There is likely much that can be done to slow the process of functional decline, loss of quality of life, and early mortality that is currently ongoing among HIV-positive persons currently utilizing treatment. We can begin by learning as much as possible from the study of aging (gerontology) and the medical specialty of geriatrics; then we must tailor their lessons to the special issues affecting people aging with HIV.
First, geriatricians will tell us that the term "premature" aging is a bit of a misnomer; it suggests that aging is inevitably associated with decline and that early decline is unique to those aging with HIV. Organ system injury and failure, functional decline, repeated hospitalizations and death are also observed at earlier ages among those with other chronic diseases such as diabetes and rheumatoid arthritis.41 As with these other conditions, steps can be taken to regain or, preferably, maintain function and quality of life and thereby avoid a prolonged period of compromise prior to death.
Additionally, geriatricians will tell us that morbidity and mortality among those aging with HIV likely reflect the integrated whole of many conditions and disease processes -- some tied to the "primary disease" and its treatment, and some associated with health behaviors and conditions more common among those with the primary condition but not necessarily causally associated (e.g., hepatitis C infection).42,43 Interventions that systematically identify and address multiple contributing factors are more likely to succeed. These will include early treatment as well as behavioral interventions to improve adherence; end cigarette and tobacco use, alcohol consumption and drug use; and avoid obesity and support regular exercise. Diagnosis and treatment of comorbid illnesses, in particular hepatitis B and C, and careful consideration of potential treatment toxicity from HIV and non-HIV medications are also important.
Besides describing techniques to address the diverse etiologies that drive functional decline among those aging with complex chronic disease,44,45 the geriatric literature offers a general lesson for management. Geriatricians warn against the blind application of screening and treatment guidelines developed for application in a primary care population free of major comorbidity to those with complex chronic disease and multi-morbidity.46,47 Multi-morbidity is the norm among those aging with HIV.48 We must prioritize and tailor care for those aging with HIV based upon a careful assessment of their risk of morbidity or mortality, identification of risks which are modifiable, and targeted intervention based upon assessment and patient preferences.
The list of potentially helpful interventions is long and demanding for both providers and patients. Therefore, prioritization and tailoring of health care goals based upon a careful assessment of the individual risk of morbidity and mortality is essential.49,50 This assessment needs to go beyond CD4 count and viral load quantification. While a focus on CD4 count, viral load, and AIDS defining illnesses made sense when we had few effective antiretroviral therapies and mortality rates were high, it is no longer appropriate. As the SMART investigators have concluded, we now need to use a more nuanced approach which adapts research priorities to understand the role of HIV in a range of clinical diseases and enables clinicians to prevent and monitor for non-AIDS outcomes.
The geriatric research community is sharply divided regarding the best means of measuring the overall health or vulnerability to injury of an individual.51 A modified version of the frailty phenotype, the frailty related phenotype, has been applied among those with HIV infection with mixed success.52,53 Functional capacity, or the reported or observed ability of the individual to do certain physical activities, might be a more useful measure because functional capacity can be measured over a wider range of abilities, from activities of daily living like using the bathroom to extreme exertion like running uphill,54 and has demonstrated a wider applicability to HIV-positive individuals in care.55,56
The recently published Veterans Aging Cohort Study Risk Index (VACS Risk Index) offers a more comprehensive approach and direct insight into the likely contributing sources of injury. The VACS Index incorporates age, CD4 count, viral load, AIDS defining illnesses, hemoglobin, renal function, liver function, chronic hepatitis B and C, and diagnoses of alcohol and drug abuse and dependence.57 It predicts short and long term survival among those starting treatment better than an index restricted to CD4 count, viral load, and AIDS defining illnesses.58 The index has been developed and validated among veterans in care and the process is underway to validate it outside the Department of Veterans Affairs healthcare system. With further validation, indices such as the VACS Risk Index may prove a valuable tool to: 1) comprehensively assess risk of morbidity and mortality, 2) identify modifiable mediators of risk and 3) demonstrate the efficacy of early intervention.
However, additional work also needs to be done regarding how best to communicate the meaning of the index score both to people with HIV infection and to their health care providers. The VACS Project Team is developing a public website where individuals, or their health care providers, can enter clinical information and get the score and an interpretation. We would like feedback from people living with HIV and their providers on how to make this site more useful; the link can be accessed at www.vacohort.org.
Eventually, the use of a more comprehensive risk index can encourage patients and health care providers to think more broadly about the conditions contributing to the total burden of disease among those aging with HIV. This will help us recognize the inevitable tradeoffs between screening for and treating every possible comorbid condition and concerns about overly complex medical treatment which leads to increased rates of toxicity, drug interactions, and medical error. We must keep in mind that some conditions will have major impact on an individual's quality and quantity of life and others will not. Further, an overall index would allow us to uniformly measure benefit from health behavior changes including weight control, exercise, moderation or cessation of tobacco or alcohol, and discontinuation of drug abuse.
HIV and its consequences continue to play a central role in health outcomes. Additionally, those aging with HIV have different risks of other aging related conditions due to behaviors and conditions present previous to HIV. If we are to further extend the quality and quantity of life for those living with HIV and accessing treatment we must systematically recognize and measure overall organ system injury and its implication for the HIV-positive individual's risk of morbidity and mortality. Armed with this tool and a willingness to think more comprehensively about the cumulative effects of health behaviors, aging related comorbidity, and medication toxicity, we can continue to improve life for those aging with HIV.
It is likely too early to determine who should provide primary care to individuals aging with HIV. But it is clear that a greater dialogue is needed between those with expertise in antiretroviral therapy and geriatricians and generalists with expertise in the optimization of complex chronic disease management. Primary care guidelines will require adaptation and individualized tailoring if they are to have their intended effect of preventing disease and extending survival among those aging with HIV. Individual health behavior changes will likely be as important as new medications in improving overall health.
Amy C. Justice, M.D., Ph.D., is an associate professor at Yale University Schools of Medicine and Public Health and Section Chief of General Internal Medicine at West Haven VA Medical Center.
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