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HIV, Ageing and Comorbidities

Health conditions among adults growing older with HIV

The medical response to HIV in adults has changed. Whilst in the early days of the global HIV epidemic treatment for people living with HIV focused on treating opportunistic infections, minimising pain, and providing palliative care, today medical management of HIV includes addressing premature ageing, comorbidities, drug-interactions and other non-AIDS related complications.

The following outlines the main health problems that have been identified among adults who are growing older with HIV.

The heart

A heart graphicCardiovascular disease, or CVD, refers to a group of diseases that affect the heart or blood vessels. Cardiovascular-related events are the main cause of death worldwide; in 2008 CVD accounted for 30 percent of global deaths. 1 Among the HIV-positive population, CVD is also one of the primary causes of mortality.

Three main factors have been identified that increase an HIV-positive person’s risk of CVD:

  • Traditional risk factors. These include older age, gender (male), smoking, lack of exercise, high blood pressure and high cholesterol. Studies show that the prevalence of some risk factors, such as smoking, is high among people living with HIV. 2
  • HIV infection. The virus itself is thought to contribute to a greater risk for CVD (independent of the traditional risk factors), due to its association with a chronic inflammatory state. 3 4
  • Antiretroviral therapy. Some studies have reported an association between certain antiretroviral drugs and an increased risk of CVD. For example, in one study indinavir, lopinavir-ritonavir, didanosine and abacavir were associated with an increased risk of heart attack. However, authors reiterated that the results should be interpreted in the context of the benefits that these drugs provide. 5

Bones

A bone graphicOsteoporosis, a common bone disorder, typically affects adults as they grow older. The disease is characterised by a low bone mineral density (BMD), which can lead to an increased risk of bone fractures. Although osteoporosis is primarily found among post-menopausal women, the disease has increasingly been found among both men and women of all ages living with HIV. In the United States for example, one study found the prevalence of osteoporosis more than three times greater among HIV-positive individuals compared with HIV-negative study participants. 6 Another study saw the rates of fracture among HIV-positive persons increasing, whilst fracture rates decreased among the general population. 7

Low BMD in HIV-positive people may be a result of a number of factors that are associated with HIV infection, such as low body weight, malnutrition and vitamin D deficiency. Traditional risk factors for osteoporosis, such as gender, increased age, smoking and injecting drug use, may also contribute to low BMD among those living with HIV. 8

It has also been suggested that both long-term HIV infection and antiretroviral drugs contribute to a lower bone mineral density. 9 10 One study found that, among patients receiving continuous antiretroviral therapy, BMD steadily declined, compared to the patients receiving intermittent, CD4 cell count-guided antiretroviral therapy, whose BMD remained stable or increased. 11

The Brain

A brain graphicIt is generally understood that neurocognitive disorders among people living with HIV are associated with: 12

  • HIV infection
  • Ageing
  • Antiretroviral treatment

The effects of HIV-infection on the brain are referred to as HIV-associated neurocognitive disorders (HAND). The presence of HAND are determined through a cognitive assessment and reports of everyday functioning decline by patients. Neurocognitive impairments may affect many aspects of a persons everyday function abilities, including – the ability to process information quickly, the ability to learn or remember, their motor and executive functions, and their working memory. ‘HAND’ vary in both type and severity and can occur at any stage of HIV infection: 13

  • Asymptomatic neurocognitive impairment. Neurocognitive impairment has been detected by cognitive tests, but there is no impact on the person’s everyday functioning abilities.
  • Minor neurocognitive disorder. Neurocognitive impairment has been detected, and has a significant impact on the person’s everyday functioning abilities.
  • Severe HIV-associated dementia. 14 The person experiences extreme difficulty with many of the everyday function abilities, listed above.

The overall incidence of HAND has declined since highly-active antiretroviral therapy (HAART) became available; this more effective form of treatment significantly lowers HIV viral levels in the body, reducing the effect of HIV on the brain. HAART also reduced incidences of opportunistic infections, such as toxoplasmosis and cryptococcal meningitis, that negatively affect the brain. 15 Most evident when comparing the pre-and post-HAART eras is the decline of severe HIV-associated dementia cases among people with HIV; from 7 percent in 1989 to 1 percent in 2000. 16 17

Whilst antiretroviral treatment has reduced the effect of HIV on the brain, some antiretroviral drugs cannot pass through the blood-brain barrier; this is the cells and membranes controlling what passes in and out of the brain. 18 Depending on how well antiretroviral treatment penetrates through the blood-brain barrier, HIV viral load can remain detectable and continue to replicate in the brain, even when HIV is undetectable in the body. HIV-infection in the brain can cause neurocognitive damage and explains why HAND remains common among people living with HIV. 19 Furthermore, whilst antiretroviral drugs are becoming less toxic, some can have a negative-effect on the brain, which may also contribute to the prevalence of less severe neurocognitive disorders, such as asymptomatic and minor neurocognitive impairments.

