- Non-AIDS Events
- The Consequences of Low-Level, Persistent HIV
- Aging and HIV and the Immune System
- Research Is Needed
As a result of tremendous community outcry for more attention to the topic of aging and HIV, Project Inform sponsored a forum on "The Consequences and Management of Aging and HIV" in September 2009. As anticipated, the San Francisco LGBT Center was packed as presentations on the clinical and psychosocial aspects of aging with HIV were presented. Steven Deeks MD UCSF, Peter Carnini MFT, New Leaf and Matt Sharp from Project Inform led the forum.
Our society is aging. Baby boomers are reaching their senior years and the impact on our health care infrastructure is being felt. In California, half of the state's population will reach 65 years old or older in the next ten years.
Due to the success of antiretroviral therapy, people with HIV are also living longer and into their senior years. Today in the UK, nearly one-third of people with HIV are more than 45 years old. In the US, it's predicted that by 2015 half of people with HIV will be over 50. In San Francisco, 27% of people with HIV were over 50 in 2003, but by 2008 40% were older than 50. This growing number will impact social service delivery and affect our already fragile health care system. Providers are generally not sensitive to the concerns and needs of an aging HIV population.
Fifteen percent of newly diagnosed people with HIV are over 50 years old. Since this population is mostly heterosexual, it raises many concerns over the lack of targeted prevention for older people in a society that stigmatizes them as a population of people who don't or shouldn't have sex.
The remaining aging population has been on HIV treatment for a long time and is generally healthier, having returned to work or at least maintained a reasonable quality of life. We know that the cumulative survival rate is going up due to this success, but it is also an odd paradox that many who have been successfully treated and reached undetectability are also now at increased risk for certain diseases commonly seen in the elderly.
The fact remains that life expectancy is lower for those who started HIV treatment late or their CD4 cells never increased as a result of therapy. The Antiviral Therapy Collaborative Cohort Study showed life expectancy has increased due to therapy but has not reached the same level seen in the HIV-negative population. Our work is cut out for us.
The physical effects of aging are well known. However, the consequences of aging and HIV are interrelated. But it is still not completely understood if HIV causes premature aging or if aging makes HIV disease worse. Researchers are looking for answers in ongoing and planned laboratory and clinical research.
Today, a third or more of deaths most common in older people with HIV are not caused by AIDS. Most of these clinical issues are known as non-AIDS events, which are illnesses not related to HIV. These events are also being seen more often than in the earlier days of the epidemic. Before HAART, the biggest cause of mortality was due to opportunistic infections in people with severe CD4 loss. Non-AIDS events such as cardiovascular disease and malignancies are most often caused by direct viral infection, a sub-optimal CD4 response to therapy and by inflammation.
Despite effective HAART, there remains a low level of latent virus that leads to inflammation which causes some of the non-AIDS events such as heart disease. Also, many of the non-AIDS conditions are also common in older people in general, so as HIV+ people grow older the risks become greater.
Heart disease has long been a concern in HIV, and especially in recent years as the HIV population ages and cumulative data on different markers for heart disease, including heart attacks, are growing. Heart disease is the most important cause of death in the general population and is higher in people with HIV. Heart attack risk is increased with Ziagen or Epzicom although the reason has not been established. Protease inhibitors increase lipids that are associated with heart disease, however newer drugs may be less of a problem. Other lipid-friendly regimens exist, so providers should individualize therapy based on risk factors for heart disease.
More long-term research is needed in people with HIV to understand the cumulative effect of HIV therapy as they grow older.
The liver is the body's critical filtering mechanism. It makes sense that, over time, the liver wears down, especially in co-infection with HIV and hepatitis B or C. Inflammation and low CD4s are related to liver disease. In aging populations of people with HIV alcohol, obesity and poly-pharmacy, or the use of many drugs together, are also factors related to liver disease.
AIDS-related cancers such as non-Hodgkins lymphoma and Kaposi's sarcoma have declined in the HAART era. However, most malignancies occur as people age, and as time passes older people with HIV will be at a higher risk for cancer. In HIV, Hodgkins lymphoma, anal, throat, liver and head and neck cancers are the most common malignancies. These cancers are most often caused by an infectious agent such as hepatitis B or C, or human papillomavirus. Low CD4 cells and inflammation are also related. Today, AIDS dementia is also less common due to HAART because neurocognitive decline is greatly slowed with effective HAART. But some are concerned that many effective HIV drugs do not penetrate the central nervous system, which may lead to mild neurocognitive symptoms that are quite common in older people with HIV. Alzheimers disease and senility have been a big concern in the general aging population, but persistent HIV and inflammation are contributing to these already debilitating and frustrating conditions in older people with HIV.
