Aging and the HIV Patient: A Lecture With Powderly, MD

[Guest guest]

http://www.medscape.com/viewprogram/8867_pnt

Editor's Note: As the HIV epidemic matures, so too do the patients we treat with the disease; as is now said, HIV has become one of the noncurable but manageable chronic conditions in adulthood. As we will hear from Dr. Powderly, the aging face of HIV brings new challenges as increasing age also brings well-known associated conditions. In particular, the risk for cardiovascular disease and cancer is an important consideration in the HIV-infected patient as he or she ages. In addition, the immune system naturally declines with age and the consequence of that for HIV infection is not yet clear.

Dr. Powderly will take the viewer through the epidemiology of HIV in an aging population. Partially due to improved antiretroviral therapy (ART), the prevalence of HIV in people over 50 is increasing. However, older people are being diagnosed with HIV as a primary infection acquired in older age. Most of the prevention messages that have been developed are focused on a younger population; in many cases the messages about safer sex and avoidance of risk behavior were not directed to older adults. As a consequence, HIV infection is often underdiagnosed in older patients and thus they are more likely to present with an AIDS-related illness rather than asymptomatic HIV infection.

Further, this program will address the interplay of these 2 conditions -- HIV infection and aging -- both of which are associated with a decline in immunocompetence and immune surveillance. Is there an interplay of the two and could the result be additive? In his discussion of the natural history of HIV in older patients, Dr. Powderly acknowledges that the data are not clear. In the era before effective ART, it appeared that immune system decline was more rapid in HIV-infected patients who were older, particularly those older than 50. In spite of the feeling that response to treatment might not be as effective as in younger patients, it appears that older patients may be more likely to have a suppressed viral load after treatment vs younger patients; this could be related to adherence -- ie, that older patients are actually more likely to be adherent to medication and, as a consequence, have a better antiviral response.

As this program points out, it does appear that older patients have a slower CD4 count recovery and may not reach the same levels of CD4 cells as younger patients when given effective ART. Whether that has a long-term effect and whether it will lead to a greater degree of subtle immunodeficiency as patients age is as yet unknown, but this certainly should be considered in terms of the timing of therapy and whether it will be possible to have a better immunologic recovery if patients are treated at a younger age.

One of the most important issues in the older HIV-infected patient is the question of increased risk for comorbidities. As Dr. Powderly discusses, all aging patients are at increased risk for comorbid conditions such as cardiovascular disease, metabolic syndrome and frank diabetes, changes in body composition, renal deterioration, osteoporosis, and malignancy. Does HIV infection accelerate the aging process, making these conditions more likely and of earlier onset? And, equally, does HIV treatment accelerate these conditions? It is clear from Dr. Powderly's analysis of the D:A:D study that the traditional risk factors for coronary heart disease, in particular age, are most important in the HIV-positive population. In contrast, the risk for ART is, in fact, quite small compared with traditional risk factors. The reality is that most patients who sustain myocardial infarction or cardiovascular disease as a result will do so because of traditional risk factors and not because of HIV-related risk factors.

It is our hope that this program on the interplay of HIV infection and aging -- the epidemiology, the impact of delayed diagnosis, the confluence of 2 immunosuppressive conditions, and the importance of associated comorbidities -- will further the recognition and improve the treatment of patents in an HIV epidemic that is aging.

This activity is supported by an independent educational grant from Gilead Sciences.

Aging and the HIV Patient: A Video Lecture With Powderly, MD (Slides with Transcript)

Editor's Note: As the HIV epidemic matures, so too do the patients we treat with the disease; as is now said, HIV has become one of the noncurable but manageable chronic conditions in adulthood. As we will hear from Dr. Powderly, the aging face of HIV brings new challenges as increasing age also brings well-known associated conditions. In particular, the risk for cardiovascular disease and cancer is an important consideration in the HIV-infected patient as he or she ages. In addition, the immune system naturally declines with age and the consequence of that for HIV infection is not yet clear.

Dr. Powderly will take the viewer through the epidemiology of HIV in an aging population. Partially due to improved antiretroviral therapy (ART), the prevalence of HIV in people over 50 is increasing. However, older people are being diagnosed with HIV as a primary infection acquired in older age. Most of the prevention messages that have been developed are focused on a younger population; in many cases the messages about safer sex and avoidance of risk behavior were not directed to older adults. As a consequence, HIV infection is often underdiagnosed in older patients and thus they are more likely to present with an AIDS-related illness rather than asymptomatic HIV infection.