As an individual with HIV ages, the risk of neurocognitive conditions increases, as is the case among the general ageing population. 20 Age-related neurocognitive conditions include, Alzheimer disease, Vascular dementia and Parkinson disease-related dementia. Other age-related conditions, such as diabetes or hypertension, have also been found to amplify the effects of neurocognitive conditions in people with HIV. 21

Cancer

Cancer cells graphicCancer is the rapid growth of abnormal cells in the body and can be caused by a number of factors. Cancer is found in many parts of the body; breast, prostate and lung cancer were most frequently reported worldwide among men and women in 2008. 22 Whilst cancer can often be cured it is still a leading cause of death worldwide, with 7.6 million deaths due to cancer in 2008. 23

HIV-positive people are more at risk of developing some cancers. For example, one study based in Denmark showed how people living with HIV were twice as likely to get cancer than the general population. The risk was higher for smoking related and virological cancers which are associated with a weaker immune system. By comparison, the risk of other cancers was found to be the same among both HIV-positive and HIV-negative people. 24

Another study actually found a 27 percent reduced risk of prostate cancer among HIV-positive men compared to HIV-negative men. Those HIV-positive men who did develop prostate cancer were more likely to have localised and less advanced cancer than the HIV-negative men. Regardless of HIV status, the risk of prostate cancer increased with age. 25

However, there are a number of factors that may contribute to the increased risk of certain cancers; however, research is ongoing and often contentious. Some of the major cancers that HIV-positive people are at an increased risk of developing include lung cancer, Karposi Sarcoma, Hodgkin lymphoma, anal cancer, liver cancer and non-melanoma skin cancer. 26 The risk of developing cancer varies between people, depending on factors such as access to treatment and exposure to cancer-causing factors.

The cancers that are common among people living with HIV can be divided into two categories, AIDS-defining cancers and non-AIDS-defining cancers, see below.

Most of the available data on cancer among HIV-positive individuals is from high-income countries. 27 Therefore, the discussion below is largely based on individuals living in a high-income setting.

AIDS-defining Cancers (ADCs)

AIDS-defining cancers (ADCs) are cancers that are often reported among people living with HIV, who do not have access to treatment. ADCs are typically associated with the progression to AIDS. People living with HIV are more likely to develop AIDS-defining cancers than HIV-negative individuals. 28 The WHO outlines 4 clinical stages in the progression from HIV to AIDS. 29 Kaposi Sarcoma and Non Hodgkin's lymphoma are two of the main cancers, referred to as AIDS-defining cancers (ADCs), found in some HIV-positive patients considered to be at WHO clinical stage 3 or 4. A person infected with HIV will progress to AIDS (clinical stage 3 and 4), if they do not take antiretroviral treatment, or if the treatment they take does not work because of drug resistance.

In countries where access to antiretroviral treatment is largely universal, the incidence of ADCs has declined significantly compared with the pre-ART years. 30 31 32 33 34 Nevertheless, where antiretroviral treatment is widely unavailable, AIDS-defining cancers remain a serious concern for people with HIV. 35

Non-AIDS-defining Cancers (NADCs)

Non-AIDS-defining cancers (NADCs) are cancers that are often reported among people living with HIV, but are not typically associated with the progression to AIDS. The incidence of NADCs has increased in recent years and the incidence of some NADCs is many times higher among HIV-positive people. 36
37 38 This has been attributed to a number of factors 39, such as viruses, HIV infection, antiretroviral treatment, and behavioural factors.

  • Cancer causing viruses. Evidence shows that some non-AIDS-defining cancers are associated with certain infectious viruses. 40 For example, infection with hepatitis B and C has been linked with liver cancer. 41 Also, infection with Human Papillomavirus has been linked with cancer of the anus and genitals. 42 43 44 Prevalence of these cancer-causing viruses is often high among HIV-positive individuals. 45 46

  • Smoking is associated with the development of cancerBehavioural factors. One behavioural factor that carries a cancer-risk is smoking tobacco. The prevalence of smoking tobacco is high among HIV-positive individuals. 47 Evidence suggests that HIV-infection actually increases the risk of cancer from smoking tobacco. 48 49 50 This may somewhat explain the increased risk of HIV-positive individuals developing lung cancer. 51 52 53 54 55 Other cancer-causing behavioural factors reported among HIV-positive individuals include alcohol abuse and chronic exposure to UV light from the Sun. 56 57

  • HIV infection. HIV infection can cause conditions usually found among the ageing population, 58 which cause cells to become exhausted at an earlier age; notably immunosuppression and inflammation. 59 These conditions speed up the body’s ageing process, in HIV-positive individuals. 60 61 62 For example, early immune exhaustion, comparable to that among people 40 years older, has been found among young HIV-positive individuals. 63 Immunosuppression and inflammation is associated with non-AIDS-defining cancers (NADCs) and whilst it appears that HIV-infection does contribute to the onset of NADC’s, HIV infection is thought to facilitate, rather than directly cause, their development. 64 65 66 67

  • Antiretroviral treatment. It is unclear whether antiretroviral treatment is linked to non-AIDS-defining cancers. 68 69 70 71 For example, some studies have suggested a link between some antiretroviral therapy drugs and the development of Hodgkin’s lymphoma. 72

However, the main evident effect of antiretroviral treatment, is that HIV-positive individuals now live longer and it is widely acknowledged that ageing itself is a risk factor for cancer. 73 74 Therefore, cancers that are typically reported among the ageing HIV-negative population are increasingly reported among HIV-positive individuals. 75 76 

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