Bone fractures and osteoporosis (loss of bone density) are also common in older people. Yet, osteoporosis is three times higher in people with HIV. Osteopenia (thinning of the bone mass) is even higher. Long-term HIV disease, inflammation and non-HIV related factors such as alcohol use are all risks to good bone health in older people with HIV. There has been some concern regarding Viread (tenofovir) causing bone disease, however this has not been borne out in studies thus far. Doctors suggest using vitamin D supplements and calcium where appropriate.
Frailty is characterized as unintentional weight loss, exhaustion, low physical activity, weakness and slowness. It includes poor general health, risk of falling, poor appetite, loss of muscle mass and bone demineralization. It is a common geriatric condition but is now being seen in older people with HIV. Again, persistent inflammation and low CD4 counts are related to this condition.
Despite effective treatment, HIV persists in small amounts (millions of copies) in various "reservoirs" in the body where it can lay silent in cells that are "asleep." These cells must be activated to release new virus, which in turn starts a normal immune response. Since this is an ongoing low-level response, inflammation can remain as long as virus is present. This low level is not detected by standard tests, but researchers detect it in highly sensitive assays that reach below 1 copy.
Viral proteins released by this persistent virus in the latent reservoir can be toxic to the body and also cause immune activation. HIV persistence is being researched and may lead to what is being called "functional cure."
Inflammation is a normal immune process involving specific cells and cytokines that in HIV are switched on due to chronic immune responses (either due to sub-optimal treatment or low level persistent HIV). Inflammation does decrease w/ HAART but never returns to normal.
A process called microbial translocation is seen within a few weeks of HIV infection and can weaken a person's immune capacity, possibly never being fully restored. After infection, HIV targets CD4 cells in the gut, demolishing a large part of the body's important immune reserves. Then, bacterial microbes travel outside of the gut and enter the bloodstream where the immune system responds to them, activating T cells that are infected with HIV. More HIV is produced leading to further immune damage. This is one of the most important physiological reasons for stopping virus as soon as possible after infection.
As we grow older certain aging processes are similar to what chronic HIV does to our bodies. Apoptosis is our natural mechanism to rid our bodies of unnecessary, weak or damaged cells. Apoptosis can lead to suppression of the immune system which can also lead to cancers. It is a process that most likely occurs more often in older people with HIV.
HIV damages lymph node structure and thymic dysfunction, and there is a cumulative effect as people with HIV grow older. Over long-term HIV infection, the thymus loses its function and fewer crucial T cells are produced, causing low CD4 and CD8 ratios and low memory to naive cell ratios. This leads to further immune system damage.
Another process that becomes dysregulated in aging and HIV is called immunoscenecence. This is another word for "immunologic aging" or "exhaustion" of T cells. This can cause a destructive high T cell turnover and may be part of premature "aging" of the immune system.
In HIV disease and in older people the immune system's functional capacity decreases. This is what causes a poor response to vaccines and the TB skin test. Oxidative stress occurs in both the elderly and people with HIV. Over time this can create further suppress the immune system.
Although we have made huge progress with HIV therapy, the effects of living longer with HIV despite viral control are still not completely understood. It is clear that this issue requires more research, although it's hard to know if there will be clear answers anytime soon. There are still many unknowns in HIV pathogenesis, technical laboratory issues, new assays needing development and clinical studies will be challenging to design and recruit. Much that scientists are learning about aging and HIV is daunting and most of the news is sobering. Yet people with HIV are gaining years on their lives, and surviving despite critical odds. People with HIV can maintain health through a few practical management tips such as monitoring for and treating underlying cardiovascular disease, screening and reducing risk for cancers, individualizing HIV treatment, appropriate exercise, healthy diets and stress reduction. Importantly, research is promising on immune related therapies and better, less toxic HIV drugs that have the potential to take us into a different paradigm of living with HIV.