HIV/AIDS and Aging:The Second Wave of the HIV/AIDS EpidemicMedical Considerations

By Tom Smith, Ph.D.

 

INTRODUCTION

There are a number of medical issues that emerge when a person with HIV/AIDS begins to age; a process that is considered to have begun around age 50. At the beginning of this article, let it be said before we begin that there continues to be a dearth of research on the subject. Moreover, mechanisms involving co-morbid conditions or those medical issues that arise concurrently with HIV/AIDS or are exacerbated by the disease that we are going to describe insofar as they relate to HIV/AIDS and aging are not clearly understood.

In early 2013 The Washington Blade newspaper reported that there will be three phases to a second wave of the HIV/AIDS epidemic: First, there will be an increase in positive test results that will present as full blown AIDS. This group is likely to be over 50 years of age. The second phase will emerge in those aging with HIV/AIDS over many years where they have developed drug resistance to their life saving medications and the third phase will be that the drug companies may cease research and production of other classes of drugs that can treat HIV/AIDS. It is likely that the first two phases are already occurring.

AGING BODIES, HIV TREATMENT and CO-MORBID CONDITIONS

Aging bodies come with their own problems that are common to all of us. Insofar as the relationship between aging with HIV/AIDS and the Highly Active Antiretroviral Therapies (HAART) which includes at least three different kinds of HIV/AIDS fighting drugs is complicated, we do know some facts. The greater the count of CD4 T-cells when HAART is initiated the longer a person will live and life expectancies can be predicted with some accuracy. At the “Red Ribbon, Silver Trends: Healthy Aging in the Era of HIV/AIDS” conference in New York late 2009 it was cited that a 20 year old with less than 100 T-cells, 100-199 T-cells and over 200 T-cells when beginning treatment can be expected to live to ages 52, 62 and 70 respectively. At age 35 under the same circumstances a person can be expected to live to 62, 65 and 72 years of age. This, unfortunately is only ⅔ that of the general population. As mentioned above, little is known about those over 65 with HIV and even less about the consequences of taking antiretroviral medications for decades.

It is felt that HAART can reduce but not eliminate the negative impacts of aging on the progression of HIV/AIDS . Nevertheless, since the 1980s it has been known that those who become positive as older adults do not do as well as those who began treatment in their youth or middle age. They die sooner from the disease itself or opportunistic infections (co-morbid conditions). It seems that in older HIV positive adults their immune systems respond slower to treatment. This may be a consequence of the natural shrinkage of the thymus gland where T-cells mature. The reduction of cytokines (cell signaling protein molecules) that regulate T-cell production and health also contribute to this situation. Older adults are then faced with an increased possibility of contracting pneumonia or not having a strong response to the vaccine. Additionally this situation can lead to chronic immune activation or inflammation, an issue discussed later in this paper.

Unfortunately, research is lacking because due to the paradoxical situation of having HIV and being old and experiencing co-morbid conditions rules out older adults from being considered in clinical trials. Thus, we do not know whether co-morbidities are associated with the virus, aging, HAART or some other factor or combinations of the above. In any case, HIV positive people are likely to have more diseases than HIV negative people.

To be clear, low CD4 counts have been associated with increased morbidity and mortality. These low counts, for example < 200 have been linked to an increased risk of heart disease, kidney disease, liver disease and cancer. This is especially true when the reduction of T-cells occur in the gut where HIV replicates most intensely. So, HIV and aging has a dramatic effect on a person’s immune system and probably accelerates the aging process. Most HIV positive people have T-cell counts that are those of individual 20 – 30 years older. Immune systems of older adults do not recover as rapidly as those who are younger. This does not bode well with those diagnosed with HIV/AIDS later in life and these are the people who are becoming evermore infected! Many assume that they are older and so cannot have the disease or hide their sexual behavior from themselves or their physician or other health care provider. Then, when the disease does present itself and the diagnosis is made, things are so far along the person has full blown AIDS and the prognosis is very poor.

TWO POPULATIONS and the DANGEROUS SIDE EFFECTS OF MEDICATIONS

It helps to keep in mind that there are two distinct populations with some common, but also very different concerns. Those who are infected later in life and diagnosed long after they have been infected and those who have been diagnosed in their youth or middle age and on HAART for many, many years. Those diagnosed later in life; i.e., over age 50 are susceptible to increased mortality and early onset of serious co-morbid conditions than those with HIV for many years who have not progressed to the complications. However, those who have benefited from HAART may be faced with side effects and interactions and other problems.