Further, this program will address the interplay of these 2 conditions -- HIV infection and aging -- both of which are associated with a decline in immunocompetence and immune surveillance. Is there an interplay of the two and could the result be additive? In his discussion of the natural history of HIV in older patients, Dr. Powderly acknowledges that the data are not clear. In the era before effective ART, it appeared that immune system decline was more rapid in HIV-infected patients who were older, particularly those older than 50. In spite of the feeling that response to treatment might not be as effective as in younger patients, it appears that older patients may be more likely to have a suppressed viral load after treatment vs younger patients; this could be related to adherence -- ie, that older patients are actually more likely to be adherent to medication and, as a consequence, have a better antiviral response.

As this program points out, it does appear that older patients have a slower CD4 count recovery and may not reach the same levels of CD4 cells as younger patients when given effective ART. Whether that has a long-term effect and whether it will lead to a greater degree of subtle immunodeficiency as patients age is as yet unknown, but this certainly should be considered in terms of the timing of therapy and whether it will be possible to have a better immunologic recovery if patients are treated at a younger age.

One of the most important issues in the older HIV-infected patient is the question of increased risk for comorbidities. As Dr. Powderly discusses, all aging patients are at increased risk for comorbid conditions such as cardiovascular disease, metabolic syndrome and frank diabetes, changes in body composition, renal deterioration, osteoporosis, and malignancy. Does HIV infection accelerate the aging process, making these conditions more likely and of earlier onset? And, equally, does HIV treatment accelerate these conditions? It is clear from Dr. Powderly's analysis of the D:A:D study that the traditional risk factors for coronary heart disease, in particular age, are most important in the HIV-positive population. In contrast, the risk for ART is, in fact, quite small compared with traditional risk factors. The reality is that most patients who sustain myocardial infarction or cardiovascular disease as a result will do so because of traditional risk factors and not because of HIV-related risk factors.

It is our hope that this program on the interplay of HIV infection and aging -- the epidemiology, the impact of delayed diagnosis, the confluence of 2 immunosuppressive conditions, and the importance of associated comorbidities -- will further the recognition and improve the treatment of patents in an HIV epidemic that is aging.

Slide 1. Introduction Slide

Bill Powderly, MD: I'm Dr. Bill Powderly, Head of the School of Medicine and Medical Science at University College Dublin in Ireland. I'm going to be presenting today on the topic of aging and the HIV-positive patient.

Slide 2. Aging and the HIV-Infected Patient

Introduction

My talk will cover a number of aspects, including the epidemiology of the interaction between HIV and aging, the natural history of HIV in older patients and their response to antiretroviral therapy, the issue of age and comorbidities -- that is, the diseases that increase in frequency as people get older -- and finally issues related to management of the HIV-positive patient as he or she gets older.

We will now pause for a polling question.

In your practice, what percentage of HIV-infected patients are over 50 years of age?

< 10%

10%-20%

20%-30%

30%-40%

> 40%

Slide 3. Epidemiology

Epidemiology of HIV and Aging

In terms of the epidemiology, it's clear that the number of patients with HIV in the older age group has been increasing over the last 10 years. This is a reflection of a number of important considerations. The first is that with the success of antiretroviral therapy, people are surviving and they're surviving now well into their fifties and sixties -- which is obviously a good thing, but nonetheless brings on the complications that are associated with older age.

But in addition, older people are being diagnosed with HIV as a primary infection or a first infection that is actually acquired in older age. The issue of older people with HIV brings new challenges. Age is associated with other diseases. In particular, the risk for cardiovascular disease and cancer are important interactions with the HIV-positive patient as he or she ages. In addition, the immune system naturally declines with age and the consequence of that for HIV infection is not yet totally clear.

Slide 4. Primary Transmission in HIV

Primary Transmission in HIV in Older Adults

There are a number of issues related to primary infection in HIV-infected older age patients. The issue is related to the fact that most of the prevention messages that have occurred and been developed in the last 20-25 years are largely focused on a younger age population. So in many cases, the messages about safer sex, the messages about avoidance of risk behavior, are not directed to older adults.

In addition, major social changes have occurred in the last 20-30 years that increase the possibility of exposure for older adults. Increasing divorce rates and the wider use of impotence treatments have clearly highlighted the fact that adults, as they get older, remain sexually active. And as a consequence, HIV infection is often underdiagnosed and underappreciated in older patients.

Slide 5. Primary Transmission in HIV

This has a number of important consequences. The first is that clinicians are less likely to think about HIV and AIDS when patients at an older age present with an unusual illness. As a consequence of that, delayed diagnosis, the patients are more likely at an older age to present with an AIDS-related illness rather than just HIV infection itself.

