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Global Consequences of the Future of Aging with HIV
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from Jules Levin
We have not yet begun talking about the future consequences of a large significant patient population aging with HIV in the USA and the Western world, although we have just recently started discussing the science of aging. If aging with HIV develops into a serious problem which many think it is likely to, we will be faced with an aging population of men and women, but early epidemiology shows men may be more affected, who will be more frail, have more disease conditions, who may die earlier, are at risk for early bone fractures which among HIV-negatives is associated with mortality, and of particular note will require more intensive services of various kinds. This threatens to affect our entire care system, which of course is related to potentially a strained funding and services infrastructure, and these questions deserve attention and discussion. How will we address these questions and will we discuss these questions?? Below is a discussion of the health conditions that may in an accelerated way be affecting HIV+ individuals. Over the past year there has in fact been an increase in attention being paid to the science of aging with HIV, although we are only in the very early stages of addressing these issues, and we have a long way to go just to to understand the situation. But we have yet to begin to discuss the effect on our care infrastructure, not only in the Western developed world BUT also in the developing world. The effects of aging will also affect those in the developing world, in Africa, Asia, and all over. The affects may however be much worse in the developing world. So we owe it to everyone to pay more attention to this question. Aging with HIV will become a global societal health problem.
We know from studies:
Perhaps the most important question, because it has yet received little attention, although attention has increased in the last year is inflammation; as well as premature senesence or aging in HIV. Several studies report premature decline in immune function, what staves off early disease and experienced by the elderly, and called senesence, occurs soon after HIV-infection, and has been characterized by changes in the T-cell repertoire. Inflammation has certainly received more attention and may be a cause of accelerated aging and disease among HIV+ individuals or may in part be a result of disease onset. Nonetheless researchers are beginning to pay greater attention to inflammatio, as studies have recently reported inflammation was associated with increased disease, morbidity, and increased moratlity, death. HAART treatment interruption was found to be associated with increased inflammation and with increased morbidity and mortality in the major studies recently reported in the last few years. Senesence has received very little attention, but it has received some attention and may receive hopefully more research attention and discussion, because it might play an important contributory role in the recently reported increased rates of nonAIDS morbidities and premature increased death rates in several big studies including EuroSida and DAD.
Research has reported HIV can be reservoired in the parts of the body affecting these diseases, or that HIV can affect the metabolic process of these diseases developing, and ART may play a role in certain circumstances.
Bone disease is a serious concern, with cohort studies in the USA reporting 50-60% osteopenia and 10-20% osteoporosis at an average age in their mid 40s. And one or two studies reporting increased fracture rates in HIV+ individuals compared to HIV-negatives. Among HIV-negatives these rates of bone disease affect only the elderly and result in increased risk for martality after a bone fracture occurs, so in bone disease prevention is the major hope. Yet, screening HIV+ patients for osteopenia with a bone dexa has yet to get traction or discussion, and education of doctors, providers, and patients has also yet to gain traction.
At CROI numerous studies reported increased neurological decline: cognitive impairment, increased neuropathy, and brain dysfunction, and a different type of cognitive impairment may be emerging, has been reported. And it's been said by HIV brain researchers that HIV+ individuals might be at increased risk for alzheimer's and similar diseases. Early therapy with certain nukes and perhaps HIV caused mitochondrial decline, but we have not adequately researched the effects on diseases and aging, as it might contribute to various disease states including bone disease and the CNS.
Among HIV-negatives kidney function declines as people so studies suggest that HIV+ individuals may be at an increased risk for kidney function decline as they age. Proteinuria is an important aspect of kidney function, as well as diabetes, insulin resistance, and cardiovascular disease. These diseases are al tied in with each other. Hypertension is a serious disease and is also tied into kidney function and heart disease.
Heart disease has already received quite a ot of attention, and tis remains a concern as both HIV and certain ARTs are associated with CVD decline. Of note HIV has been found by a number of studies to be associated with endothelial dysfunction and inflammation and of course ongoing immune activation regardless if viral load is undetectable and immune activation IS associated with chronic viral diseases in general.