LIVER, KIDNEY and CARDIOVASCULAR DISEASE

Some studies indicate those who have been treated for decades are at increased risk for heart attack especially if they have been taking protease inhibitors (a class of the HAART drug regimen). One drug, a nucleoside analogue called abacavir, seems to increase the risk of heart disease due to probable increasing inflammation. Another drug called Epzicom, which is a combination of abacavir and lamivudine, comes with a warning card that states the patients taking Epzicom may have a serious allergic reaction that within hours can cause death, citing a group of 5 different symptoms of concern. In short, we do not know what the consequences are of taking these very powerful drugs for many years. Moreover, antiretrovirals are not without their side effects which include lipodystrophy, facial wasting, wasting in general, pancreatitis, osteoporosis, liver toxicity, kidney problems, peripheral neuropathy and the build up of lactic acid. The increase of effective therapies for HIV have also increased side effects, most recently included are obesity, insulin resistance, high blood pressure and increased levels of fat in the blood thus, increasing the opportunity for heart disease.

Liver and kidney disease are of grave concern. Diseases of the liver caused by hepatitis infection, alcohol use, and diabetes is the most common non-AIDS related complication as a cause of death in HIV positive people and older people as defined above have four times the risk of liver related mortality than younger people. Low CD4 counts are found to increase this risk. Also contributing to this risk is liver toxicity due to medications and liver disease can lead to diabetes which is higher in HIV veterans in this time of cocktail therapy than before HAART was introduced. Those who are or were IV drug users are likely to have the hepatitis C virus and thus, face an elevated risk for liver disease. Declining kidney function is associated with HIV and aging. As the older HIV positive population increase so follows kidney disease especially among Africa-Americans.

Of concern as mentioned above is the interactions of HAART with drugs taken to treat co-morbid conditions. For example, those with HIV and hepatitis on HAART and taking cholesterol medications have been shown to have a much greater susceptibility to liver toxicity and an increased risk of death from liver disease. Reprising the above, the risk of heart disease cannot be discounted; it is strongly associated with age in those infected with HIV; albeit, it is a significant problem in the general population and is the leading cause of death in the United States. One study found a 26% increase in the rate of myocardial infarction per year of taking HAART during the first 4 – 6 years of treatment. Low CD4 counts have been persistently linked to a higher risk of heart disease.

CANCER

People with HIV have a generally increased risk of cancers of various types; this is exacerbated by old age. These non-AIDS related cancers (NARCs) include a higher incidence of melanoma, leukemia, non-Hodgkin’s lymphoma, colorectal, renal (kidney), anal, vaginal, cervical, liver, lung, mouth and throat and digestive tract cancers. In the case of anal cancer, it is found to be 40 times more likely in men who have sex with men (MSM) who are HIV positive. The most common of these cancers are those involving the lungs, digestive tract, blood and anal canal. Factors that contribute to the development of these problems include smoking, drinking excessively, increased age and chronic hepatitis B infection. However, the relationship of these cancers to HIV is not clearly understood and researchers reach contending conclusions. In the 1980s, one of the defining symptoms of AIDS was Kaposi’s Sarcoma, a cancer of dark purple lesions covering the body.

So, one has cause to be concerned with increased risk of heart disease, liver disease and non AIDS related cancers.

CHRONIC INFLAMMATION

Chronic inflammation, the body’s complex response to harmful stimulate such as pathogens and cell damage, is increasingly discussed when addressing aging and HIV/AIDS. The early onset of age related diseases and immune system deficits appears to be likely due to chronic inflammation. In many ways AIDS is an inflammatory disorder. “Accelerated aging” seems to be related to chronic inflammation, chronic immune activation and immunosenesence (aging of the immune system) in HIV infection; this is revealed throughout the presence of particular medical markers as certain reactive proteins. Metabolic abnormalities are also associated with inflammation. In both aging and HIV infection the deterioration of the immune system is marked by an increased proportion of CD28-, CD57+ memory CD8+ T cells with reduced capacity to produce interleukin 2, increased production of interleukin 6, resistance to apoptosis (the body’s programmed cell death) and shortened telomeres (a complex structure at the end of a chromosome). Many studies show increased levels of the biomarkers of inflammation in HIV infection and an association of these levels with poorer prognosis and increased mortality. However, it is still unclear how to treat those patients that present with these inflammatory biological markers or whether treating inflammation will reduce risk of disease. Nevertheless, it remains a critical variable in research studies.