Furthermore, clinicians are less likely to discuss HIV/AIDS, its avoidance, its risk factors, and even the possibility of needing an HIV test with older individuals. And in general, the routine testing for HIV infection is focused on a younger population. So older patients are less likely to have access to such routine testing.

We will now pause for a polling question.

In your experience, which of the following poses the greatest challenge in treating patients with HIV and advancing age?

More difficult viral control/resistance issues

Worsening immune deficiency/falling CD4 counts

Metabolic syndrome/diabetes mellitus

Body composition changes

Lipid abnormalities and/or cardiovascular complications

Slide 6. Age and Natural History of HIV

Natural History of HIV in Older Patients

When one thinks about the natural history of HIV, one recognizes the fact that the immune system declines with HIV infection. We all are too familiar with the consequences of untreated HIV leading to a waning of the immune system and an increased risk for opportunistic infections, opportunistic malignancies, and death -- in other words, the natural history of untreated HIV infection.

Is there an interplay with age? Well, it isn't completely clear. However, data in the era before effective antiretroviral therapy have suggested that the immune system decline is more rapid in HIV-infected patients who are older, particularly those older than 50. Furthermore, initially with antiretroviral therapy, there was a fear or concern that the response to treatment might not be as effective as in younger patients.

The data are mixed. It's very clear that in general the immune response to antiretroviral treatment in older patients is less rapid than in those who are younger. However, they also appear to have a better response to antiretroviral therapy; that is, older patients in some cohort studies are more likely to have a suppressed viral load after treatment than younger patients. Some recent studies, particularly from the Kaiser cohort in California, have suggested that that might be related to adherence -- that older patients are actually more likely to be adherent to medication and, as a consequence, have a better antiviral response.

Slide 7. Cumulative Mortality Rate for Patients Who Were Not Exposed to ART, According to Age Group (<50 vs >50)

This slide shows data from the s Hopkins cohort, looking at the mortality in patients who were not exposed to antiretroviral therapy. You can see in this slide that older patients were more likely to die and had a more rapid disease progression than younger patients if treatment was not available.

Slide 8. Cumulative Mortality Rate for Patients Who Were Exposed to ART, According to Age Group (<50 vs >50)

However, when one looks only at people who were exposed to effective antiretroviral therapy, this effect of age disappeared, suggesting that older patients will respond to antiretroviral therapy from the perspective of clinical progression as well as younger patients.

Slide 9. Influence of Age on CD4 Cell Recovery

Now in terms of immunologic progression, it does appear that older patients have a slower CD4 count recovery and may not reach the same levels of CD4 cells as younger patients do when given effective antiretroviral therapy. Whether that has a long-term effect, whether it will lead to a greater degree of subtle immunodeficiency as patients get older, is as yet unknown; but it is certainly something to consider in terms of the timing of antiretroviral therapy and whether it will be possible to have a better immunologic recovery if patients were treated at a younger age compared with those treated at an older age.

Slide 10. Age and Comorbidities in HIV Infection

Age and Comorbidities in HIV Infection

One of the most important issues in the older HIV-positive patient is the question of increased risk for comorbidities. As we all get older, our risk for important diseases, such as cardiovascular disease and heart disease, such as diabetes, such as osteoporosis and kidney disease, and particularly cancer, increases with age. There has been a lot of speculation and some concern as to whether HIV infection changes the dynamics of those comorbidities.

Does [someone's HIV infection] accelerate the aging process, make it more likely that they will get some of these comorbidities at an earlier age than they would have if they were not HIV-infected? And equally, does HIV treatment accelerate these cardiovascular diseases?

We will now pause for a polling question.

In your clinical experience, which of the following is the strongest risk factor for cardiovascular disease in your patients with HIV infection?

The HIV infection itself

Antiretroviral therapy for HIV infection

Patient age

Patient family history of cardiovascular disease

History of or current smoker

Slide 11. Cardiovascular Risk Increases With Age

Cardiovascular Disease

Cardiovascular disease is one that is particularly associated with increasing age. There are certain risk factors for cardiovascular disease that are unchangeable. They are: being a man, a family history, and age. This particular slide shows the risk calculation scores from the National Cholesterol Education Program showing identical risk factors in 2 men, one at the age of 45 and the other at the age of 65.

You can see that with everything else being the same, the risk of developing cardiovascular disease, particularly myocardial disease, in the next 10 years for the 45-year old man is 6%, whereas for the 65-year old man with identical risk factors, it is 21%. This is a very important consideration when one looks at the interaction between HIV and HIV treatment and age.

