviors and physical inactivity, one can only envision that this is the "tip of the iceberg" for a future epidemic of cardiometabolic syndrome in people living with HIV. We hope that scientists and clinicians continue to seek unbiased knowledge and the truth about these issues, and that granting agencies and policymakers respond to this knowledge appropriately.