Inflammation may also increase the frailty of HIV people who are aging. Frailty can be defined as weight loss, exhaustion, inactivity and slowness. HIV positive people are 5 -10 times more likely to present symptoms of frailty than those who are not infected. This is exacerbated by age, term length of infection, low CD4 counts and high viral load. Bone loss, ordinarily a concern of anybody who is getting old is of even greater concern to those with HIV. Osteopenia presents early and must be followed closely so not to lead to osteoporosis. Initiation of HAART treatment seems to be associated with bone loss and that certain combinations of medications lead to this condition. Smoking is also a factor.

Chronic inflammation, active substance abuse, including tobacco, marijuana and alcohol as well as the presence of other serious infections such as hepatitis C have been documented to contribute to neurological deficits including cognitive decline and dementia. As recently as 2010 it is found that HIV infected patients lose brain functional abilities 15 -20 years earlier than others either because of HIV itself or the treatments used to control it. We are speaking about a decline in attention, speed, flexibility, memory and problem solving. HIV and aging have profound effects on the brain and appear to be predictors of neuropsychological impairment. Before the introduction of HAART treatment HIV related dementia was found to be three times more frequent among HIV positive people older than 75 than those under 35 years. More recently it was found that those subjects 50 – 67 years of age with detectable virus in their spinal fluid were twice as likely to have psychological impairment than those with no detectable virus.

THE BRAIN

Also, blood flow to the brain is reduced to levels found in much older people in HIV positive individuals. Older people with HIV/AIDS are complaining to their care providers that they are experiencing memory loss, confusion and other cognitive functions. It seems that when HIV crosses into the brain that they support cells that release immune factors that harm neurons. Reduction in blood flow in the brain is a significant factor in these neurological problems. It is still unclear whether the virus, medications or both are affecting the brain. Beau Ances, M.D. and Steven G. Deeks, M.D. both concur that the origin of neurocognitive impairment of aging in HIV infected people to be complex and controversial, but nevertheless, appears to be associated with accelerated aging of the brain.

DEPRESSION

Depression remains an intransigent problem with those with HIV. Depression, a psychiatric; therefore, medical disorder is the most common co-morbid condition presented in those older people living with HIV/AIDS and ⅔ of these people were diagnosed as “moderately depressed”. Almost anyone would be depressed after getting an HIV/AIDS diagnoses, but it is even more devastating when you are older and perhaps, least expect such a thing. In 2010 in an article in “AIDS Care”, data from the Research on Older Adults with HIV (ROAH) study were further analyzed and showed that almost 40% of the participant’s developed symptoms of major depression and much of this was most importantly related to increased HIV associated stigma, increased isolation and loneliness, decreased cognitive functioning and reduced levels of energy.

It appears to be a collection of factors that lead to such an acute and intractable depression. As was mentioned in another part of this course, older people with HIV, especially the newly diagnosed, fear isolation and stigma even more than dying. Think for a moment about the scenarios: Perhaps one has been sexually active, male or female, in their 50s or 60s, heterosexual and found that they are HIV positive or the severe illness they have is really full blown AIDS. One is seized with fear and the imagination runs wild. Fear of rejection, stigma and stereotyping by family, friends or the healthcare system; especially, outside of major metropolitan centers where something like this is totally unexpected and not planned for interns of strategic public health care treatment plans, dominates the individuals world view.

Of course, this situation and others similar to it, for example, if the person happens to be a person who has sex with men and is not out or does not identify himself as homosexual finds that he is HIV positive or has full blown AIDS, not only leads to severely aggravating the illness and making things worse, but also can lead to suicidal outcomes. Already suicide among the elderly is higher than in the general population; so, such an outcome is not outside the realm of common possibility, thus, suicidality must be assessed early on in the diagnosis of HIV/AIDS in those over 50 years of age. Those who have been living with the disease for years or decades face two possible outcomes: They have come to grips with their situation and have treated and managed their depression and found new social outlets (friends) or support systems or they have grown tired with their situation, perhaps exhausted their financial resources and have outlived their friends or have no social support, grow weary or feel desperate and also think of taking their lives.