Slide 12. Prevalence of Most Coronary Risk Factors Rises With Age

The other important understanding is that the prevalence of most of the important coronary risk factors also increases with age. Now, this increased prevalence of coronary risk factors may be a major factor as to why age itself is associated with an increased risk for coronary heart disease. But it is important to realize that in particular, diabetes, shown in the middle panel, and hypertension become much more common as people get older. So their contribution to heart disease becomes more and more important as the population ages.

Slide 13. DAD Study: Impact of Traditional Risk Factors for CHD

If one takes one of the most well-known cardiovascular risk studies from the HIV population, the D:A:D study, one can see very clearly that the traditional risk factors for coronary heart disease are very important in the HIV-positive population. In particular, if one looks at the highlighted effect of age, you can see that for each additional 5 years the risk of developing a myocardial infarction increases by 39%. That is comparable to family history and of less importance only to having a prior heart event or being a smoker.

In contrast, the risk for antiretroviral therapy (although clearly measurable and now well recognized, particularly for protease inhibitors), is, in fact, quite small compared with these traditional risk factors. So although these are relative risk factors, the reality is that most patients who develop myocardial infarction or cardiovascular disease as a result, while they're HIV-positive, will do so because of traditional risk factors and not because of HIV-related risk factors.

Slide 14. Metabolic Syndrome: Prevalence in Treated HIV+ Patients and Controls

Metabolic Syndrome and Diabetes Mellitus

Similarly, there has been a lot of attention paid to the prevalence of metabolic syndrome in HIV-infected patients. There has been some suggestion that HIV-infected patients, particularly those on certain treatments, may be more likely to develop the metabolic syndrome, which is of itself a recognized risk factor for developing a cardiovascular disease. However, one of the disadvantages of many studies that have come out looking at this issue is that they have not been well controlled. If one includes age- and gender-matched controls, one sees that, in fact, the prevalence of metabolic syndrome in HIV-infected patients is quite similar to that in the control population.

One of the most striking and independent predictors of the risk for metabolic syndrome, whether patients are HIV-positive or negative, is age. As I noted previously, the risk for diabetes mellitus in particular increases with age and probably contributes to the effect of age on the risk for cardiovascular disease.

Slide 15. Body Composition And Age

Body Composition Changes

Similarly, there has been a lot of attention given to the changes in body composition associated with HIV infection -- the loss of subcutaneous fat (or lipoatrophy) and fat accumulation or (lipohypertrophy). It's worth pointing out, however, that age itself also affects body composition and, as a consequence, there is an important interaction that needs to be considered. It is increasingly clear that lipoatrophy is a complication of antiretroviral therapy, particularly thymidine analog drugs, but is more likely to occur in the older patient.

Similarly, lipohypertrophy is a factor of getting older. Patients who are HIV-positive can have a combination of both lipoatrophy and lipohypertrophy, whereas HIV-negative patients tend to have truncal fat accumulation -- in other words, a middle age spread as they get older.

Slide 16. Prevalence of Chronic Kidney Disease in the General Population Increases With Age

Renal Dysfunction

There has been considerable attention paid to the issue of renal disease in HIV-positive patients. What is sometimes overlooked is the fact that renal function deteriorates with age. This slide shows you that whether one measures renal function as a change in GFR [glomerular filtration rate] at a 50% decrease or at a larger decrease, the risk of developing significant renal dysfunction increases as patients get older. So once again, it is very important when considering changes in HIV-infected patients to also account for age before ascribing any causation to HIV or its treatment.

We will now pause for a polling question.

In regard to loss of bone mineral density, have you noted osteoporosis in your patients with HIV infection and do you screen for this complication?

I have not seen in my patients and do not screen for this complication

I have not seen in my patients but do screen for this complication

I have seen in my patients but do not screen for this complication

I have seen in my patients and do screen for this complication

Slide 17. Osteoporosis and AIDS

Bone Disease

A very similar issue applies to the loss of bone mineral density in patients with HIV infection. Many cohort studies summarized in this particular slide have shown an increased prevalence of reduced bone mineral density in HIV-infected patients. This appears to be a greater prevalence than one would expect in HIV-negative patients.

However, we have much more to learn about osteoporosis and bone mineral density loss in HIV-infected patients. One of the most important things is whether this point prevalence, which is clearly increased, is reflected over time.