The MACS group has published increased risk of up to 15 times for frailty among HIV+ individuals in mACS compared to HIV-negatives. And a 55 yr old in MACS was at increased risk for frailty compared to a 65 yr old HIV-negative person.
Diabetes is also a disease associated with aging. Whether or not overall rates in HIV will increase certainly many HIV+ individuals are at increased risk as they age for numerous reasons including perhaps due to certain ARTs and perhaps HIV and certainly lifestyle.
Cancers are a great concern as HIV+ individuals age, as increased incidence of many different types of cancers has been reported including anal cancer in men and women. Studies have reported CD4, immune deficits, and viral load associated with increased cancer risk. Several studies outside of HIV reported increased insulin associated with breast cancer and perhaps other cancers. The notion of insulin resistance among HIV+ individuals has yet to be addressed much at all, as it is a condition very much below the surface, if you will. Certainly the risk for increased cancer rates is a real concern as people age with HIV. Skin cancer has inextricably appeared as an increased risk among HIV+ in a few published studies and of course smoking cigarettes is associated with increased cancer risks.
Liver disease doesn't get much discussion any more, it remains the poor cousin, if you wil, perhaps due to the patient population it mostly affects: IDUs, blacks, latinos. But, an important aspect of liver disease is fatty liver which has been reported in several studies and conference reports to affect HIV+ individuals who do NOT have HCV or HBV. Fatty liver is associated with increased ALT and may be associated with increased risk as patients age for liver cancer and hepatitis. Certain nukes and side effects of ART and HIV may be associated with causing fatty liver. Increased lipids, lipid abnormalities, belly fat, perhaps lipoatrophy, metabolic abnormalities and increased glucose abormalities are all associated with increased risk for fatty liver. This is aside from the increased risk for liver disease facing the estimated 300,000 HIV+ individuals with HCV and HBV coinfection. For years liver disease, mostly HCV, has been the leading cause of hospitalization and death in HIV, and it remains the leading cause of death in HIV in the USA and Western Europe outside of course of AIDS. Unfortunately HCV has NOT gotten adequate funding attention and the treatment for HCV has been problematic, and many HCV+ individuals have already died. The near future promises much better therapy which will I am certain be accompanied by increased Federal and Stare and City funding support for screening and support services. In 2011 the first 2 oral HCV proteases inhibitors are expected to become available in the pharmacy. SVR rates, 'cure' rates, will increase immediately in treatment-naive patients significantly, as phase 2 studies so far report about 70% SVR rates in treatment-naives. But these studies were not conducted in the worst-case scenario patient populations. SVR rates will be higher but will still be a concern in HIV coinfected people of color, as peginterferon and ribavirin will remain at least for now part of the therapy. The real breakthrough for this hard-to-treat patient population will come when 2 and then 3 new oral HCV antivira medications become part of the therapy regmen, and this is only everal years away. With a regimen consisting of 2 orals, protease inhibitor + a polymerase inhibitor plus pegIFN/RBV SVR or cure rates will increase I expect to perhaps 85% or more in treatment-naives and with 3 orals plus peg/RBV SVR rates I expect will be higher. The prospect of a regimen of 3 or more oral therapies without peg/RBV will be the object of research very soon to see IF they can eliminate peg/RBV from treatment but this remains an open question until proven. Still, with 3 orals plus peg/RBV SVR rates approaching 100% in easy to treat treatment-naive patient populations can realistically be expected. In hard-to-treat patients, the hardest to treat are HIV+ African Americans, Latinos, and others who are peginterferon resistant I expect SVR rates to still be very high with 3 orals because these are antiviral drugs and NOT subject to reduced responses seen with peg and RBV by patients resistant to peg and RBV like HIV+ individuals, African-Americans, and Latinos. HBV, although treatment is on average effective, as Truvada is an effective treatment in controlling HBV, can become much more concering. HBV viral load, HBV DNA, is associated with increased risk for liver cancer so this can emerge as a problem in the future. As well, although HCV is curable with time-limited duration of therapy, HBV therapy can be for a lifetime, which opens up many potential future concerns regarding liver disease for HBV/HIV coinfected patients.
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