It is important to remember that when the epidemic broke out over 30 years ago and there were no treatments for it and the sure outcome was death, many people chose to take their own lives. Sometimes this is not an unreasonable choice and not an act of foolish impulse. Such thinking must be discussed with older adults living with or newly diagnosed with HIV/AIDS. Also, it must be kept in mind that over half of those living with HIV/AIDS are homosexual men, most of them now older; not to say that younger men are not being infected. In this population, one is dealing with a triple stigma of not only having HIV/AIDS, but also of being old and homosexual. One’s sense of self worth can take a beating. This issue is even more intense in the transgender community who face four or more stigmatic factors. Poor outcomes are greater in this population than any other.

Rates of infection continue to rise in the homosexual male population in their 20s. If successfully treated, they become the next “second epidemic” of older people living with HIV/AIDS.

SUBSTANCE ABUSE

One reaction to depression is often “self-medication” or in other words, substance abuse. Moreover, many people with HIV/AIDS have used tobacco, cannabis, alcohol or other illicit drug such as cocaine, heroin or crystal meth during their lifetimes. Old habits die hard and assessment must be done for substance abuse. Older people use drugs and often keep it secret. Increasingly, it is prescription drugs that are abused. Older people also use methedrine and engage in risky sexual behaviors such as unprotected anal sex or multiple sex partners or use injection drugs which put them at risk of contracting HIV. HIV transmission through injection drugs accounts for more than 16% of AIDS cases among those 50 or older. Older people who use injection drugs tend to be poorer and have far less social support than others. Of course, substance abuse can contribute to a variety of cognitive decline.

DAILY FUNCTIONING

“Activities of Daily Living” tend to decline in older people. In older people with HIV/AIDS this is even more so due to the debilitating nature of the disease and medical factors noted above, but also due to isolation, fear and stigma. In November 2012, the Department of Psychiatry at the University of California, San Diego conducted a study to determine whether HIV infection and aging act synergistically to disrupt everyday functioning. One hundred three HIV positive and 87 HIV negative participants were administered several measures of everyday functioning, including self report indices and instrumental and basic activities of daily living (ADLs) as well as other objective measures of functioning including the Karnofsky Performance Status Scale that goes from 100, indicating normal, no complaints to 60, indicating requires occasional assistance but is able to care for most of his personal needs to 50, indicating requires considerable assistance and frequent medical care to 10, indicating a moribund state where fatal processes are progressing rapidly. It is much like the Global Assessment of Functioning (GAF) more commonly used.

The results indicated a statistically significant interaction of effects of HIV and aging on declines in instrumental and basic activities of daily living. Significant interactive effects were also observed on emotional functioning sub scales . General health perceptions were poorer in the HIV positive group. Significant predictors of poorer functioning include major depressive disorder for all outcomes, co-morbid medical conditions, lower estimated pre-morbid functioning, neurocognitive impairment and very low CD4 counts.

The conclusion reached suggest that older age may exacerbate the adverse effects of HIV on daily functioning which emphasizes the importance of evaluation and monitoring of the functional states of older HIV positive adults. Early detection of functional deficits could obviously facilitate the delivery of compensatory strategies and assistive services.

LIVING WELL WITH HIV: Dental Health, Good Nutrition and Exercise.

An entire paper can be devoted to this subject, but we will address briefly some major concerns for older adults. Firstly, it is important to have one’s blood (especially CD4 T-cell counts and metabolic panels), viral load (the amount of virus in the blood) and general health evaluated once every three months at a minimum.

Not to be overlooked or dismissed is the importance of proper dental hygiene monitoring and care. Often as people age they begin to forget the importance of taking care of their teeth, mouth and gums. After years of neglect they can have many problems, especially if they have been abusing drugs like meth or smoking or drinking excessively. This is especially dangerous in older people with HIV. Poor dental hygiene opens the door to opportunistic infections, cancers and heart disease. Often the first signs of full blown AIDS can appear in the mouth; for example, candidiasis or thrush, a fungal infection in the mouth appearing as white fuzzy patches on the tongue or throat or the insides of the cheeks. One must also be aware of leukoplakia, or white patches that cannot be scraped off easily like thrush. They may indicate incipient oral cancers. Older people with HIV/AIDS should be urged and counseled to consult a dentist or oral hygienist if they have not had an oral examination in many years.