Slide 18. BMD Decreases With Age

It is very, very clear -- and this slide shows you data from normal populations -- that the peak bone mineral density occurs around the age of 30 and decreases inevitably in everybody over time. It's more accelerated in women, particularly around the time of menopause. But as you can see, both men and women lose bone inexorably as they get older.

What is unclear from an HIV-positive perspective is how this translates to an increased risk for the complications of osteoporosis -- that is, fractures and immobility as people get older. It is going to be a very important research issue in the next 10-12 years.

Slide 19. Invasive Cancer Incidence Increases by Age

HIV And Malignancy

Finally, in terms of the comorbidities, we should address the issue of cancer. Again, the incidence of cancer increases as we get older. This is US data from the Centers for Disease Control and Prevention showing very clearly the relationship between age and the incidence of cancer. In HIV-positive patients, it is not yet clear whether there is a relationship between being HIV-positive and developing cancer.

Slide 20. HIV And Malignancies

Again, the D:A:D cohort shows that HIV-infected patients are now more likely to die from non-AIDS-related malignancies than they are from the traditional AIDS-related malignancies, such as Kaposi's sarcoma and lymphoma. However, it is unclear whether the fact that they are dying of these cancers is at all related to their HIV infection or merely a reflection of aging. Again, only time will allow us to dissect the interaction between HIV and malignancies.

Slide 21. Antiretroviral Tolerability Decreases With Age

Management Issues in Older Patients

We'll talk for a few moments on the issue of management of the older patients. One of the interesting things is that the ability to tolerate antiretroviral therapy decreases with age. This shouldn't be too surprising because drug toxicities in general, whether we're talking about anti-HIV drugs or any other drug, increase as patients get older.

What is shown in this particular slide is data from the Kaiser Permanente cohort in Northern California, which clearly shows that the risk of developing a toxicity is significantly increased in patients as they get older. Looking at patients who are 50 or older compared with patients who are 30 or younger, the risk of having high cholesterol, the risk of having diabetes, or the risk of having an increased creatinine after starting antiretroviral therapy was significantly different in the older patients.

Slide 22. Management Issues in Older HIV-Infected Patients

What does this mean for management? There are certain specific issues that we need to think about. The first is what therapy should be used in an older patient? In general, there's no evidence that any particular drug is better in an older patient than a younger patient. But we have to keep in mind the comorbidities. And if there are therapies that are associated with an increased risk for certain comorbidities, then they should be, if possible, a second choice or avoided in older patients.

It's also critical to recognize that as patients get older, it's important for clinicians to think about their regular clinical management and that, as a consequence, general health screening and cancer screening should be done as if the patients were HIV-negative. One has to be aware of drug-drug interactions and the issues of polypharmacy and recognize that HIV-positive patients in certain circumstances may not respond as well to routine therapy.

Slide 23. Management of Dyslipidemia in the HIV-Infected Population May Be Less Effective Than in HIV-Negative Patients

This particular slide is data from the Veterans Administration, which shows that patients who receive antilipid therapy who are HIV-positive respond less well than HIV-negative patients. You can see right across the slide that the likelihood of having an effective response to lipid-lowering therapy was lower in HIV-positive patients. This may reflect the choice of drugs. Certain statins are contraindicated in patients who are HIV-positive because of drug interactions, particularly with the protease inhibitors, and so clinicians may be choosing less potent drugs as a consequence in HIV-positive patients.

Slide 24. Summary

Conclusion

To conclude, the prevalence of HIV infection and AIDS itself is increasing in patients over the age of 50. This reflects both improved survival and continued primary infection. Older patients are more likely to present late because clinicians may not think about the diagnosis. As a consequence, the benefits of early antiretroviral therapy may be lost in older patients.

Older patients do respond well, perhaps because they're more likely to be adherent, although their immunologic response may not be as robust as those in younger patients. Management of the older HIV-infected patient is complicated by the fact that age increases their risk for common comorbidities, cardiovascular disease, cancer, diabetes mellitus, renal disease, and bone disease.

Whether HIV itself or the antiretroviral therapy that we give patients also increases the risk for these comorbidities is still unclear, but it certainly points to the fact that patients need to be monitored for these comorbidities. They need to be appropriately managed with consideration to the type of HIV therapy that is given to avoid making these comorbidities worse or [introducing] drug interactions that would complicate management.

This is a problem that is not going to go away. The success of antiretroviral therapy makes it inevitable that our patient population will get older. This is something to be applauded but also something to be tackled proactively.

This activity is supported by an independent educational grant from Gilead Sciences.

Authors and Disclosures

The material presented here does not necessarily reflect the views of Medscape or companies that support educational programming on www.medscape.com. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.