Good dental health absolutely helps with maintaining good nutrition. You need teeth to eat properly and a healthy mouth makes food taste better. Many HIV positive older adults can benefit from nutritional interventions. The risk of developing metabolic problems occurs naturally as people age regardless of HIV status; however for HIV positive older adults it is even more so. Many of the medications to treat HIV can cause metabolic imbalances including high cholesterol, triglycerides and blood sugar. There can be unwanted weight loss or gain as well as loss of bone density and muscle mass. These conditions can lead to multiple severe complications including cardiovascular disease, osteoporosis, diabetes and immune suppression. Evaluation and modification of diet and behavioral changes should begin as soon as possible to offset these problems. It can be difficult to change eating habits for anyone, but for an older HIV positive person it is critically urgent to do so to prolong one’s life.

For example, HIV positive people must consume more protein and break down the protein in their muscles at a faster rate than HIV negative people, which can lead to decreased muscles mass and strength, muscle wasting and immune suppression. Determining the right amount of food to eat can prevent undesired weight loss or gain. Obesity is a problem in this country. One reason is that as we age, we need less food, but we are programed to eat large portions and often of the wrong kind of food; i.e., food that is not nutritious, high in salt and sugars. It is often thought that weight loss is the big problem with HIV positive people, but weight gain is as much of a problem.

Also, as noted above, activities of daily living tend to decrease in HIV positive older people. Consequently, they may begin to not get out as often to shop for food or bother to prepare nutritious meals. Moreover, they may have financial problems, unstable housing, transportation problems, no food stores nearby, lack of access to proper food storage and suffer from “food insecurity” or lack of food. It is imperative that the food needs of the older HIV positive adult be frankly discussed and interventions made if needed. Many counties have a “meals-on-wheels” food program that delivers two nutritious meals each day. Enrolling such a program, if available, has the added benefit of the social interaction with the delivery person.

Finally, and needless to say, exercise is a crucial aspect of maintaining health at all ages, but even more so as one ages and even more than that for a person with HIV. A brisk walk everyday can lower triglyceride levels, alleviate depression, increase cardiac and pulmonary capacity, maintain muscle and bone health and contribute to a general sense of well being. The old adage of “use it or lose it” very much applies in this case. There may be exercise programs or equipment at senior centers, dance or Tai Chi or other low impact exercises that can help. Moreover, there is social interaction under those circumstances and helps with problems with isolation or despair.

CONCLUSIONS

Older people with HIV/AIDS face unique challenges as they grow older and use medications over decades or just begin a medication regimen. They have physical problems specific to their population due to the HIV virus and the medications they take and the living situation to which they are subject. Older people with HIV/AIDS have specific and often multiple co-morbid conditions that include heart, liver and kidney disease, metabolic disorders, non-AIDS related cancers, chronic inflammation and depression. Older people with HIV/AIDS appear to age faster than those without the disease and have increased mortality rates.

Older people with HIV/AIDS often suffer from substance abuse and a reduction in instrumental and basic activities of daily living and cognitive deficits.

A person growing old with HIV/AIDS can live well by being checked every three months by a physician, including having their blood and viral load checked. They can improve their quality of life by maintaining good dental hygiene, having a healthy diet and exercising.

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1 Academic Medical Center (AMC), Global Health, Amsterdam, Netherlands, 2 AmsterdamInstitute for Global Health and Development (AIGHD), Amsterdam, Netherlands,3 Academic Medical Center (AMC), Neurology, Amsterdam, Netherlands, 4AcademicMedical Center (AMC), Infectious Diseases, Amsterdam, Netherlands, 5 Public Health Service Amsterdam, Infectious Diseases Research, Amsterdam, Netherlands, 6 HIV Monitoring Foundation, Amsterdam, Netherlands

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A National Association of People Living with HIV/AIDS, Newtown, NSW 2042, Australia.

B Alfred Hospital, Melbourne, Vic. 3181, Australia.

C Melbourne Sexual Health Centre, Carlton, Vic. 3053, Australia.

D The University of Western Australia, Crawley, WA 6009, Australia.

E Royal Perth Hospital, Perth, WA 6001, Australia.

F The Kirby Institute for Infection and Immunity in Society, Darlinghurst, NSW 2010, Australia.

G Corresponding author. Email: Sean@napwa.org.au

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